Invasive Mold Infections After Chimeric Antigen Receptor–Modified T-Cell Therapy: A Case Series, Review of the Literature, and Implications for Prophylaxis - Haidar, Ghady; Dorritie, Kathleen; Farah, Rafic; Bogdanovich, Tatiana; Nguyen, M Hong; Samanta, Palash (Clinical Infectious Diseases, 2020)
Data on invasive mold infections (IMIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. We describe 2 patients with post–CAR-T-cell IMI (Fusarium, Mucorales) and review the published literature. We propose strategies to prevent IMIs in patients, based on the IMI rate and presence of neutropenia or steroid use.

Novel treatments for progressive multifocal leukoencephalopathy - Bennett, Karina M; Fernandes, Peter M (British Journal of Hospital Medicine, 2020)
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the central nervous system caused by JC virus that occurs in those with impaired immune systems. Existing treatment options are ineffective or unproven. This article reviews recent research into novel therapies: 1) immune checkpoint blocking antibodies (nivolumab and pembrolizumab); 2) allogenic BK virus-specific T cell treatment and 3) filgrastim. Results for these therapies in small clinical trials are promising, but further research is required to assess efficacy fully.

Multidisciplinary Tool Kit for Febrile Neutropenia: Stewardship Guidelines, Staphylococcus aureus Epidemiology, and Antibiotic Use Ratios - Bartash, Rachel; Cowman, Kelsie; Szymczak, Wendy; Guo, Yi; Ostrowsky, Belinda; Binder, Adam; Sheridan, Carol; Levi, Michael; Gialanella, Philip; Nori, Priya (JCO oncology practice, 2020)
PURPOSE: Inappropriate vancomycin for febrile neutropenia (FN) is an ideal antimicrobial stewardship target. To improve vancomycin prescribing, we instituted a multifaceted intervention, including an educational guideline with audit for compliance; an antibiotic use audit; and an assessment of local burden of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. MATERIALS AND METHODS: We conducted a quasi-experimental pre-post intervention review of vancomycin initiation for FN on a 32-bed hematology/oncology unit. A retrospective chart review was conducted from November 2015 to May 2016 (preintervention period). In January 2017, we implemented an institutional FN guideline emphasizing criteria for appropriate use. Vancomycin audit was conducted from February 2017 to October 2017 (postintervention period). The primary outcome was appropriateness of vancomycin initiation. We then compared average antibiotic use (days of therapy per 1,000 patient days) for vancomycin and cefepime before and after intervention. Finally, unit-wide MRSA screening cultures were obtained upon admission and bimonthly for 6 weeks (October 2, 2017, to November 9, 2017). Screened patients were followed for 12 months for clinical MRSA infection. RESULTS: Forty-three (49%) of 88 preintervention patients were started on empiric vancomycin appropriately, compared with 59 (66%) of 90 postintervention patients (P = .02). There was a significant decrease in vancomycin use after intervention. Six (7.1%) of 85 patients screened positive for MRSA colonization. During the 12-month follow-up, no colonized patients developed clinical MRSA infections (positive predictive value, 0.0%). Of the 79 noncolonized patients, 2 developed a clinically significant infection (negative predictive value, 97.5%). CONCLUSION: Guideline-focused education can improve vancomycin appropriateness in FN and should be bundled with education and feedback about local MRSA epidemiology and antibiotic use rates for maximal stewardship impact.
Keywords: Anti-Bacterial Agents; Febrile Neutropenia; Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Staphylococcus aureus

Food Safety For Older Adults and People With Cancer, Diabetes, HIV/AIDS, Organ Transplants, and Auto-Immune Diseases - FDA (2020)

Seguridad de los alimentos en adultos mayores, y personas con cáncer, diabetes, VIH/SIDA, trasplante de órganos y enfermedades autoinmunes - FDA (2020)

Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies - Davis, Joshua S.; Ferreira, David; Paige, Emma; Gedye, Craig; Boyle, Michael (Clinical Microbiology Reviews, 2020)
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. , SUMMARY The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.

Infectious Complications of Immune Checkpoint Inhibitors - Abers, Michael S.; Lionakis, Michail S. (Infectious Disease Clinics, 2020)
The clearance of both tumors and microbes depends on highly coordinated immune responses that are sufficiently potent to kill malignant or microbial cells while avoiding immunopathology from an overly exuberant inflammatory response. A molecular understanding of the immune pathways that regulate these responses paved the way for the development of checkpoint inhibitors (CPIs) as a therapeutic strategy to boost endogenous antitumor immunity. CPIs have demonstrated survival benefits across a wide spectrum of cancers. While infectious complications of CPIs are uncommon, immune-related adverse events occur frequently and often require immunosuppressive therapies that increase the risk of infection.

Infectious Risks Associated with Biologics Targeting Janus Kinase-Signal Transducer and Activator of Transcription Signaling and Complement Pathway for Inflammatory Diseases - Benamu, Esther (Infectious Disease Clinics, 2020)
The recognition of the role of complement and Janus kinase (JAK)–dependent cytokines in the pathogenesis of inflammatory and immune-mediated disorders has revolutionized the treatment of a myriad of rheumatological and inflammatory diseases. C5 inhibitors and Janus kinase inhibitors have emerged as attractive therapeutic options. Because of the blockage of immune pathways, these targeted therapies carry an increased risk of infection. This article reviews the mechanism of action and the approved and off-label indications of the agents with most clinical experience within this drug classes. It discusses the associated risks of infection, proposing screening, prevention, and risk mitigation strategies.

Mycobacterial Infections Potentiated by Biologics - Calabrese, Cassandra; Winthrop, Kevin L. (Infectious Disease Clinics, 2020)
Biologic therapies have revolutionized the treatment of immune-mediated inflammatory diseases but are associated with an increased risk of serious and opportunistic infections, including tuberculosis and nontuberculous mycobacterial disease. Despite this increased risk, the overall risk-benefit ratio remains favorable with appropriate screening and risk assessment. Further population-based studies are needed to establish the risk of tuberculosis and nontuberculous mycobacterial disease with the new biologics. This article highlights the incidence and drug-specific risk of tuberculous and nontuberculous mycobacterial infection in the setting of biologics, screening and prevention, and treatment of latent tuberculosis in this setting.

Fungal Infections Potentiated by Biologics - Davis, Matthew R.; Thompson, George R.; Patterson, Thomas F. (Infectious Disease Clinics, 2020)
Biologic therapies including monoclonal antibodies, tyrosine kinase inhibitors, and other agents represent a notable expansion in the pharmacotherapy armamentarium in treatment of a variety of diseases. Many of these therapies possess direct or indirect immunosuppressive and immunomodulatory effects, which have been associated with bacterial, viral, and fungal opportunistic infections. Careful screening of baseline risk factors before initiation, targeted preventive measures, and vigilant monitoring while on active biologic therapy mitigate these risks as use of biologics becomes more commonplace. This review compiles reported evidence of fungal infections associated with these agents with a focus on the tumor necrosis factor-α inhibitor class.

Direct T-cell Inhibition and Agents Targeting T-cell Migration and Chemotaxis - Fernández-Ruiz, Mario; Aguado, José María (Infectious Disease Clinics, 2020)
Lymphocyte depletion and blockade of T-cell activation and trafficking serve as therapeutic strategies for an enlarging number of immune-mediated diseases and malignancies. This review summarizes the infection risks associated to monoclonal antibodies that bind to the α chain of the interleukin-2 receptor, the cell surface glycoprotein CD52, and members of α4- and β2-integrin families acting as cell-adhesion molecules. An outline of the mechanisms of action, approved indications and off-label uses, expected impact on the host immune response, and available clinical evidence is provided for each of these agents.

Herpesvirus Infections Potentiated by Biologics - Ho, Dora Y.; Enriquez, Kyle; Multani, Ashrit (Infectious Disease Clinics, 2020)
Herpesviruses such as herpes simplex virus (HSV) type 1 and 2, varicella-zoster virus (VZV), and cytomegalovirus (CMV) maintain lifelong latency in the host after primary infection and can reactivate periodically either as asymptomatic viral shedding or as clinical disease. Immunosuppression, including biologic therapy, may increase frequency and severity of herpesvirus reactivation and infection. Licensed biologics are reviewed regarding their risks of potentiating HSV, VZV, and CMV reactivation and infection. Approaches to prophylaxis against HSV, VZV, and CMV infection or reactivation are discussed.

Vaccinations and Biologics - Hsiao, Betty; Khan, Aisha; Kang, Insoo (Infectious Disease Clinics, 2020)
The emergence of biologics has revolutionized the way physicians treat many autoimmune inflammatory conditions. Although biologics have become a vital component of the treatment approach to many inflammatory diseases, these agents may potentially disrupt the natural immune response against pathogens, thereby increasing the risk for infections. Some infections may be preventable or have a lessened risk through appropriate vaccinations; thus, vaccination history should be taken carefully in preparation for biologics and updated annually to maximize benefits while minimizing adverse effects. The objective of this review is to summarize recent articles, including guidelines, published that address vaccinations among patients on biologics.

Infectious Complications of Tyrosine Kinase Inhibitors in Hematological Malignancies - Kin, Andrew; Schiffer, Charles A. (Infectious Disease Clinics, 2020)
Tyrosine kinase inhibitors represent the standard of care for several diseases and drug targets in hematologic malignancies. Infectious complications vary by disease status and prior therapy, but overall incidence of infections generally is low. In chronic diseases, such as chronic myeloid leukemia and chronic lymphocytic leukemia, patients can remain on tyrosine kinase inhibitor therapy for many years, with few infectious complications from therapy. Bruton tyrosine kinase inhibitors overall are well tolerated in lymphoproliferative disorders, with long-term follow-up of many years in patients with chronic lymphocytic leukemia. Although opportunistic infections have been reported, they are uncommon and routine prophylaxis is not recommended.

Infectious Implications of Interleukin-1, Interleukin-6, and T Helper Type 2 Inhibition - Liu, Anne Y. (Infectious Disease Clinics, 2020)
Targeting interleukins that drive innate inflammation has expanded treatments of autoinflammatory and autoimmune disorders. Interleukin (IL)-1 inhibition has proven useful for monogenic autoinflammatory syndromes, and IL-6 inhibition for autoimmune arthritides. Biological therapies impeding these pathways impair detection and containment of pathogens, particularly invasive bacteria, reflecting the importance of IL-1 and IL-6 in communicating danger throughout the immune system. Biologics targeting T helper type 2 inflammation are used to treat specific allergic, atopic, and eosinophilic diseases. They may impair protections against local herpesvirus reactivations while augmenting antiviral responses to respiratory viruses. Their risks with helminth exposures have yet to be defined.

JC Polyomavirus Infection Potentiated by Biologics - Multani, Ashrit; Ho, Dora Y. (Infectious Disease Clinics, 2020)
The risk of JC polyomavirus encephalopathy varies among biologic classes and among agents within the same class. Of currently used biologics, the highest risk is seen with natalizumab followed by rituximab. Multiple other agents have also been implicated. Drug-specific causality is difficult to establish because many patients receive multiple immunomodulatory medications concomitantly or sequentially, and have other immunocompromising factors related to their underlying disease. As use of biologic therapies continues to expand, further research is needed into pathogenesis, treatment, and prevention of JC polyomavirus encephalopathy such that risk for its development is better understood and mitigated, if not eliminated altogether.

Hepatitis B Virus Reactivation Potentiated by Biologics - Ogawa, Eiichi; Wei, Mike T.; Nguyen, Mindie H. (Infectious Disease Clinics, 2020)
Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic therapies are required. This review provides the different classes of biologics associated with HBV reactivation, stratifies the various reactivation risk levels by HBV status and biologic agent, and discusses management strategies.

Epidermal Growth Factor Receptor Inhibitors and Other Tyrosine Kinase Inhibitors for Solid Tumors - Ruiz-Camps, Isabel; Aguilar-Company, Juan (Infectious Disease Clinics, 2020)
This article analyzes the risk of infection associated with small molecule kinase inhibitors used to treat solid organ malignancies and establishes specific recommendations. Most of these drugs are orally administered and have the ability to inhibit distinct kinases, which play a major role in cancer initiation and progression. Although the true extent of adverse events is not yet known, risk of infection does not seem to be a major problem with these drugs. Because of the limited clinical experience and the constant evolution of targeted therapies, recommendations may evolve in the near future.

Risk of Serious Infection Associated with Agents that Target T-Cell Activation and Interleukin-17 and Interleukin-23 Cytokines - Shoor, Stanford (Infectious Disease Clinics, 2020)
Co-stimulatory T-cell inhibitors are used in the treatment of rheumatoid arthritis and to prevent rejection of renal transplants. Inhibitors of the intereukin (IL-17) cytokine are indicated for psoriasis, psoriatic arthritis and ankylosing spondylitis and anti- IL-23 drugs for psoriasis. Serious infections occur in 4.2% to 25.0% of co-stimulatory inhibitors and 1.0% to 2.0% with IL-17 or IL-23 inhibitors. Underlying disease, steroid dose greater than 7.5 to 10.0 mg, and comorbidities influence risk in individual patients. Opportunistic infections or reactivation of tuberculosis are rare.

Donor-Derived Transmission of Cryptococcus gattii sensu lato in Kidney Transplant Recipients - Santos, Daniel W.C.L.; Hagen, Ferry; Meis, Jacques F.; Cristelli, Marina P.; Viana, Laila A.; Bernardi, Fabiola D.C.; Tedesco-Silva, Hélio; Medina-Pestana, José O.; Colombo, Arnaldo L. (Emerging Infectious Diseases, 2020)
We describe cases of donor-derived transmission of Cryptococcus deuterogattii in 2 kidney transplant recipients in Brazil and published information on other cases. Prompt reduction of immunosuppression and initiation of antifungal therapy was required to successfully control the fungal infections and preserve engraftment.

Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients - Samanta, Palash; Clancy, Cornelius J; Marini, Rachel V; Rivosecchi, Ryan M; McCreary, Erin K; Shields, Ryan K; Falcione, Bonnie A; Viehman, Alex; Sacha, Lauren; Kwak, Eun Jeong; Silveira, Fernanda P; Sanchez, Pablo G; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2020)
Isavuconazole was as effective as and better tolerated than voriconazole in preventing invasive fungal infections (IFIs) after lung transplantation. Breakthrough IFIs occurred in 3% of patients receiving isavuconazole or voriconazole prophylaxis. IFIs were associated with increased mortality and longer hospitalizations.

Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists - Rybak, Michael J; Le, Jennifer; Lodise, Thomas P; Levine, Donald P; Bradley, John S; Liu, Catherine; Mueller, Bruce A; Pai, Manjunath P; Wong-Beringer, Annie; Rotschafer, John C; Rodvold, Keith A; Maples, Holly D; et al. (American Journal of Health-System Pharmacy, 2020)
T he first consensus guideline for therapeutic monitoring of vancomycin in adult patients was published in 2009. A committee representing 3 organizations (the American Society for Health-System Pharmacists [ASHP], Infectious Diseases Society of America [IDSA], and Society for Infectious Diseases Pharmacists [SIDP]) searched and reviewed all relevant peer-reviewed data on vancomycin as it related to in vitro and in vivo pharmacokinetic and pharmacodynamic (PK/PD) characteristics, including information on clinical efficacy, toxicity, and vancomycin resistance in relation to serum drug concentration and monitoring. The data were summarized, and specific dosing and monitoring recommendations were made. The primary recommendations consisted of eliminating routine monitoring of serum peak concentrations, emphasizing a ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC) of ≥400 as the primary PK/PD predictor of vancomycin activity, and promoting serum trough concentrations of 15 to 20 mg/L as a surrogate marker for the optimal vancomycin AUC/MIC if the MIC was ≤1 mg/L in patients with normal renal function. The guideline also recommended, albeit with limited data support, that actual body weight be used to determine the vancomycin dosage and loading doses for severe infections in patients who were seriously ill.1

Utilization of hepatitis C virus–infected organ donors in cardiothoracic transplantation: An ISHLT expert consensus statement - Aslam, Saima; Grossi, Paolo; Schlendorf, Kelly H.; Holm, Are M.; Woolley, Ann E.; Blumberg, Emily; Mehra, Mandeep R.; Aslam, Saima; Mehra, Mandeep R.; Blumberg, Emily; Grossi, Paolo; Holm, Are M.; et al. (The Journal of Heart and Lung Transplantation, 2020)
Keywords: HCV; HCV+ cardiothoracic transplant; HCV+ transplant; consensus; donor; hepatitis C virus

Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors - Singh, Nina; Winston, Drew J.; Razonable, Raymund R.; Lyon, G. Marshall; Silveira, Fernanda P.; Wagener, Marilyn M.; Stevens-Ayers, Terry; Edmison, Bradley; Boeckh, Michael; Limaye, Ajit P. (JAMA, 2020)
This randomized trial compares preemptive therapy vs antiviral prophylaxis with valganciclovir in cytomegalovirus (CMV)-seronegative liver transplant recipients with seropositive donors for the prevention of CMV disease.

Liver Transplantation in Patients with Pretransplant Aspergillus Colonization: Is It Safe To Proceed? - Amin, Arpit; Molina, Alfonso; Quach, Lisa; Ito, Takahiro; McMillan, Robert; DiNorcia, Joseph; Agopian, Vatche G.; Kaldas, Fady M.; Farmer, Douglas G.; Busuttil, Ronald W.; Winston, Drew J. (Transplantation, 2020)

Low-Dose TMP-SMX in the Treatment of Pneumocystis jirovecii Pneumonia: A Systematic Review and Meta-analysis - Butler-Laporte, Guillaume; Smyth, Elizabeth; Amar-Zifkin, Alexandre; Cheng, Matthew P; McDonald, Emily G; Lee, Todd C (Open Forum Infectious Diseases, 2020)
Background Pneumocystis jirovecii pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15–20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety profile. Methods We conducted a systematic search in the Medline, Embase, and Cochrane Library databases from inception through March 2019 for peer-reviewed studies reporting on reduced doses of TMP-SMX (15 mg/kg/d of trimethoprim or less) for the treatment of PJP. PRISMA, MOOSE, and Cochrane guidelines were followed. Gray literature was excluded. Results Ten studies were identified, and 6 were included in the meta-analysis. When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, –9% in favor of reduced dose; 95% confidence interval [CI], –27% to 8%). When compared with standard doses, reduced doses of TMP-SMX were associated with an 18% (95% CI, –31% to –5%) absolute risk reduction of grade ≥3 adverse events. Conclusions In this systematic review, treatment of PJP with doses of ≤10 mg/kg/d of trimethoprim was associated with similar rates of mortality when compared with standard doses and with significantly fewer treatment-emergent severe adverse events. Although limited by the observational nature of the studies included, this review provides the most current available evidence for the optimal dosing of TMP-SMX in the treatment of PJP.

Efficacy of Cerebrospinal Fluid Beta-d-Glucan Diagnostic Testing for Fungal Meningitis: a Systematic Review - Davis, Christian; Wheat, L. Joseph; Myint, Thein; Boulware, David R.; Bahr, Nathan C. (Journal of Clinical Microbiology, 2020)
Several case reports and cohort studies have examined the use of (1,3)-beta-d-glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta-d-glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta-d-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded., Several case reports and cohort studies have examined the use of (1,3)-beta-d-glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta-d-glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta-d-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded. A total of 939 records were examined via a PubMed search. One hundred eighteen records remained after duplicates were removed, and 104 records were excluded, as they did not examine cerebrospinal fluid, included animals, or focused on nonfungal infections. Fourteen studies were included in this systematic review. A variety of fungi, including species of Candida, Aspergillus, Exserohilum, Cryptococcus, Histoplasma, and Coccidioides, were studied, although most were case reports. Diagnostic accuracy was examined in 5 studies. Cerebrospinal fluid (CSF) (1,3)-beta-d-glucan measurement showed >95% sensitivity in the corticosteroid injection-related outbreak of Exserohilum rostratum. One study in Histoplasma meningitis found 53% (53/87) sensitivity and 87% (133/153) specificity, while another study of Cryptococcus meningitis found 89% (69/78) sensitivity and 85% (33/39) specificity. CSF (1,3)-beta-d-glucan testing may be useful, primarily as a nonspecific marker of fungal meningitis. Although the FDA black box warning states that Cryptococcus spp. do not make (1,3)-beta-d-glucan, the current evidence shows that (1,3)-beta-d-glucan is detectable in cryptococcal meningitis. Organism-specific testing should be used in conjunction with (1,3)-beta-d-glucan measurement.

Presentation of BK polyomavirus–associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation - Imlay, Hannah; Xie, Hu; Leisenring, Wendy M.; Duke, Elizabeth R.; Kimball, Louise E.; Huang, Meei-Li; Pergam, Steven A.; Hill, Joshua A.; Jerome, Keith R.; Milano, Filippo; Nichols, W. Garrett; Pang, Phillip S.; et al. (Blood Advances, 2020)
BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials.

COVID-19 Vaccines for People Who Are Moderately or Severely Immunocompromised - CDC (Centers for Disease Control and Prevention, 2020)
COVID-19 vaccines protect against COVID-19. Get safety info and more.

Vacunas contra el COVID-19 para personas con inmunodepresión moderada o grave - CDC (Centers for Disease Control and Prevention, 2020)
Las vacunas contra el COVID-19 protegen contra el COVID-19. Obtenga información de seguridad y más.

Revisiting Role of Vaccinations in Donors, Transplant Recipients, Immunocompromised Hosts, Travelers, and Household Contacts of Stem Cell Transplant Recipients - Majeed, Aneela; Harris, Zoey; Brucks, Eric; Hinchman, Alyssa; Farooqui, Arafat Ali; Tariq, Muhammad Junaid; Tamizhmani, Kavin; Riaz, Irbaz bin; McBride, Ali; Latif, Azka; Kapoor, Vikas; Iftikhar, Raheel; et al. (Biology of Blood and Marrow Transplantation, 2020)
Vaccination is an effective strategy to prevent infections in immunocompromised hematopoietic stem cell transplant recipients. Pretransplant vaccination of influenza, pneumococcus, Haemophilus influenza type b, diphtheria, tetanus, and hepatitis B, both in donors and transplant recipients, produces high antibody titers in patients compared with recipient vaccination only. Because transplant recipients are immunocompromised, live vaccines should be avoided with few exceptions. Transplant recipients should get inactive vaccinations when possible to prevent infection. This includes vaccination against influenza, pneumococcus, H. influenza type b, diphtheria, tetanus, pertussis, meningococcus, measles, mumps, rubella, polio, hepatitis A, human papillomavirus, and hepatitis B. Close contacts of transplant recipients can safely get vaccinations (inactive and few live vaccines) as per their need and schedule. Transplant recipients who wish to travel may need to get vaccinated against endemic diseases that are prevalent in such areas. There is paucity of data on the role of vaccinations for patients receiving novel immunotherapy such as bispecific antibodies and chimeric antigen receptor T cells despite data on prolonged B cell depletion and higher risk of opportunistic infections.
Keywords: Allogeneic; Autologous; Hematopoietic stem cell transplantation; Infection prophylaxis; Traveler; Vaccination

Hope on the Horizon: Novel Fungal Treatments in Development - Rauseo, Adriana M; Coler-Reilly, Ariella; Larson, Lindsey; Spec, Andrej (Open Forum Infectious Diseases, 2020)
The treatment of invasive fungal infections remains challenging due to limitations in currently available antifungal therapies including toxicity, interactions, restricted routes of administration, and drug resistance. This review focuses on novel therapies in clinical development, including drugs and a device. These drugs have novel mechanisms of action to overcome resistance, and some offer new formulations providing distinct advantages over current therapies to improve safety profiles and reduce interactions. Among agents that target the cell wall, 2 glucan synthesis inhibitors are discussed (rezafungin and ibrexafungerp), as well as fosmanogepix and nikkomycin Z. Agents that target the cell membrane include 3 fourth-generation azoles, oral encochleated amphotericin B, and aureobasidin A. Among agents with intracellular targets, we will review olorofim, VL-2397, T-2307, AR-12, and MGCD290. In addition, we will describe neurapheresis, a device used as adjunctive therapy for cryptococcosis. With a field full of novel treatments for fungal infections, the future looks promising.

Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial - Vink, Peter; Ramon Torrell, Josep Maria; Sanchez Fructuoso, Ana; Kim, Sung-Joo; Kim, Sang-il; Zaltzman, Jeff; Ortiz, Fernanda; Campistol Plana, Josep Maria; Fernandez Rodriguez, Ana Maria; Rebollo Rodrigo, Henar; Campins Marti, Magda; Perez, Rafael; et al. (Clinical Infectious Diseases, 2020)
The adjuvanted recombinant zoster vaccine was immunogenic in renal transplant recipients receiving daily immunosuppressive treatment. Humoral and cell-mediated

Hyperammonemia Post Lung Transplantation: A Review - Leger, Robert F; Silverman, Matthew S; Hauck, Ellen S; Guvakova, Ksenia D (Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, 2020)
Hyperammonemia is the pathological accumulation of ammonia in the blood, which can occur in many different clinical settings. Most commonly in adults, hyperammonemia occurs secondary to hepatic dysfunction; however, it is also known to be associated with other pathologies, surgeries, and medications. Although less common, hyperammonemia has been described as a rare, but consistent complication of solid organ transplantation. Lung transplantation is increasingly recognized as a unique risk factor for the development of this condition, which can pose grave health risks—including long-term neurological sequelae and even death. Recent clinical findings have suggested that patients receiving lung transplantations may experience postoperative hyperammonemia at rates as high as 4.1%. A wide array of etiologies has been attributed to this condition. A growing number of case studies and investigations suggest disseminated opportunistic infection with Ureaplasma or Mycoplasma species may drive this metabolic disturbance in lung transplant recipients. Regardless of the etiology, hyperammonemia presents a severe clinical problem with reported mortality rates as high as 75%. Typical treatment regimens are multimodal and focus on 3 main avenues of management: (1) the reduction of impact on the brain through the use of neuroprotective medications and decreasing cerebral edema, (2) augmentation of mechanisms for the elimination of ammonia from the blood via hemodialysis, and (3) the diminishment of processes producing predominantly using antibiotics. The aim of this review is to detail the pathophysiology of hyperammonemia in the setting of orthotopic lung transplantation and discuss methods of identifying and managing patients with this condition.
Keywords: Hyperammonemia; Mycoplasma hominis; Ureaplasma; ammonia; critical care; dialysis; lung transplantation

Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases - Crabb, David W.; Im, Gene Y.; Szabo, Gyongyi; Mellinger, Jessica L.; Lucey, Michael R. (Hepatology, 2020)
An abstract is unavailable.

Recent Increase in the Prevalence of Fluconazole-Non-susceptible Candida tropicalis Blood Isolates in Turkey: Clinical Implication of Azole-Non-susceptible and Fluconazole Tolerant Phenotypes and Genotyping - Arastehfar, Amir; Hilmioğlu-Polat, Süleyha; Daneshnia, Farnaz; Hafez, Ahmed; Salehi, Mohammadreza; Polat, Furkan; Yaşar, Melike; Arslan, Nazlı; Hoşbul, Tuğrul; Ünal, Nevzat; Metin, Dilek Yeşim; Gürcan, Şaban; et al. (Frontiers in Microbiology, 2020)
Candida tropicalis is the fourth leading cause of candidemia in Turkey. Although C. tropicalis isolates from 1997 to 2017 were characterized as fully susceptible to antifungals, the increasing global prevalence of azole-non-susceptible (ANS) C. tropicalis and the association between high fluconazole tolerance (HFT) and fluconazole therapeutic failure (FTF) prompted us to re-evaluate azole susceptibility of C. tropicalis in Turkey. In this study, 161 C. tropicalis blood isolates from seven clinical centers were identified by ITS rDNA sequencing, genotyped by multilocus microsatellite typing, and tested for susceptibility to five azoles, two echinocandins, and amphotericin B (AMB); antifungal resistance mechanisms were assessed by sequencing of ERG11 and FKS1 genes. The results indicated that C. tropicalis isolates, which belonged to 125 genotypes grouped into 11 clusters, were fully susceptible to echinocandins and AMB; however, 18.6% of them had the ANS phenotype but only two carried the ANS-conferring mutation (Y132F). HFT was recorded in 52 isolates, 10 of which were also ANS. Large proportions of patients infected with ANS and HFT isolates (89 and 40.7%, respectively) showed FTF. Patients infected with azole-susceptible or ANS isolates did not differ in mortality, which, however, was significantly lower for those infected with HFT isolates (P = 0.007). There were significant differences in mortality (P = 0.02), ANS (P = 0.012), and HFT (P = 0.007) among genotype clusters. The alarming increase in the prevalence of C. tropicalis blood isolates with ANS and HFT in Turkey and the notable FTF rate should be a matter of public health concern.

Emerging Microbiology Diagnostics for Transplant Infections: On the Cusp of a Paradigm Shift - Azar, Marwan M.; Gaston, David C.; Kotton, Camille N.; Malinis, Maricar F. (Transplantation, 2020)
In light of the heightened risk for infection associated with solid organ and hematopoietic stem cell transplantation, rapid and accurate microbiology diagnostics are essential to the practice of transplant clinicians, including infectious diseases specialists. In the last decade, diagnostic microbiology has seen a shift toward culture-independent techniques including single-target and multiplexed molecular testing, mass-spectrometry, and magnetic resonance-based methods which have together greatly expanded the array of pathogens identified, increased processing speed and throughput, allowed for detection of resistance determinants, and ultimately improved the outcomes of infected transplant recipients. More recently, a newer generation of diagnostics with immense potential has emerged, including multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics, and gas chromatography mass spectrometry. Though these methods have some recognized drawbacks, many have already demonstrated improved sensitivity and a positive impact on clinical outcomes in transplant and immunocompromised patients.

Cytomegalovirus infection and allograft rejection among pediatric heart transplant recipients in the era of valganciclovir prophylaxis - Das, Bibhuti B.; Prusty, Bhupesh K.; Niu, Jianli; Sue, Paul K. (Pediatric Transplantation, 2020)
CMV infection remains a significant cause of morbidity among pediatric HTx recipients We explored the implications of CMV infection on post-transplant outcomes among CMV risk-stratified pediatric HTx recipients receiving VGC prophylaxis. Children who underwent HTx between January 2010 and October 2016 were stratified according to CMV risk at time of transplant and evaluated for evidence of post-transplant CMV infection, rejection, CAV, and graft loss. Among 97 children, 41 (42%) were considered HR or IR risk for CMV infection and received VGC prophylaxis. CMV DNAemia was observed in 34% of children, including 71% HR, 40% IR, and 18% LR individuals. Median time to CMV DNAemia following VGC prophylaxis was 32D among HR vs 277D in IR subjects (P = .042). No difference in overall graft loss was noted among groups, but CMV HR children had decreased rejection-free survival (3.5 years) compared to IR (6 years, P = .015) and LR children (8 years, P = .0003). CMV was noted on EMB in 13% of children but was not associated with increased CAV, rejection or graft loss. High-risk CMV status was associated with decreased time to CMV infection despite VGC prophylaxis, compared to IR, and decreased rejection-free survival times compared to both IR and LR recipients. Detection of CMV on EMB was not associated with increased rejection, CAV or graft loss. Additional studies are needed to explore the impact of CMV infection on rejection-free survival in HTx recipients.
Keywords: cardiac allograft vasculopathy; cytomegalovirus; pediatric heart transplantation; valganciclovir

Complications of Cryptosporidium infection after pediatric liver transplantation: Diarrhea, rejection, and biliary disease - Fischer, Ryan T.; Day, J. Christopher; Wasserkrug, Heather; Faseler, Megan; Kats, Alexander; Daniel, James F.; Slowik, Voytek; Andrews, Walter; Hendrickson, Richard J. (Pediatric Transplantation, 2020)
Background Cryptosporidium enteritis can be devastating in the immunocompromised host. In pediatric liver transplant recipients, infection may be complicated by prolonged carriage of the parasite, rejection, and biliary tree damage and fibrosis. Herein, we report on six patients and their long-term outcomes following cryptosporidiosis. Methods We reviewed all cases of cryptosporidiosis in a pediatric liver transplant population over a 17-year period at a single center. Six patients with infection were identified, and their outcomes were analyzed. Results Infection was associated with significant diarrhea and dehydration in all cases, and led to hospitalization in one-half of patients. Four of the six patients developed biopsy-proven rejection following infection, with three of those patients developing rejection that was recalcitrant to intravenous steroid treatment. Additionally, three patients developed biliary tree abnormalities with similarity to sclerosing cholangitis. In one patient, those biliary changes led to repeated need for biliary drain placement and advancing fibrotic liver allograft changes. Conclusions Cryptosporidiosis in pediatric liver transplant recipients may lead to significant complications, including recalcitrant episodes of rejection and detrimental biliary tree changes. We advocate for increased awareness of this cause of diarrheal disease and the allograft injuries that may accompany infection.
Keywords: Cryptosporidium; liver transplant; pediatrics; rejection

Higher risk of urinary tract infections in renal transplant recipients receiving pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia prophylaxis - Fu, Whitney; Barahona, Maria; Harkness, Taylor; Cohen, Elizabeth; Reardon, David; Yoo, Peter S. (Clinical Transplantation, 2020)
Urinary tract infection (UTI) is one of the most common infectious complications among renal transplant patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is routinely used as first-line prophylaxis against Pneumocystis pneumonia (PCP) and other opportunistic infections including UTI. Aerosolized pentamidine is an alternate agent used for PCP prophylaxis; however, it does not provide coverage against uropathogens. This is a retrospective study of 81 renal transplant recipients who received TMP-SMX or aerosolized pentamidine for PCP prophylaxis at our center over 1 year. Survival analysis demonstrated increased cumulative incidence of UTI among patients receiving pentamidine for PCP prophylaxis compared to those receiving TMP-SMX (log-rank test P < .001). Univariate and multivariate Cox proportional hazard regression model showed pentamidine prophylaxis (HR 3.740; 95% CI 1.745-8.016; P = .001) and female sex (HR 4.025; 95% CI 1.770-9.154; P = .001) to independently increase UTI risk. Age, induction agent, graft type, diabetes, and delayed graft function (DGF) were not associated with increased risk. This study concludes that the use of pentamidine for PCP prophylaxis compared to TMP-SMX is associated with increased risk of UTI. Secondary UTI prophylaxis may be considered for patients who are unable to tolerate TMP-SMX and who have other risk factors for UTI; however, the efficacy of this has not been studied.
Keywords: Pneumocystis pneumonia; opportunistic infection prophylaxis; pentamidine; renal transplant; trimethoprim-sulfamethoxazole; urinary tract infection

Long-lasting cluster of nosocomial pneumonia with a single Pneumocystis jirovecii genotype involving different organ allograft recipients - Hosseini‐Moghaddam, Seyed M.; Dufresne, Philippe J.; Gutierrez, Elaine Hunter; Dufresne, Simon F.; House, Andrew A.; Humar, Atul; Kumar, Deepali; Jevnikar, Anthony M. (Clinical Transplantation, 2020)
Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non-SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non-SOT (ie, 7 HIV-infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and outcome of PCP in SOT and non-SOT patients. Post-transplant PCP was frequently an acute-onset disease (90% vs. 18.2%, p = .01) requiring ICU admission (70% vs. 20%, p = .03) and hemodialysis (60% vs. 0, p = .003). Mortality was more frequent in SOT patients (40% vs. 18.1%, p = .36). Multilocus sequence typing (MLST) demonstrated circulation of a single genotype of P. jirovecii among SOT patients. However, 8 different genotypes were detected from non-SOT patients. Reinstitution of prophylaxis successfully controlled post-transplant cluster until end of observation period in October 2019. No transmission was detected from non-SOT patients to SOT recipients. Detection of a single P. jirovecii genotype from all SOT recipients highlights the likelihood of nosocomial transmission. No source control method is recommended by current guidelines. Improvement of preventive strategies is required.
Keywords: Pneumocystis jirovecii; pneumocystis pneumonia; solid organ transplantation

Incidence and outcomes of invasive fungal infection among solid organ transplant recipients: A population-based cohort study - Hosseini-Moghaddam, Seyed M.; Ouédraogo, Alexandra; Naylor, Kyla L.; Bota, Sarah E.; Husain, Shahid; Nash, Danielle M.; Paterson, J. Michael (Transplant Infectious Disease, 2020)
Background Invasive fungal infection (IFI) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long-term probability of post-transplant IFI is poorly understood. Methods We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, to determine the incidence rate; 1-, 5-, and 10-year cumulative probabilities of IFI; and post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also determined post-IFI, death-censored renal allograft failure. Results We included 9326 SOT recipients (median follow-up: 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person-years. The 1-year cumulative probability of IFI was 7.4% for lung, 5.4% for heart, 1.8% for liver, 1.2% for kidney-pancreas, and 1.1% for kidney-only allograft recipients. Lung transplant recipients had the highest incidence rate and 10-year probability of IFI: 43.0 per 1000 person-years and 26.4%, respectively. The 1-year all-cause mortality rate after IFI was 34.3%. IFI significantly increased the risk of mortality in SOT recipients over the entire follow-up period (hazard ratio: 6.50, 95% CI: 5.69-7.42). The 1-year probability of death-censored renal allograft failure after IFI was 9.8%. Conclusion Long-term cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1-year all-cause mortality.
Keywords: Invasive fungal infection; mycoses; solid organ transplantation

Impact of valganciclovir prophylaxis duration on cytomegalovirus disease in high-risk donor seropositive/recipient seronegative heart transplant recipients - Imlay, Hannah; Carcoana, Allison O. Dumitriu; Fisher, Cynthia E.; Wong, Beatrice; Rakita, Robert M.; Fishbein, Daniel P.; Limaye, Ajit P. (Transplant Infectious Disease, 2020)
Background Few data support use of 6 over 3 months of antiviral prophylaxis for cytomegalovirus (CMV) disease prevention in donor seropositive/recipient seronegative (D+R−) heart transplant recipients (HTR). Methods We retrospectively assessed CMV disease and outcomes in 310 adult HTR between July 5, 2005, and December 30, 2016, at our center. Valganciclovir (VGCV) prophylaxis was given for 3-6 months in the D+R− group. Multivariable models evaluated risk factors for CMV disease in patients who received 3 vs 6 months (±1 month) of prophylaxis, with investigation of inverse probability weighting to correct for confounding variables. Results The incidence of CMV disease among all patients and the D+R− group was 8.7% (27/310) and 26.5% (22/83), respectively, and included syndrome in 22.2% (6/27) and end-organ involvement in 77.8% (21/27). In a multivariable model, 6 vs 3 months of antiviral prophylaxis was not associated with reduced risk for CMV disease (OR 2.28 [95% CI 0.66, 7.91], P = .19). CMV disease in D+R− HTR was associated with higher rates of hospitalization (87.5% [14/16] vs 6.3% [1/16], P < .001) and for a longer duration than in matched D+R− controls without disease. Conclusions Cytomegalovirus disease remains a major cause of morbidity in D+R− HTR. In contrast to documented benefit in D+R− lung and kidney recipients, VGCV duration of 6 months was not associated with a lower incidence of CMV disease in D+R− HTR compared to 3-month duration and should be reconsidered in this patient population.
Keywords: antiviral prophylaxis; cytomegalovirus; heart transplantation

A community divided: Post-transplant live vaccine practices among Society of Pediatric Liver Transplantation (SPLIT) centers - Kemme, Sarah; Sundaram, Shikha S.; Curtis, Donna J.; Lobritto, Steven; Mohammad, Saeed; Feldman, Amy G. (Pediatric Transplantation, 2020)
Background Historically, the IDSA and the AST have recommended that live vaccines not be administered post-transplant due to concern for induction of vaccine-strain disease in immunocompromised hosts. However, recent prospective studies and revised AST guidelines published in April 2019 suggest that in the current era of immunosuppression minimization, live vaccines may be safely administered to select transplant recipients with resulting immunoprotection. The goal of this study was to assess current post-transplant live vaccine practices at individual pediatric liver transplant centers following the updated AST guidelines. Methods A six-item email survey detailing center-specific post-transplant live vaccine practices followed by up to three response-specific questions were distributed between July 2019 and May 2020 to a representative from each center participating in the SPLIT consortium. Results The overall survey response rate was 93% (41/44 centers). Only 29% (12/41) of centers offer live vaccines post-transplant; each of these 12 centers uses different eligibility criteria for live vaccines. There was no difference between large (ten or more transplants per year) and small (less than ten transplants per year) centers in likelihood to offer live vaccines post-transplant. The main reasons for a center not offering post-transplant live vaccines were safety concerns and inability to reach group consensus. Conclusions The majority of pediatric liver transplant centers are reluctant to offer live vaccines post-transplant despite the updated AST guidelines. Prospective multicenter studies are needed to confirm safety and immunogenicity of live vaccines post-transplant.
Keywords: immunizations; live vaccinations; measles; mumps; varicella

Strongyloides: Emerging Challenges and Prevention - La Hoz, Ricardo M.; Puing, Alfredo G. (Emerging Transplant Infections, 2020)

Hepatitis A Infections in Transplant - Lane, Rebekah J. (Emerging Transplant Infections, 2020)
Hepatitis A (HAV) is vaccine-preventable disease with an ongoing burden of disease nationally and worldwide. It is caused by a non-enveloped RNA virus with predominantly fecal-oral spread. It does not cause chronic disease and symptomatic infection increases with age. Fulminant disease and death are more common in the elderly and comorbid, particularly those with underlying chronic liver disease. Immunity to HAV infection occurs after infection or vaccination, with antibody levels indicating seroconversion. The additional role of cell-mediated immunity below this threshold is unclear in healthy hosts but even less deﬁned in those with abnormal immune systems or receiving immunosuppression after transplantation.

Ophthalmic Infections in Transplant - Lemieux, Jacob E.; Sobrin, Lucia; Barshak, Miriam B. (Emerging Transplant Infections, 2020)

Real-life food-safety behavior and incidence of foodborne infections in solid organ transplant recipients - Lindup, Matti; van den Bogaart, Lorena; Golshayan, Déla; Aubert, John-David; Vionnet, Julien; Regamey, Julien; Pascual, Manuel; Manuel, Oriol; Mombelli, Matteo (American Journal of Transplantation, 2020)
Food-safety measures are recommended in solid organ transplant (SOT) recipients. However, the actual adherence of patients in a real-life setting and the impact on the incidence of foodborne infections remain largely unexplored. We performed a survey among SOT recipients followed at our institution, aiming to evaluate their food-safety behavior. We assessed the incidence of microbiologically proven foodborne infections by chart review. One hundred ninety-seven SOT recipients (kidney = 117, lung = 35, liver = 29, and heart = 16) participated in the survey. Overall, 17.7% of the participants observed all food-safety recommendations (22.0% avoided food at risk of contamination while 67.9% applied hygiene recommendations). Patients within the first year after transplantation (odds ratio [OR] 5.42; P = .001) and females (OR 4.67; P = .001) followed food-safety recommendations more closely. Although the majority of SOT recipients felt concerned and actively sought information on food safety (68%-70%), only 27% were able to recognize all risks of foodborne infection in hypothetical scenarios. Incidence of proven foodborne infections was 17.9% (95% confidence interval 9.9%-30.9%) 5 years after transplantation. Importantly, foodborne infections occurred exclusively among patients not following food-safety recommendations. In summary, most SOT recipients eat foods that make them at risk of foodborne infections. Our results indicate that there is room for improvement in patient education, particularly later after transplantation, and reinforce current food-safety recommendations.
Keywords: clinical research/practice; education; infection and infectious agents; infectious disease; organ transplantation in general; patient education; patient safety; survey

Cytomegalovirus serologic matching in deceased donor kidney allocation optimizes high- and low-risk (D+R− and D−R−) profiles and does not adversely affect transplant rates - Lockridge, Joe; Roberts, Daniel; Olyaei, Ali; Noble, Brie N.; Langewisch, Eric; Rehman, Shehzad; Stack, Megan; Scott, David; Orloff, Susan; Shaut, Carley; Gardner, Brent; Bennett, William; et al. (American Journal of Transplantation, 2020)
Cytomegalovirus (CMV) is a major cause of infection-related morbidity and mortality in kidney transplantation. The most significant risk for developing CMV infection after transplant depends upon donor (D) and recipient (R) CMV serostatus. In 2012, our Organ Procurement Organization (OPO) began a novel pretransplant CMV prevention strategy via matching deceased kidney donors and recipients by CMV serostatus. Prior to the matching protocol, our distribution of seropositive and seronegative donors and recipients was similar to the United States at large. After the matching protocol, high-risk D+R− were reduced from 18.5% to 2.9%, whereas low-risk D−R− were increased from 13.5% to 24%. There was no adverse effect on transplant rates and no differential effect on waiting times for R+ vs R− after the protocol was implemented. This protocol could be implemented on a regional or national level to optimize low and high-risk CMV seroprofiles and potentially improve CMV-related outcomes in kidney transplantation.
Keywords: antibiotic prophylaxis; clinical research/practice; health services and outcomes research; infection and infectious agents – viral: Cytomegalovirus (CMV); infectious disease; kidney transplantation/nephrology; organ allocation; organ procurement and allocation; waitlist management

Transfusion-transmitted and community-acquired cytomegalovirus infection in seronegative solid organ transplant recipients receiving seronegative donor organs - Mabilangan, Curtis; Burton, Catherine; Nahirniak, Susan; O’Brien, Sheila; Preiksaitis, Jutta (American Journal of Transplantation, 2020)
Solid organ transplant (SOT) recipients who are cytomegalovirus (CMV) seronegative (R−) and receive seronegative donor (D−) organs have a small but currently unquantified risk of both transfusion-transmitted CMV (TT-CMV) and community-acquired CMV (CA-CMV). We retrospectively studied the incidence and clinical symptoms of TT-CMV (infection <1 year posttransplant) and CA-CMV (infection >1 year posttransplant) in a cohort of D−/R− adult and pediatric SOT recipients receiving leukoreduced blood products not screened for CMV seronegativity transplanted at our center between 2000 and 2011. CMV infection was defined as IgG seroconversion or detectable CMV antigenemia/DNAemia. Among 536 consecutive D−/R− recipients, 398 (81.8%) had adequate follow-up, and 231 (58%) received cellular blood products (total: 1626 red blood cell units, 470 platelet units) 30 days pretransplant to 90 days posttransplant. We observed no confirmed TT-CMV cases, but 14 CA-CMV cases (64% symptomatic) were seen. The estimated incidence rate of CA-CMV was higher in children (3.0/100 patient years) than adults (0.46/100 patient years, incident rate ratio of 6.52). The absence of TT-CMV over 11 years suggests neither seronegative blood products nor CMV DNA blood donor screening would provide significant incremental safety when blood is already leukoreduced. D−/R− SOT recipients, particularly children, have a significantly higher and ongoing risk of CA-CMV.
Keywords: clinical research/practice; infection and infectious agents – viral: cytomegalovirus (CMV); infectious disease; organ transplantation in general; transfusion

Candida auris Isolates Resistant to Three Classes of Antifungal Medications — New York, 2019 - Ostrowsky, Belinda (MMWR. Morbidity and Mortality Weekly Report, 2020)
Candida auris is a globally emerging yeast that causes outbreaks in health care settings and is often resistant to one or more classes of antifungal medications.

Methenamine hippurate may have particular benefit in preventing recurrent urinary tract infections in diabetic renal transplant recipients - Quintero Cardona, Orlando; Hemmige, Vagish S.; Puius, Yoram A. (Transplant Infectious Disease, 2020)
Keywords: diabetes; kidney transplant; methenamine; urinary tract infection

Conversion to belatacept maintenance immunosuppression in HIV-positive kidney transplant recipients - Santeusanio, Andrew; Bhansali, Arjun; Boccardo, Graciela De; Sehgal, Vinita; Delaney, Veronica; Florman, Sander; Shapiro, Ron (Clinical Transplantation, 2020)
There are only scattered case reports documenting belatacept use in HIV + kidney transplant recipients. We performed a retrospective review to describe short-term outcomes following conversion to belatacept in a cohort of HIV + patients. Patients were included if they were converted to belatacept between May 2015 and May 2019, had an HIV- donor, and received ≥4 doses of belatacept. All patients were treated with non-depleting induction and triple maintenance immunosuppression. Allograft and HIV-related outcomes were collected from the date of belatacept infusion until May 2020. Ten HIV + kidney transplant recipients were identified, who were converted to belatacept a median of 364 days post-transplant. At last follow-up (median 3.3 years), 8 patients remained on belatacept therapy, and all patients were alive with functioning allografts. Mean estimated glomerular filtration rates (eGFR) improved from 31.6 mL/min at baseline to 42.8 mL/min at 1 year (P = .03). Two patients developed acute rejection, with one necessitating conversion back to tacrolimus. All patients maintained undetectable HIV-1 viral loads at last follow-up. One patient each developed pneumocystis pneumonia and Kaposi sarcoma following conversion, which were responsive to standard medical therapy. In our cohort of stable HIV + kidney transplant recipients, conversion to belatacept was associated with excellent early patient and allograft survival and improved eGFR at 1 year.
Keywords: belatacept; human immunodeficiency virus; immunosuppressive agents; kidney transplantation; transplant rejection

Current state of kidney transplantation in patients with HIV, hepatitis C, and hepatitis B infection - Sawinski, Deirdre; Wong, Tiffany; Goral, Simin (Clinical Transplantation, 2020)
Human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common chronic viral infections in the end-stage kidney disease (ESKD) patient population that were once considered relative contraindications to kidney transplantation. In this review, we will summarize the current state of kidney transplantation in patients with HIV, HCV, and HBV, which is rapidly evolving. HIV+ patients enjoy excellent outcomes in the modern transplant era and may have new transplant opportunities with the use of HIV+ donors. Direct-acting antivirals for HCV have substantially changed the landscape of care for patients with HCV infection. HBV+ patients now have excellent patient and allograft survival with HBV therapy. Currently, kidney transplantation is a safe and appropriate treatment for the majority of ESKD patients with HIV, HCV, and HBV.
Keywords: HIV; hepatitis B; hepatitis C; kidney transplantation

Mycoplasma and Ureaplasma Infections in Transplantation: A Big Impact Despite the Lack of a Cell Wall - Schreiber, Peter W.; Müller, Nicolas (Emerging Transplant Infections, 2020)
In the general population, Mycoplasma spp. and Ureaplasma spp. are considered as pathogens with low virulence. Asymptomatic urogenital colonization with genital mycoplasmas is common. M. pneumoniae infections most frequently present as tracheobronchitis. In immunosuppressed individuals, a broad spectrum of invasive diseases has been attributed to these pathogens. After kidney transplantation and hematopoietic stem cell transplantation, Mycoplasma spp. and Ureaplasma spp. have been detected as causative pathogens in urogenital infections. Surgical site infections following solid organ transplantation are rarely caused by Mycoplasma spp. and Ureaplasma spp.. Recently, an association between hyperammonemia syndrome and genital mycoplasmas has been described after lung, kidney, and hematopoietic stem cell transplantation.

Frequency of asymptomatic and symptomatic respiratory virus detection in pediatric hematopoietic cell transplant patients - Schuster, Jennifer E.; Banerjee, Dithi; Ahmed, Ibrahim; Selvarangan, Rangaraj (Pediatric Transplantation, 2020)
Respiratory viral infections are common and can cause significant morbidity and mortality in pediatric patients undergoing hematopoietic cell transplantation (HCT). The prevalence of disease has been primarily identified from retrospective studies using standard-of-care specimens. The incidence of both asymptomatic respiratory viral detection and symptomatic respiratory viral detection in this high-risk population is not well described. We performed longitudinal, active, prospective surveillance in pediatric HCT patients. Subjects underwent weekly midturbinate swabs (MTSs) for the detection of 18 respiratory viruses and subtypes peri-HCT and 100 days post-HCT. Clinical data were obtained from the medical record. From September 2015 to February 2017, 24 children underwent 29 HCT, and 284 MTSs were collected. Forty-two (15%) specimens were virus-positive from 10 (42%) subjects. Specimens from children undergoing allogeneic HCT were more likely to have a virus detected (17% vs 8%, P = .04) compared with specimens from children undergoing autologous HCT. Sixteen (38%) detections were not associated with symptoms. Almost half (8/17) of the unique viral infections occurred during the HCT hospitalization after a negative specimen, suggesting nosocomial acquisition, and preceded detection from a clinical specimen. Rhinovirus, the most common virus detected, was the only virus detected in 33 (81%) virus-positive specimens; only 11 (33%) rhinovirus detections were asymptomatic. Asymptomatic detection of coronavirus and bocavirus occurred. Asymptomatic respiratory virus detection occurred in more than one-third of the children undergoing HCT. The acquisition of respiratory viruses during HCT hospitalization suggests nosocomial acquisition. Early detection of respiratory viruses during asymptomatic periods could have infection prevention and treatment implications.
Keywords: asymptomatic viral detection; hematopoietic cell transplant; respiratory viral infection; rhinovirus

Epstein-Barr viral load monitoring for diagnosing post-transplant lymphoproliferative disorder in pediatric liver transplant recipients - Seo, Euri; Kim, Joonil; Oh, Seak Hee; Kim, Kyung Mo; Kim, Dae Yeon; Lee, Jina (Pediatric Transplantation, 2020)
This study aimed to investigate the incidence of PTLD in pediatric liver transplant recipients and the risk factors for the development of PTLD. We also determined clinically useful quantitative EBV PCR parameters for aiding in the diagnosis of EBV-associated PTLD in the pediatric liver transplant recipients at our institute. We reviewed children < 18 years old who had undergone liver transplantations and quantitative analysis of whole blood EBV load at our institute from January 2006 to March 2015. A total of 142 liver transplant recipients were included, and their median age was 1.5 years. Clinically significant high-level EBV DNAemia ≥ 10 000 copies/mL at least twice was observed in 53.5% and PTLD occurred in 9.9%. Among PTLD group, graft failure and mortality rate were as high as 21.4% and 14.3%, respectively. Deceased donor, presence of high-level EBV DNAemia, and primary CMV infection following transplant were associated with an increased risk for PTLD in the multivariate analysis. The peak titer at 10 875 copies/mL could be used as a cutoff value with a sensitivity of 92.9% and a specificity of 37.9%; the rate of increase in EBV load suggested a sensitivity of 64.3% and a specificity of 70.9% at the cutoff value of 44 000 copies/mL/week. In conclusion, the incidence of PTLD following liver transplant in children was as high as 10%. PTLD is associated with significant morbidity and mortality. Close monitoring of EBV DNAemia is crucial for the early diagnosis and proper treatment of PTLD in pediatric liver transplant recipients.
Keywords: Epstein-Barr virus; pediatric liver transplantation; post-transplant lymphoproliferative disorders

Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020 - Sterling, Timothy R. (MMWR. Recommendations and Reports, 2020)
These updated 2020 latent tuberculosis infection treatment guidelines include the recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy

Candida auris outbreak involving liver transplant recipients in a surgical intensive care unit - Theodoropoulos, Nicole M.; Bolstorff, Barbara; Bozorgzadeh, Adel; Brandeburg, Christina; Cumming, Melissa; Daly, Jennifer S.; Ellison III, Richard T.; Forsberg, Kaitlin; Gade, Lalitha; Gibson, Laura; Greenough, Thomas; Litvintseva, Anastasia P.; et al. (American Journal of Transplantation, 2020)
Candida auris is a yeast that is difficult to eradicate and has caused outbreaks in health care facilities. We report a cluster of 5 patients in 1 intensive care unit who were colonized or infected in 2017. The initial 2 patients were recipients of liver transplants who had cultures that grew C auris within 3 days of each other in June 2017 (days 43 and 30 posttransplant). Subsequent screening cultures identified 2 additional patients with C auris colonization. Respiratory and urine cultures from a fifth patient yielded C auris. All isolates were fluconazole resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from New York/New Jersey strains, consistent with a separate introduction. However, no source or contact was found. Two of the 5 patients died. C auris infection likely contributed to 1 patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that although severe disease from C auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C auris to date.
Keywords: clinical research/practice; infection and infectious agents; infection and infectious agents – fungal; infectious disease

Pericardial effusion following hematopoietic stem cell transplantation in children: Incidence, risk factors, and outcomes - Tinianow, Alex; Gay, James C.; Bearl, David W.; Connelly, James A.; Godown, Justin; Kitko, Carrie L. (Pediatric Transplantation, 2020)
PCE is a complication of HSCT that has previously been described in small single-center studies. This study aimed to assess the frequency of, risk factors for, and outcomes of children with a PCE following HSCT across a large multi-center cohort. All patients ≤21 years undergoing first HSCT (1/2005-9/2015) were identified from the Pediatric Health Information System. ICD-9 codes were used to identify patients with a PCE during or following the transplant encounter. Multivariable modeling assessed risk factors for developing a PCE and assessed the impact of PCE on patient outcome. Of 10 455 included patients, 739 (7.1%) developed a PCE (median 69 days post-HSCT, interquartile range 33-165 days). PCE developed more commonly in allogeneic vs autologous HSCT recipients (9.1% vs 2.9%, P < .001). Among allogeneic HSCT recipients, independent risk factors for PCE included thrombotic microangiopathy (AHR 2.94, 95% CI 2.16-4.00), heart failure (AHR 2.07, 95% CI 1.61-2.66), PCE pre-HSCT (AHR 1.92, 95% CI 1.19-3.09), arrhythmia (AHR 1.76, 95% CI 1.44-2.16), graft-versus-host disease (AHR 1.31, 95% CI 1.05-1.62), female sex (AHR 1.28, 95% CI 1.07-1.52), and malignancy (AHR 1.28, 95% CI 1.02-1.60). Allogeneic HSCT patients with PCE demonstrated worse survival than those without PCE (5-year survival 50.8% vs 76.9%, P < .001). PCE was independently associated with mortality (AHR 1.96, 95% CI 1.62-2.37) following allogeneic HSCT and was not impacted by pericardial intervention. PCE occurs more commonly in patients following allogeneic (vs autologous) HSCT and is associated with inferior outcomes.
Keywords: bone marrow transplantation; complication; pericardial effusion; survival

Guide for clinical case management and infection prevention and control during a measles outbreak - World Health Organization (World Health Organization, 2020)
Keywords: Disease Outbreaks; Guideline; Infection Control; Measles

Evaluation of 10 years of parainfluenza virus, human metapneumovirus, and respiratory syncytial virus infections in lung transplant recipients - Zwart, Auke E. S. de; Riezebos‐Brilman, Annelies; Alffenaar, Jan-Willem C.; Heuvel, Edwin R. van den; Gan, Christiaan Tji; Bij, Wim van der; Kerstjens, Huib A. M.; Verschuuren, Erik A. M. (American Journal of Transplantation, 2020)
Respiratory tract infection with pneumoviruses (PVs) and paramyxoviruses (PMVs) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Ribavirin may be a treatment option but its effectiveness is unclear, especially with respect to infection severity. We retrospectively analyzed 10 years of PV/PMV infections in LTRs. The main end points were forced expiratory volume in 1 second (FEV1) at 3 and 6 months postinfection, expressed as a percentage of pre-infection FEV1 and incidence of new or progressed CLAD 6 months postinfection. A total of 139 infections were included: 88 severe infections (63%) (defined as >10% FEV1 loss at infection) and 51 mild infections (37%) (≤10% FEV1 loss). Overall postinfection CLAD incidence was 20%. Associations were estimated on postinfection FEV1 for ribavirin vs no ribavirin (+13.2% [95% CI: 7.79; 18.67]) and severe vs mild infection (−11.1% [95% CI: −14.76; −7.37]). Factors associated with CLAD incidence at 6 months were ribavirin treatment (odds ratio (OR [95% CI]) 0.24 [0.10; 0.59]), severe infection (OR [95% CI] 4.63 [1.66; 12.88]), and mycophenolate mofetil use (OR [95% CI] 0.38 [0.14; 0.97]). These data provide valuable information about the outcomes of lung transplant recipients with these infections and suggests possible associations of ribavirin use and infection severity with long-term outcomes. Well-designed prospective trials are needed to confirm these findings.
Keywords: antibiotic: antiviral; clinical research/practice; infection and infectious agents – viral; infectious disease; lung (allograft) function/dysfunction; lung transplantation/pulmonology

Third-Generation Sequencing in the Clinical Laboratory: Exploring the Advantages and Challenges of Nanopore Sequencing - Petersen, Lauren M.; Martin, Isabella W.; Moschetti, Wayne E.; Kershaw, Colleen M.; Tsongalis, Gregory J. (Journal of Clinical Microbiology, 2019)
Metagenomic sequencing for infectious disease diagnostics is an important tool that holds promise for use in the clinical laboratory. Challenges for implementation so far include high cost, the length of time to results, and the need for technical and bioinformatics expertise. However, the recent technological innovation of nanopore sequencing from Oxford Nanopore Technologies (ONT) has the potential to address these challenges., Metagenomic sequencing for infectious disease diagnostics is an important tool that holds promise for use in the clinical laboratory. Challenges for implementation so far include high cost, the length of time to results, and the need for technical and bioinformatics expertise. However, the recent technological innovation of nanopore sequencing from Oxford Nanopore Technologies (ONT) has the potential to address these challenges. ONT sequencing is an attractive platform for clinical laboratories to adopt due to its low cost, rapid turnaround time, and user-friendly bioinformatics pipelines. However, this method still faces the problem of base-calling accuracy compared to other platforms. This review highlights the general challenges of pathogen detection in clinical specimens by metagenomic sequencing, the advantages and disadvantages of the ONT platform, and how research to date supports the potential future use of nanopore sequencing in infectious disease diagnostics.

Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium - Cornely, Oliver A.; Alastruey-Izquierdo, Ana; Arenz, Dorothee; Chen, Sharon C. A.; Dannaoui, Eric; Hochhegger, Bruno; Hoenigl, Martin; Jensen, Henrik E.; Lagrou, Katrien; Lewis, Russell E.; Mellinghoff, Sibylle C.; Mer, Mervyn; et al. (The Lancet Infectious Diseases, 2019)
Summary Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.

Human herpesvirus 6 in transplant recipients: An update on diagnostic and treatment strategies - Hill, Joshua A. (Current opinion in infectious diseases, 2019)
Purpose of Review: This review article focuses on recent advances in the approach to the diagnosis and treatment of human herpesvirus 6B (HHV-6B) in hematopoietic cell and solid organ transplant recipients. Recent Findings: Over the past few years, key studies have broadened our understanding of best practices for the prevention and treatment of HHV-6B encephalitis after transplantation. Moreover, important data have been reported that support a potential role of HHV-6B reactivation in the development of acute graft-versus-host disease and lower respiratory tract disease in transplant recipients. Finally, increasing recognition of inherited chromosomally integrated HHV-6 (iciHHV-6) and an expanding array of diagnostic tools have increased our understanding of the potential for complications related to viral reactivation originating from iciHHV-6 in donor allografts and recipients. Summary: Recent advances in diagnostic tools, disease associations, and potential treatments for HHV-6B present abundant opportunities for improving our understanding and management of this complex virus in transplant recipients.

Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial - Kaye, Keith S; Rice, Louis B; Dane, Aaron L; Stus, Viktor; Sagan, Olexiy; Fedosiuk, Elena; Das, Anita F; Skarinsky, David; Eckburg, Paul B; Ellis-Grosse, Evelyn J (Clinical Infectious Diseases, 2019)
Background.  ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gramnegative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States. Methods.  Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days. Results.  Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: −0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19–21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient. Conclusions.  ZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections. Clinical Trial Registration. NCT02753946

Management of adults and children undergoing CAR t-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) - Yakoub-Agha, Ibrahim; Chabannon, Christian; Bader, Peter; Basak, Grzegorz W.; Bonig, Halvard; Ciceri, Fabio; Corbacioglu, Selim; Duarte, Rafael F.; Einsele, Hermann; Hudecek, Michael; Kersten, Marie José; Köhl, Ulrike; et al. (Haematologica, 2019)
Chimeric antigen receptor T-cells are a novel class of anti-cancer therapy in which autologous or allogeneic T-cells are engineered to express a chimeric antigen receptor targeting a membrane antigen. In Europe, Tisagenlecleucel (KymriahTM) is approved for the treatment of refractory/relapsed Acute Lymphoblastic Leukaemia in children and young adults as well as relapsed/refractory Diffuse Large B-cell Lymphoma; Axicabtagene ciloleucel (YescartaTM) is approved for the treatment of relapsed/refractory high-grade B-cell Lymphoma and Primary Mediastinal B-cell Lymphoma. Both agents are genetically engineered autologous T-cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of chimeric antigen receptor T-cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological patient support, long-term follow-up, post-authorisation safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline - Nahid, Payam; Mase, Sundari R.; Migliori, Giovanni Battista; Sotgiu, Giovanni; Bothamley, Graham H.; Brozek, Jan L.; Cattamanchi, Adithya; Cegielski, J. Peter; Chen, Lisa; Daley, Charles L.; Dalton, Tracy L.; Duarte, Raquel; et al. (American Journal of Respiratory and Critical Care Medicine, 2019)
Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial - Buonfrate, Dora; Salas-Coronas, Joaquin; Muñoz, José; Maruri, Begoña Trevino; Rodari, Paola; Castelli, Francesco; Zammarchi, Lorenzo; Bianchi, Leila; Gobbi, Federico; Cabezas-Fernández, Teresa; Requena-Mendez, Ana; Godbole, Gauri; et al. (The Lancet Infectious Diseases, 2019)
Summary Background Strongyloides stercoralis infection is a neglected condition that places people who are immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis. Methods Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 μg/kg or four doses of ivermectin 200 μg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment. Findings Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI −7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility. Interpretation Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis. Funding There was no funding source for this study.

Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation - Ward, Katherine N.; Hill, Joshua A.; Hubacek, Petr; Camara, Rafael de la; Crocchiolo, Roberto; Einsele, Hermann; Navarro, David; Robin, Christine; Cordonnier, Catherine; Ljungman, Per (Haematologica, 2019)
Of the two human herpesvirus 6 (HHV-6) species, human herpesvirus 6B (HHV-6B) encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematologic malignancies or post-transplant were prepared a decade ago but there have been no other guidelines since then despite significant advances in the understanding of HHV-6 encephalitis, its therapy, and other aspects of HHV-6 disease in this patient population. Revised guidelines prepared at the 2017 European Conference on Infections in Leukaemia covering diagnosis, preventative strategies and management of HHV-6 disease are now presented.

Cutaneous Mycobacterium Marinum Infection (Fish Tank Granuloma) in a Renal Transplant Recipient: Case Report and Literature Review - Assiri, Ahmad; Euvrard, Sylvie; Kanitakis, Jean; Assiri, Ahmad; Euvrard, Sylvie; Kanitakis, Jean (Cureus, 2019)
Atypical mycobacterioses are unusual infections of the skin and other organs caused by non-tuberculous mycobacteria. Fish tank granuloma and swimming pool granuloma are two forms of atypical mycobacterioses caused by Mycobacterium marinum. So far, only a few cases of these infections have been reported in organ transplant patients, and these usually are more severe when compared with atypical mycobacterioses in immunocompetent hosts. We report a kidney transplant patient with a rather mild form of atypical mycobacteriosis (fish tank granuloma) who responded well to treatment with doxycycline and will provide a review of all similar cases reported in the literature.

Reported β-Lactam and Other Antibiotic Allergies in Solid Organ and Hematopoietic Cell Transplant Recipients - Imlay, Hannah; Krantz, Elizabeth M; Stohs, Erica J; Lan, Kristine F; Zier, Jacqlynn; Kim, H Nina; Rakita, Robert M; Limaye, Ajit P; Wald, Anna; Pergam, Steven A; Liu, Catherine (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2019)
β-Lactam and other reported antibiotic allergies are common among hematopoietic cell and solid organ transplant recipients. Patients with reported β-lactam allergies have higher use of β-lactam alternative antibiotics following transplant.

Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli - Al-Tamimi, Mohammad; Abu-Raideh, Jumana; Albalawi, Hadeel; Shalabi, Marwan; Saleh, Saiel (Microbial Drug Resistance, 2019)
Background: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing worldwide. The drugs of choice for treatment of ESBLs are parenteral carbapenems. The aim of this study was to evaluate the in vitro and in vivo efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. Methods: A total of 150 ESBL-EC samples were collected over 1 year from two referral centers. Synergistic studies of cephalosporins and amoxicillin/clavulanate were performed in vitro using disk approximation and disk replacement methods. Combination treatment was assessed in vivo on 20 ESBL-EC urinary tract infection (UTI) patients. Results: ESBL-EC isolates were confirmed in 150 patients with a mean age of 46.67 years, 75.2% of them being women. Antibiotic susceptibility testing of isolates indicated high resistance rate to oral antibiotics. The frequency of positive synergy and mean distance of synergy between cephalosporins and amoxicillin/clavulanate was significantly higher with cefotaxime and cefixime compared with cefpodoxime, cefdinir, and ceftazidime using disk approximation and disk replacement methods (p < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (p < 0.0005). Cefixime and amoxicillin/clavulanate synergy was not affected by age, gender, hospital, department, sample type, or bacterial load. Eighteen of 20 ESBL-EC-positive UTI patients had a positive in vitro synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. Conclusions: Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. In vitro synergistic testing is simple and predictive of successful treatment.
Keywords: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefixime; Cefotaxime; Cephalosporins; E. coli; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Urinary Tract Infections; Young Adult; beta-Lactamases; cefixime; clavulanic acid; extended-spectrum beta-lactamase (ESBL); synergy

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C Virus Infection in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2018 Clinical Practice Guideline - Gordon, Craig E.; Berenguer, Marina C.; Doss, Wahid; Fabrizi, Fabrizio; Izopet, Jacques; Jha, Vivekanand; Kamar, Nassim; Kasiske, Bertram L.; Lai, Ching-Lung; Morales, José M.; Patel, Priti R.; Pol, Stanislas; et al. (Annals of Internal Medicine, 2019)

Role of Gallium-SPECT-CT in the Management of Patients With Ventricular Assist Device-Specific Percutaneous Driveline Infection - Kimura, Yuki; Seguchi, Osamu; Mochizuki, Hiroki; Iwasaki, Keiichiro; Toda, Koichi; Kumai, Yuto; Kuroda, Kensuke; Nakajima, Seiko; Tateishi, Emi; Watanabe, Takuya; Matsumoto, Yorihiko; Fukushima, Satsuki; et al. (Journal of Cardiac Failure, 2019)
Background Percutaneous driveline infection is a major complication of left ventricular assist device (LVAD). This study evaluated the role of gallium-67 single-photon emission computed tomography (Ga-SPECT)-CT in LVAD-specific percutaneous driveline infection. Methods Thirty-six patients with implantable continuous-flow LVAD, who underwent Ga-SPECT-CT to evaluate percutaneous driveline infections, were enrolled and divided into uptake and no-uptake groups based on tracer concentration uptake on Ga-SPECT-CT. Primary outcomes were surgical intervention and readmission for driveline infection. Results Twenty-two patients had uptake on Ga-SPECT-CT. No significant differences were noted in patient characteristics, wound appearance, or laboratory results. The prevalence of positive skin culture at the driveline exit site (DLES), and usage and duration of antibiotics did not differ. However, the uptake group had higher 1-year event rates (surgical intervention: 39% vs 0%, P = .019; readmission: 74% vs 6.9%, P = .0016). In addition to positive skin culture at DLES and short duration of antibiotic therapy, uptake on Ga-SPECT-CT was a risk factor for surgical intervention (odds ratio 9.00; P = .018) and readmission (odds ratio 7.86; P = .0051). Conclusions Ga-SPECT-CT could be one of the clinical modalities for guiding the treatment of driveline infection in patients with a LVAD.
Keywords: Driveline infection; SPECT-CT; gallium scintigraphy; ventricular assist device

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America - Metlay, Joshua P.; Waterer, Grant W.; Long, Ann C.; Anzueto, Antonio; Brozek, Jan; Crothers, Kristina; Cooley, Laura A.; Dean, Nathan C.; Fine, Michael J.; Flanders, Scott A.; Griffin, Marie R.; Metersky, Mark L.; et al. (American Journal of Respiratory and Critical Care Medicine, 2019)
Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
Keywords: community-acquired pneumonia; pneumonia; patient management

MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis - Spec, Andrej; Pullman, John; Thompson, George R; Powderly, William G; Tobin, Ellis H; Vazquez, Jose; Wring, Stephen A; Angulo, David; Helou, Silvia; Pappas, Peter G; Mycoses Study Group; Vasquez, Jose; et al. (Journal of Antimicrobial Chemotherapy, 2019)
Objectives: To evaluate the safety and efﬁcacy of two dosing regimens of oral ibrexafungerp (formerly SCY078), a novel orally bioavailable b-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 lMÁh) in .80% of the intended population. Methods: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. Results: Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in $85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or ﬂuconazole. Similar favourable response rates were reported among all groups: 86% (n"6) in the ibrexafungerp 750 mg versus 71% (n"5) in both the ﬂuconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. Conclusions: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.

Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation - Boonyaratanakornkit, Jim; Vivek, Meghana; Xie, Hu; Pergam, Steven A; Cheng, Guang-Shing; Mielcarek, Marco; Hill, Joshua A; Jerome, Keith R; Limaye, Ajit P; Leisenring, Wendy; Boeckh, Michael J; Waghmare, Alpana (The Journal of Infectious Diseases, 2019)
Background.  Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. Methods.  Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. Results.  Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0). Conclusions.  High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.

Potential Fifth Clade of Candida auris, Iran, 2018 - Chow, Nancy A.; de Groot, Theun; Badali, Hamid; Abastabar, Mahdi; Chiller, Tom M.; Meis, Jacques F. (Emerging Infectious Diseases, 2019)
Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.

RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Manuel, Oriol; Estabrook, Michele (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of RNA respiratory viral infections in the pre‐ and post‐transplant period. Viruses reviewed include influenza, respiratory syncytial virus (RSV), parainfluenza, rhinovirus, human metapneumovirus (hMPV), and coronavirus. Diagnosis is by nucleic acid testing due to improved sensitivity, specificity, broad range of detection of viral pathogens, automatization, and turnaround time. Respiratory viral infections may be associated with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. The cornerstone of influenza prevention is annual vaccination and in some cases antiviral prophylaxis. Treatment with neuraminidase inhibitors and other antivirals is reviewed. Prevention of RSV is limited to prophylaxis with palivizumab in select children. Therapy of RSV upper or lower tract disease is controversial but may include oral or aerosolized ribavirin in some populations. There are no approved vaccines or licensed antivirals for parainfluenza, rhinovirus, hMPV, and coronavirus. Potential management strategies for these viruses are given. Future studies should include prospective trials using contemporary molecular diagnostics to understand the true epidemiology, clinical spectrum, and long‐term consequences of respiratory viruses as well as to define preventative and therapeutic measures.

Inflammatory and Infectious Syndromes Associated With Cancer Immunotherapies - Fishman, Jay A.; Hogan, John I.; Maus, Marcela V. (Clinical Infectious Diseases, 2019)
Abstract. Immunotherapy using antibodies to immune checkpoint molecules or targeted chimeric antigen receptor-modified T cells (CAR-T cells) represent dramatic

On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds - Casadevall, Arturo; Kontoyiannis, Dimitrios P.; Robert, Vincent (mBio, 2019)

Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7) - Ljungman, Per; Camara, Rafael de la; Robin, Christine; Crocchiolo, Roberto; Einsele, Hermann; Hill, Joshua A.; Hubacek, Petr; Navarro, David; Cordonnier, Catherine; Ward, Katherine N. (The Lancet Infectious Diseases, 2019)
Summary Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease. Antiviral drugs including maribavir and letermovir are in development and prospective clinical trials have recently been completed. However, management of patients with resistant or refractory cytomegalovirus infection or cytomegalovirus disease is a challenge. In this Review we summarise the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies.

Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens - Friedman, Daniel Z.P.; Schwartz, Ilan S. (Journal of Fungi, 2019)
The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation - Silva, Jose Tiago; San-Juan, Rafael; Fernández-Ruiz, Mario; Aguado, José María (World Journal of Gastroenterology, 2019)
Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.

Food Safety Tips for Transplant Recipients - Power2Save (American Society of Transplantation, 2019)
Make a difference in the field of transplantation by donating to support our cause.

Top Questions in the Diagnosis and Treatment of Pulmonary M. abscessus Disease - Nathavitharana, Ruvandhi R.; Strnad, Luke; Lederer, Philip A.; Shah, Maunank; Hurtado, Rocio M. (Open Forum Infectious Diseases, 2019)
Mycobacterium abscessus pulmonary disease is particularly challenging to treat, given its intrinsic drug resistance and limited data to guide management. In thi

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis - Wilson, Michael R.; Sample, Hannah A.; Zorn, Kelsey C.; Arevalo, Shaun; Yu, Guixia; Neuhaus, John; Federman, Scot; Stryke, Doug; Briggs, Benjamin; Langelier, Charles; Berger, Amy; Douglas, Vanja; et al. (New England Journal of Medicine, 2019)

Antibiotic Treatment Versus No Treatment for Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Multicenter Randomized Trial - Sabé, Núria; Oriol, Isabel; Melilli, Edoardo; Manonelles, Anna; Bestard, Oriol; Polo, Carolina; Los Arcos, Ibai; Perelló, Manel; Garcia, Dolors; Riera, Lluís; Tebé, Cristian; Len, Òscar; et al. (Open Forum Infectious Diseases, 2019)
Background.  Whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. Methods.  In this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. Results.  We enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40–4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50–8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P = .030), amoxicillin-clavulanic (P < .001) resistance, and extended-spectrum β-lactamase production (P = .044) were more common in KT recipients receiving antibiotic treatment for AB. Conclusions.  Antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed.

Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort - Van de Wyngaert, Zoé; Berthon, Céline; Debarri, Houria; Bories, Claire; Bonnet, Sarah; Nudel, Morgane; Carpentier, Benjamin; Legrand, Charline; Barbieux, Sarah; Chauvet, Paul; Simonnet, Arthur; Willaume, Alexandre; et al. (International Journal of Antimicrobial Agents, 2019)
Objectives Antibiotics for febrile neutropenia (FN) in acute myeloid leukaemia (AML) patients undergoing intensive chemotherapy are usually maintained until neutropenia resolution, because of the risk of uncontrolled sepsis in this vulnerable population. This leads to unnecessarily prolonged antimicrobial therapy. Methods Based on ECIL-4 recommendations, we modified our management strategy and discontinued antibiotics after a pre-established duration in patients treated for a first episode of FN between August 2014 and October 2017. Results Antibiotics were stopped during 62 FN episodes, and maintained in the control group (n = 13). Median age of patients was 54 years. A total of 39 (63%) patients received induction and 23 (37%) consolidation chemotherapy; 36 (58%) patients had fever of unknown origin. Median neutropenia length was 26 days (IQR 24–30). Antibiotics were started at day 9 (IQR 5–13). Most patients received piperacillin-tazobactam (56%) or cefepime (32%). Antimicrobial therapy was longer in the control group than in the policy compliant group, 10 (IQR 7–16) vs. 19 days (IQR 15–23), P = 0.0001. After antibiotics discontinuation, 20% patients experienced fever recurrence, within 5.5 days (IQR 3–7.5). None of these febrile episodes were severe and 80% patients remained afebrile, with neutrophil recovery occurring within 5 days (IQR 2–8.5). Overall, 287 antibiotics days were spared; this represents 49% of all days with antibiotics. No patient had died at day 30 from intervention; six died during late follow-up, two from graft-versus-host disease and four from relapsed or refractory leukaemia. Conclusions Discontinuing antibiotics in neutropenic AML patients treated for a first episode of FN is safe, and results in significant antibiotic sparing.
Keywords: Acute myeloid leukaemia; ECIL-4; antibiotics discontinuation; febrile neutropenia

Fluoroquinolone Prophylaxis Selects for Meropenem-nonsusceptible Pseudomonas aeruginosa in Patients With Hematologic Malignancies and Hematopoietic Cell Transplant Recipients - Hakki, Morgan; Humphries, Romney M.; Hemarajata, Peera; Tallman, Gregory B.; Shields, Ryan K.; Mettus, Roberta T.; Doi, Yohei; Lewis, James S. (Clinical Infectious Diseases, 2019)
Fluoroquinolone prophylaxis in neutropenic, hematologic malignancy patients and hematopoietic-transplant recipients is associated with breakthrough bacteremia w

Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial - Kullberg, Bart Jan; Viscoli, Claudio; Pappas, Peter G.; Vazquez, Jose; Ostrosky-Zeichner, Luis; Rotstein, Coleman; Sobel, Jack D.; Herbrecht, Raoul; Rahav, Galia; Jaruratanasirikul, Sutep; Chetchotisakd, Ploenchan; Van Wijngaerden, Eric; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2019)
BACKGROUND: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. METHODS: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. RESULTS: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9--1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. CONCLUSIONS: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. CLINICAL TRIALS REGISTRATION: NCT00413218.
Keywords: Adult; Aged; Candida; Candidemia; Candidiasis, Invasive; Caspofungin; Female; Humans; Male; Middle Aged; Nitriles; Pyridines; Treatment Outcome; Triazoles; caspofungin; isavuconazole; voriconazole

A Randomized Study of Quantiferon CMV-directed Versus Fixed-duration Valganciclovir Prophylaxis to Reduce Late CMV After Lung Transplantation - Westall, Glen P.; Cristiano, Yvonne; Levvey, Bronwyn J.; Whitford, Helen; Paraskeva, Miranda A.; Paul, Eldho; Peleg, Anton Y.; Snell, Gregory I. (Transplantation, 2019)
Background. We provide the results of the first interventional study of cytomegalovirus (CMV)-specific immune monitoring to direct the length of antiviral prophylaxis in lung transplantation (LTx). Methods. Patients (n = 118) at risk of CMV infection were randomized 1:2 to either 5 months or variable length valganciclovir prophylaxis (5–11 mo post-LTx), as determined by the QuantiFERON (QFN)-CMV assay. Patients with a negative QFN-CMV assay (< 0.2 IU/mL) received prolonged valganciclovir prophylaxis. Results. The primary endpoint that was the incidence of CMV infection in the lung allograft within 18 months of LTx was significantly reduced in the QFN-CMV directed arm (37% versus 58%, P = 0.03). Secondary endpoints that included blood viremia, acute rejection, and chronic lung allograft dysfunction did not differ between the 2 arms. Of the 80/118 patients who ceased antiviral prophylaxis at 5 months, the incidence of viremia (> 600 copies/mL) within the blood was significantly reduced in patients with a positive QFN-CMV assay compared with those without protective immunity (13% versus 67%, P = 0.0003), as was the incidence of severe viremia (> 10 000 copies/mL) (3% versus 50%, P < 0.001). Ceasing antiviral prophylaxis at 11 months in patients with a negative assay was associated with a 25% incidence of late CMV viremia. Conclusions. Cytomegalovirus immune monitoring allows an individualized approach to CMV prophylaxis and reduces late CMV infection within the lung allograft.

People at Risk: Those with Weakened Immune Systems - Affairs (ASPA), Assistant Secretary for Public (2019)
Find out why people with health problems or who take medicines that weaken the body’s ability to fight germs and sickness are more likely to get a foodborne illness.

Personas en riesgo: personas con sistemas inmunitarios debilitados - Affairs (ASPA), Assistant Secretary for Public (2019)
Find out why people with health problems or who take medicines that weaken the body’s ability to fight germs and sickness are more likely to get a foodborne illness.

Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy - Cortese, Irene; Muranski, Pawel; Enose-Akahata, Yoshimi; Ha, Seung-Kwon; Smith, Bryan; Monaco, MariaChiara; Ryschkewitsch, Caroline; Major, Eugene O.; Ohayon, Joan; Schindler, Matthew K.; Beck, Erin; Reoma, Lauren B.; et al. (The New England Journal of Medicine, 2019)
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. Programmed cell death protein 1 (PD-1) is a negative regulator of the immune response that may contribute to impaired viral clearance. Whether PD-1 blockade with pembrolizumab could reinvigorate anti-JC virus immune activity in patients with PML was unknown. METHODS: We administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condition. Each patient received at least one dose but no more than three doses. RESULTS: Pembrolizumab induced down-regulation of PD-1 expression on lymphocytes in peripheral blood and in cerebrospinal fluid (CSF) in all eight patients. Five patients had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in the CSF and an increase in in vitro CD4+ and CD8+ anti-JC virus activity. In the other three patients, no meaningful change was observed in the viral load or in the magnitude of antiviral cellular immune response, and there was no clinical improvement. CONCLUSIONS: Our findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus; clinical improvement or stabilization occurred in five of the eight patients who received pembrolizumab. Further study of immune checkpoint inhibitors in the treatment of PML is warranted. (Funded by the National Institutes of Health.).
Keywords: Adult; Aged; Antibodies, Monoclonal, Humanized; Brain; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cerebrospinal Fluid; Down-Regulation; Female; Humans; Immune Reconstitution Inflammatory Syndrome; Immunologic Factors; JC Virus; Leukoencephalopathy, Progressive Multifocal; Lymphocyte Count; Magnetic Resonance Imaging; Male; Middle Aged; Programmed Cell Death 1 Receptor; Viral Load; White Matter

Treatment of Progressive Multifocal Leukoencephalopathy with Pembrolizumab - Rauer, Sebastian; Marks, Reinhard; Urbach, Horst; Warnatz, Klaus; Nath, Avindra; Holland, Steve; Weiller, Cornelius; Grimbacher, Bodo (The New England Journal of Medicine, 2019)
Keywords: Antibodies, Monoclonal, Humanized; Brain; CD8-Positive T-Lymphocytes; Cerebrospinal Fluid; Humans; Immunologic Factors; JC Virus; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Programmed Cell Death 1 Receptor; Viral Load; White Matter

Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients - Woolley, Ann E.; Singh, Steve K.; Goldberg, Hilary J.; Mallidi, Hari R.; Givertz, Michael M.; Mehra, Mandeep R.; Coppolino, Antonio; Kusztos, Amanda E.; Johnson, Megan E.; Chen, Kaiwen; Haddad, Esther A.; Fanikos, John; et al. (New England Journal of Medicine, 2019)
HCV-Positive Organ Donors In patients without hepatitis C virus infection who received a heart or lung from HCV-infected donors, 4 weeks of antiviral treatment initiated after surgery rendered all 35 recipients who had completed 6 months of follow-up free of HCV infection despite early signs of infection in 96% of the recipients within hours after surgery.

Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials - Chemaly, Roy F.; Chou, Sunwen; Einsele, Hermann; Griffiths, Paul; Avery, Robin; Razonable, Raymund R.; Mullane, Kathleen M.; Kotton, Camille; Lundgren, Jens; Komatsu, Takashi E.; Lischka, Peter; Josephson, Filip; et al. (Clinical Infectious Diseases, 2019)
Standardized consensus definitions for resistant and refractory cytomegalovirus (CMV) infections and diseases in transplant recipients were developed by the CMV

Incidence Rates and Risk Factors of Clostridioides difficile Infection in Solid Organ and Hematopoietic Stem Cell Transplant Recipients - Ilett, Emma E.; Helleberg, Marie; Reekie, Joanne; Murray, Daniel D.; Wulff, Signe M.; Khurana, Mark P.; Mocroft, Amanda; Daugaard, Gedske; Perch, Michael; Rasmussen, Allan; Sørensen, Søren S.; Gustafsson, Finn; et al. (Open Forum Infectious Diseases, 2019)
AbstractBackground. Transplant recipients are an immunologically vulnerable patient group and are at elevated risk of Clostridioides difficile infection (CDI)

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of Americaa - Nicolle, Lindsay E; Gupta, Kalpana; Bradley, Suzanne F; Colgan, Richard; DeMuri, Gregory P; Drekonja, Dimitri; Eckert, Linda O; Geerlings, Suzanne E; Köves, Béla; Hooton, Thomas M; Juthani-Mehta, Manisha; Knight, Shandra L; et al. (Clinical Infectious Diseases, 2019)

Management of Patients With Fever and Neutropenia Through the Arc of Time: A Narrative Review - Pizzo, Philip A. (Annals of Internal Medicine, 2019)

Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016 - Pfaller, Michael A; Diekema, Daniel J; Turnidge, John D; Castanheira, Mariana; Jones, Ronald N (Open Forum Infectious Diseases, 2019)
Background.  The emergence of antifungal resistance threatens effective treatment of invasive fungal infection (IFI). Invasive candidiasis is the most common health care–associated IFI. We evaluated the activity of fluconazole (FLU) against 20 788 invasive isolates of Candida (37 species) collected from 135 medical centers in 39 countries (1997–2016). The activity of anidulafungin, caspofungin, and micafungin (MCF) was evaluated against 15 308 isolates worldwide (2006–2016). Methods.  Species identification was accomplished using phenotypic (1997–2001), genotypic, and proteomic methods (2006–2016). All isolates were tested using reference methods and clinical breakpoints published in the Clinical and Laboratory Standards Institute documents. Results.  A decrease in the isolation of Candida albicans and an increase in the isolation of Candida glabrata and Candida parapsilosis were observed over time. Candida glabrata was the most common non–C. albicans species detected in all geographic regions except for Latin America, where C. parapsilosis and Candida tropicalis were more common. Six Candida auris isolates were detected: 1 each in 2009, 2013, 2014, and 2015 and 2 in 2016; all were from nosocomial bloodstream infections and were FLU-resistant (R). The highest rates of FLU-R isolates were seen in C. glabrata from North America (NA; 10.6%) and in C. tropicalis from the AsiaPacific region (9.2%). A steady increase in isolation of C. glabrata and resistance to FLU was detected over 20 years in the United States. Echinocandin-R (EC-R) ranged from 3.5% for C. glabrata to 0.1% for C. albicans and C. parapsilosis. Resistance to MCF was highest among C. glabrata (2.8%) and C. tropicalis (1.3%) from NA. Mutations on FKS hot spot (HS) regions were detected among 70 EC-R isolates (51/70 were C. glabrata). Most isolates harboring FKS HS mutations were resistant to 2 or more ECs. Conclusions.  EC-R and FLU-R remain uncommon among contemporary Candida isolates; however, a slow and steady emergence of resistance to both antifungal classes was observed in C. glabrata and C. tropicalis isolates.

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza - Uyeki, Timothy M.; Bernstein, Henry H.; Bradley, John S.; Englund, Janet A.; File, Thomas M.; Fry, Alicia M.; Gravenstein, Stefan; Hayden, Frederick G.; Harper, Scott A.; Hirshon, Jon Mark; Ison, Michael G.; Johnston, B. Lynn; et al. (Clinical Infectious Diseases, 2019)
Abstract. These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to t

Effect of Neutropenic Diet on Infection Rates in Cancer Patients With Neutropenia: A Meta-analysis of Randomized Controlled Trials - Ball, Somedeb; Brown, Timothy J.; Das, Avash; Khera, Rohan; Khanna, Sahil; Gupta, Arjun (American Journal of Clinical Oncology, 2019)
Introduction: Neutropenic diets are commonly prescribed to cancer patients with neutropenia with the intention of reducing rates of infection. These diets are restrictive and are associated with lower patient satisfaction and possibly malnutrition. Further, it is unclear if these restrictive diets are effective in reducing infection. We performed a meta-analysis on the rates of infection reported in trials comparing the neutropenic diet to unrestricted diets in cancer patients with neutropenia. Methods and Materials: A comprehensive database search for all published randomized controlled trials comparing infection rates in cancer patients receiving a neutropenic diet versus an unrestricted diet was performed for all publications in English language from database’s inception until September 12, 2017. The search strategy, study selection, and subsequent analysis adhered to PRISMA guidelines. Random effects modeling was used to obtain pooled relative risks. The primary outcome measure was the rate of infection. Results: Five randomized controlled trials with a total of 388 patients were included in the final analysis. Patients mostly had acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or sarcoma. Infection was noted in 53.7% patients in the neutropenic diet group, as compared with 50% in the unrestricted diet group. No significant difference in infection rate was observed between the neutropenic diet versus unrestricted diet groups, pooled risk ratio (RR) 1.13 (95% CI, 0.98-1.30; P=0.10). Conclusions: This meta-analysis of randomized controlled trials suggests that the use of neutropenic diet was not associated with decreased risk of infection in neutropenic cancer patients. The continued use of neutropenic diets should be questioned.

For Patients | MRSA | CDC (2019)
General information about MRSA—the risks and treatments.

Infections in patients using ventricular-assist devices: Comparison of the diagnostic performance of 18F-FDG PET/CT scan and leucocyte-labeled scintigraphy - de Vaugelade, Carole; Mesguich, Charles; Nubret, Karine; Camou, Fabrice; Greib, Carine; Dournes, Gael; Debordeaux, Frédéric; Hindie, Elif; Barandon, Laurent; Tlili, Ghoufrane (Journal of Nuclear Cardiology, 2019)
The usage of left-ventricular-assist device (LVAD) is increasing in patients presenting with advanced heart failure. However, device-related infections are a challenge to recognize and to treat, with an important morbidity and mortality rate. The role of nuclear medicine imaging remains not well established for LVAD infections. The present study compared the accuracy of positron emission tomography/computed tomography with 18F-fludeoxyglucose (18F-FDG PET/CT) and radiolabeled leucocyte scintigraphy for the diagnosis of infections in patients supported with a continuous-flow LVAD.

Brucellosis After Cardiac Transplantation - Nair, Vinitha V.; Appukuttan, Murali; Narayan, Kiran Vishnu; Nair, Jayakumar Thanathu Krishnan (The Annals of Thoracic Surgery, 2019)

Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Abbo, Lilian M.; Grossi, Paolo Antonio; the AST ID Community of Practice (Clinical Transplantation, 2019)
These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post‐operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%‐53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end‐stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug‐resistant organisms.

Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Allen, Upton D.; Preiksaitis, Jutta K.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, management, and prevention of post-transplant lymphoproliferative disorders (PTLD) and other Epstein-Barr virus (EBV) syndromes after solid organ transplantation. PTLD are a heterogeneous spectrum of predominantly B-cell disorders, often extra-nodal, with complex distinct pathogeneses and variable clinical presentations determined by pathologic subtype. Recent epidemiologic studies report a decrease in early EBV-positive (+) PTLD and an increase in late EBV-negative (−) PTLD. Pre-transplant EBV-seronegativity and primary EBV infection, often from donor-transmitted infection, are an important risk factors for EBV syndromes and early EBV + PTLD. Low-quality evidence supports preemptive prevention strategies for early EBV + PTLD in EBV-seronegative recipients that involve EBV DNA measurement in peripheral blood using assays requiring further result harmonization, combined with interventions to lower viral load. Reduction in immunosuppression (RIS) is the best validated intervention. WHO pathology classification of a tissue biopsy remains the gold standard for PTLD diagnosis; optimal staging procedures are uncertain. Treatment of CD20+ PTLD with the response-dependent sequential use of RIS, rituximab, and cytotoxic chemotherapy is recommended. Evidence gaps requiring future research and alternate treatment strategies including immunotherapy are highlighted.
Keywords: Epstein-Barr virus; Epstein–Barr virus (EBV); PTLD; lymphoproliferation; post-transplant lymphoproliferative disorder; rituximab; viral infection

Antibiotic Consideration in Transplant Recipients - Altshuler, Jerry; Aitken, Samuel L.; Maslow, Melanie; Papadopoulos, John; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Transplant patients are uniquely predisposed to infections with multidrug-resistant organisms both in the early and late phases after transplantation. Similarly, recipients of stem cell or solid organ allograft show greater susceptibility for often difficult-to-treat infections acquired during the extensive healthcare environmental contact and multidrug-resistant bacteria in patients’ community. Infections are frequently encountered during pretransplant period due to the undergoing neoplastic processes or end-stage organ disease and rarely unwittingly transmitted via an infected donor graft. Major risk factors for infections following transplantation procedures include prolonged hospitalization, prior systemic antibiotic exposure, surgeries, need for critical care unit stay, mechanical ventilation, and presence of indwelling intravascular and other body cavity devices. Antibiotic regimens are often more complex and in a vast number of transplant patients given empirically or preemptively. Drug-drug interactions with immunosuppressive medications and serious, treatment-limiting adverse reactions further complicate management of these high-risk individuals. Use of prophylactic antibiotics also contributes to selection of antibiotic resistance organisms and rarely development of de novo drug-resistant pathogen. Multiple studies have documented increased morbidity and mortality in the transplant population, especially due to bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia, methicillin-resistant S. aureus, and vancomycin-resistant enterococci. This chapter will focus on the major classes of antibiotics including conventional drugs and new antimicrobials in development, mechanisms of resistance, and the indications for use in the transplant population.
Keywords: Aerosolized; Antibiotics; Area under the concentration curve (AUC); Bacterial infections; Bioavailability (F); Drug interaction; Drug toxicity; Immunomodulation; Investigational; Mechanism of action; Minimum inhibitory concentration (MIC); Therapeutic drug monitoring (TDM); Transplantation; Volume of distribution (Vd)

Arenaviruses and West Nile Virus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Anesi, Judith A.; Silveira, Fernanda P.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the epidemiology, diagnosis, prevention, and management of infection due to Arenaviruses and West Nile Virus (WNV) in the pre- and post-transplant period. Arenaviruses and WNV have been identified as causes of both donor-derived and post-transplant infection. Most data related to these infections have been published in case reports and case series. Transplant recipients may become infected with Arenaviruses if they, or their donors, are exposed to wild rodents or infected pet rodents. Lymphocytic choriomeningitis virus is the most commonly recognized Arenavirus among transplant recipients and should be considered when transplant recipients present with fever, hepatitis, meningitis/encephalitis, and/or multisystem organ failure. WNV is a mosquito-borne virus, and as such, its incidence varies yearly depending on environmental conditions. WNV in transplant recipients typically presents with fever, myalgias, and rash; approximately one in 40 develop neuroinvasive disease. Due to its morbidity, the Organ Procurement and Transplantation Network recently mandated that transplant centers screen living donors for WNV infection in endemic areas. Little is known about the optimal treatment of Arenaviruses or WNV; reduction in immunosuppression and supportive care are the mainstays of management at present.
Keywords: West Nile; donor-derived infections; donors and donation; infection and infectious agents; infectious; viral

Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Angarone, Michael; Snydman, David R.; Practice, the AST ID Community of (Clinical Transplantation, 2019)
These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of diarrhea in the pre- and post-transplant period. Diarrhea in an organ transplant recipient may result in significant morbidity including dehydration, increased toxicity of medications, and rejection. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common. Further, noninfectious causes including medication toxicity, inflammatory bowel disease, post-transplant lymphoproliferative disease, and malignancy can also result in diarrhea in the transplant population. Management of diarrhea in this population is directed at the cause of the diarrhea, instituting therapy where appropriate and maintaining proper hydration. Identification of the cause to the diarrhea needs to be timely and focused.
Keywords: Clostridium difficile; antibacterial; cytomegalovirus; diarrhea; infection and infectious agents; infectious; norovirus; solid Organ Transplant

Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Aslam, Saima; Rotstein, Coleman; Practice, the AST Infectious Disease Community of (Clinical Transplantation, 2019)
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice provide recommendations for the diagnosis and management of Candida infections in solid organ transplant recipients. Candida infections manifest primarily as candidemia and invasive candidiasis and cause considerable morbidity and mortality. Early diagnosis and initiation of treatment are necessary to reduce mortality. For both candidemia and invasive candidiasis, an echinocandin is recommended for initial therapy. However, early transition to oral therapy is encouraged when patients are stable and the organism is susceptible. Candida prophylaxis should be targeted for high-risk patients in liver, small bowel, and pancreas transplant recipients. Future research should address which patient groups may benefit most from preventative antifungal therapy strategies.
Keywords: antifungal; fungal; infection and infectious; infection and infectious agents

Strategies for safe living following solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Avery, Robin K.; Michaels, Marian G.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
The present AST-IDCOP guidelines update information on strategies for safe living after organ transplantation. While transplantation carries an increased risk for infection from the recipient's environment due to lifelong immunosuppression, the goal is for the recipient to be able to return to their home and live as normal a life as possible with a functioning graft. The current guideline provides updates to prior recommendations including additions on infections from water and food sources, exposures to animals, cannabis use as well as sexual exposures or those encountered with travel. Similar to the prior editions, many of the recommendations are based on good infection prevention standards, extrapolation from other immunocompromised hosts, and risks found from cases series in transplant patients. Enhanced education and attention to incorporating safe living strategies into daily life should help to accomplish successful transplant with recipients achieving a fulfilling life away from the hospital.
Keywords: complication; guidelines; infection and infectious agents; infection prevention; infectious

Viral Diagnostics - Avery, Robin K.; Yen-Lieberman, Belinda (Principles and Practice of Transplant Infectious Diseases, 2019)
This chapter discusses recent developments in diagnostics for cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), community respiratory viruses (CRVs), parvovirus, hepatitis viruses, HIV, and other viral agents of importance in solid organ and hematopoietic stem cell transplantation.
Keywords: BK virus; Community respiratory viruses; Cytomegalovirus; Epstein-Barr virus; Hepatitis viruses; Parvovirus; Transplant; Viral infections

The Use of Palliative Care in Organ Transplant Patients and End-of-Life Issues - Ayala, Jenny S.; Lowy, Joseph (Principles and Practice of Transplant Infectious Diseases, 2019)
Palliative care has been shown to improve quality of life and even prolong life in patients with certain types of malignancy and end-organ failure. Several studies have now demonstrated a beneficial impact of palliative care on the transplant patient. While hospice provides care for patients whose survival is expected to be less than 6 months, palliative care is the specialized care for the patient with serious illness and can be provided at any stage of the disease. All transplant candidates, by definition, qualify. Like transplant medicine, palliative care is also interdisciplinary. It is person/family centered and provides support along with aggressive symptom management. Patients are screened for pain and other physical symptoms as well as for psychosocial and spiritual distress. Palliative care also fosters communication between the patient/family and health-care providers. The patient’s values and principles are elicited so that concordant medical care is provided. Implementing palliative care, sometimes referred to as supportive care early in the disease trajectory has helped transition patients into hospice care once curative options have been exhausted. This chapter will elucidate why patients with organ failure who are candidates for transplantation or patients suffering from complications of transplantation are excellent candidates for palliative care and why a palliative care provider should be part of the transplant interdisciplinary team.
Keywords: Bone marrow transplantation; End-of-life care for transplant patients; End-stage heart failure; End-stage kidney failure; End-stage liver failure; End-stage lung failure; Importance of prognostication; Organ transplantation; Palliative Performance Scale; Prognosticating survival in non-cancer patients; Review of end-stage organ failure diseases and the role of palliative care; Role of palliative care; Symptom management in chronic illness and the role of palliative care; Understanding the difference between palliative and hospice care

Impacts and Challenges of Advanced Diagnostic Assays for Transplant Infectious Diseases - Babady, N. Esther; Lee, Yeon Joo; Papanicolaou, Genovefa; Tang, Yi-Wei (Principles and Practice of Transplant Infectious Diseases, 2019)
The advanced technologies described in this chapter should allow for full inventories to be made of bacterial genes, their time- and place-dependent expression, and the resulting proteins as well as their outcome metabolites. The evolution of these molecular technologies will continue, not only in the microbial pathogens but also in the context of host-pathogen interactions targeting human genomics and transcriptomics. Their performance characteristics and limitations must be clearly understood by both laboratory personnel and clinicians to ensure proper utilization and interpretation.
Keywords: Adenovirus; BD glucans; BK virus; Commutability; Culture; Cytomegalovirus; Galactomannan; Genomics; Human herpesvirus 6; Metabolomics; PCR; Polyomavirus; Proteomics; Standardization; Transcriptomics; Viral loads

Cryptococcosis in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Baddley, John W.; Forrest, Graeme N.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of cryptococcosis in the pre- and post-transplant period. The current update now includes a discussion of cryptococcosis, which is the third most common invasive fungal infection in SOT recipients. Infection often occurs a year after transplantation; however, early infections occur and donor-derived infections have been described within 3 months after transplant. There are two main species that cause infection, Cryptococcus neoformans and C gattii. Clinical onset may be insidious, but headaches, fevers, and mental status changes should warrant diagnostic testing. The lateral flow cryptococcal antigen assay is now the preferred test from serum and cerebrospinal fluid due to its rapidity, accuracy, and cost. A lumbar puncture with measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Lipid amphotericin B plus 5-flucytosine is used as initial treatment of meningitis, disseminated infection, and moderate-to-severe pulmonary infection, followed by fluconazole as consolidation therapy. Fluconazole is effective for mild-to-moderate pulmonary infection. Immunosuppression reduction as part of management may lead to immune reconstitution syndrome that may resemble active disease.
Keywords: antibiotic; antifungal; complication; fungal; infection and infectious agents; infectious

Cytopenias in Transplant Patients - Barry, Maura; Chandra, Sunandana; Hymes, Kenneth B. (Principles and Practice of Transplant Infectious Diseases, 2019)
Anemia, leukopenia, thrombocytopenia, as well as pancytopenias can be seen following solid organ transplant. Varying patterns of cytopenia can be seen based on the drugs used in the posttransplant period, infections encountered by the individual, as well as the individual’s immune response and bone marrow function. The chapter discusses the main causes of anemia, leukopenia/neutropenia, and thrombocytopenia. The differential diagnosis for anemia after solid organ transplant includes hemolysis, drug toxicities, iron deficiency, infection, posttransplant lymphoproliferative disorder, graft-vs.-host disease, and hemophagocytic syndrome. Etiologies for leukopenia and neutropenia include drug toxicities and infection, and etiologies for thrombocytopenia include drug toxicities, infections, autoimmune events such as immune thrombocytopenic purpura, and underlying causes such as persistent portal hypertension and splenomegaly.
Keywords: Anemia; Cytopenia; Leukopenia; Neutropenia; Pancytopenia; Thrombocytopenia

Isolation of antibiotic-resistant gram-negative organisms from donor respiratory culture does not impact non-lung solid organ recipient management - Benamu, Esther; Pereira, Marcus R.; Taimur, Sarah; Jacobs, Samantha E.; Friedman, Amy L.; Jenkins, Stephen G.; Herold, Betsy C.; Pellett Madan, Rebecca (Clinical Transplantation, 2019)
Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) gram-negative bacteria may be transmitted from organ donors to solid organ transplant recipients and are associated with poor outcomes post-transplant. Methods We reported the prevalence of MDR/XDR gram-negative respiratory colonization among 702 deceased organ donors in the New York City area from 2011 to 2014 and performed chart reviews for a subset of recipients to determine whether donor respiratory culture results were predictive of subsequent recipient infection or used to guide post-transplant antimicrobial therapy. Results Fifty donors (7% of the cohort) had MDR or XDR gram-negative bacteria isolated from endotracheal aspirate or bronchoalveolar lavage culture. Organs from these 50 donors were transplanted into 120 recipients; chart review was performed for 89 of these recipients (38 kidney, 32 liver, 11 heart, 6 kidney/pancreas, 1 liver/kidney, 1 lung). None of the 89 recipients of organs from donors with MDR/XDR gram-negative respiratory colonization were reported to have a donor-derived infection post-transplant, and chart review for the 88 non-lung recipients indicated that peri-transplant antibiotics were not adjusted specifically for donor respiratory culture results. Conclusion These results suggest that donor respiratory culture results are not predictive of post-transplant infection in non-lung recipients and are unlikely to impact post-transplant management.
Keywords: antibiotic prophylaxis; antimicrobial resistance; donor-derived infections

Parasitic Infections in Transplant Recipients: Toxoplasmosis, Strongyloidiasis, and Other Parasites - Blackburn, Brian G.; Montoya, José G. (Principles and Practice of Transplant Infectious Diseases, 2019)
Toxoplasma gondii and Strongyloides stercoralis are important parasitic infections in transplant recipients. These helminths can lead to severe and often life-threatening disease in immunocompromised patients. Toxoplasma gondii can cause an undifferentiated febrile syndrome, encephalitis, pneumonitis, myocarditis, hepatitis, and retinochoroiditis, whereas S. stercoralis infestation, can lead to the hyperinfection syndrome, which carries a high mortality rate. Effective therapies are available for both, but high case-fatality rates result if these syndromes go unrecognized and are not treated promptly. Preventative measures for infected (and often asymptomatic) transplant recipients/candidates are highly effective in preventing overt disease for both parasites, including prophylactic anti-Toxoplasma therapy or ivermectin treatment for patients with occult strongyloidiasis in properly selected patients. Identifying transplant patients at risk for these syndromes is therefore critical, so that these measures can be instituted before life-threatening disease develops. Other important parasitic infections in transplant recipients include Trypanosoma cruzi (the agent of Chagas disease), visceral leishmaniasis, and the free-living amoebae Acanthamoeba and Balamuthia.
Keywords: Acanthamoeba; Balamuthia; Chagas disease; Organ transplantation; Stem cell transplantation; Strongyloides stercoralis; Toxoplasma gondii; Trypanosoma cruzi; Visceral leishmaniasis

Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Blumberg, Emily A.; Rogers, Christin C.; Practice, the American Society of Transplantation Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the management of transplantation in HIV-infected individuals. Transplantation has become the standard of care for patients with HIV and end-stage kidney or liver disease. Although less data exist for thoracic organ and pancreas transplantation, it is likely that transplantation is also safe and effective for these recipients as well. Despite what is typically a transient decline in CD4+ T lymphocytes, HIV remains well controlled and infection risks are similar to those of HIV-uninfected transplant recipients. The availability of effective directly active antivirals for the treatment of Hepatitis C is likely to improve outcomes in HIV and HCV co-infected individuals, a population previously noted to have decreased survival. Drug interactions remain an important consideration, and integrase inhibitor-based regimens are preferred due to the absence of interactions with calcineurin and mTOR inhibitors. Additionally, despite the use of more potent immunosuppression, rejection rates exceed those found in HIV-uninfected recipients. Ongoing research evaluating HIV-positive organ donors may provide support for utilizing these donors for HIV-positive patients in need of transplantation.
Keywords: acquired immunodeficiency syndrome; human immunodeficiency virus

Infections in Limbs, Integuments, and Face Transplantation - Broyles, Justin M.; Gordon, Chad R. (Principles and Practice of Transplant Infectious Diseases, 2019)
Both facial and upper extremity composite tissue allotransplants consist of heterogeneous tissues including skin, muscle, bone, fat, nerves, and lymph nodes. These tissues are extremely antigenic and necessitate an immunosuppressive regimen similar to that of solid organ transplants. Thus, the patient with a face or limb transplant has many of the same infection risks in individuals following kidney transplantation such as nosocomial and opportunistic bacterial, viral, fungal, and protozoan infections. However, due to the exposed anatomy, possibility for mucosal exposure, and differing donor microflora, recipients of face or limb transplant are also susceptible to invasive diseases due to several different types of microbes. Here we present a comprehensive review of infections frequently encountered in patients undergoing solid organ transplantation with special attention to the brief experience in the prophylaxis and treatment of infection following composite tissue allotransplantation.
Keywords: CTA; Composite tissue allotransplantation; Face transplant; Hand transplant; Limb transplant

Travel medicine, transplant tourism, and the solid organ transplant recipient—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Buchan, C. Arianne; Kotton, Camille Nelson; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review recommendations for prevention and management of travel-related infection in solid organ transplant (SOT) recipients as well as risks associated with transplant tourism. Counseling regarding travel post-transplant should be included during the pre-transplant evaluation, and all SOT recipients should be seen by a travel medicine specialist prior to traveling to destinations with higher rates of infection. Patients should be advised on vaccine-preventable illnesses as well as any need for prophylaxis (ie, malaria) based on their individual travel itineraries. Information with regards to specific recommendations for vaccines and prophylactic medications, along with drug-drug interactions, is summarized. Counseling should be provided for modifiable risks and exposures (ie, food and water safety, and insect bite prevention) as well as non-infectious travel topics. These guidelines also briefly address risks associated with transplant tourism and specific infections to consider if patients seek care for transplants done in foreign countries.
Keywords: Vaccinations; solid organ transplant; travel medicine; vaccinations; vaccines

Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience - Cheng, Yao-Wen; Phelps, Emmalee; Ganapini, Vincent; Khan, Noor; Ouyang, Fangqian; Xu, Huiping; Khanna, Sahil; Tariq, Raseen; Friedman‐Moraco, Rachel J.; Woodworth, Michael H.; Dhere, Tanvi; Kraft, Colleen S.; et al. (American Journal of Transplantation, 2019)
Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.
Keywords: clinical research/practice; complication: infectious; immunosuppression/immune modulation; infection and infectious agents - bacterial: Clostridium difficile; infectious disease; intestinal disease: infectious; organ transplantation in general; patient safety

Human papillomavirus infection in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Chin-Hong, Peter V.; Reid, Gail E.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These guidelines from the American Society of Transplantation Infectious Diseases Community of Practice update the epidemiology and management of human papillomavirus (HPV) infections in organ transplant recipients. HPV is one of the most common sexually transmitted infections and is associated with cancers of the anogenital region. Increasing evidence suggests an association with head and neck cancers as well. Solid organ transplant recipients have a higher risk of HPV infection than the general population. Infection manifests as premalignant lesions, warts, or cancer of the cervix, penis, vulva, scrotum, and anal canal. Most are asymptomatic initially, so diagnosis can be difficult without screening. A vaccine is available though not effective in preventing all cancer-causing strains. Organ transplant recipients should be screened for HPV-associated cancers and appropriate therapy initiated in a timely manner. Further studies are warranted to delineate the most effective screening methods and therapeutic modalities, including whether changes in immunosuppression are effective in attenuating disease.
Keywords: Immunocompromised host; anal cancer; anal intraepithelial neoplasia; cervical cancer; cervical intraepithelial neoplasia; human papillomavirus; immunocompromised host; papillomaviridae; transplantation; vaccination

Antiviral Consideration for Transplantation Including Drug Resistance - Chou, Sunwen; Lurain, Nell S. (Principles and Practice of Transplant Infectious Diseases, 2019)
Antiviral therapy is required in the transplant setting for viral infections that arise from preexisting latent or persistent infection in the recipient and/or donor as well as from nosocomial or community sources. A preventive or prophylactic antiviral approach where feasible is preferable to the treatment of symptomatic viral disease. Acute infections need prompt diagnosis and antiviral treatment for the best outcome. Selection of antiviral therapy involves multiple considerations including potential benefit, toxicity, logistical complexity, and the possibility of drug resistance. This chapter reviews antiviral drug therapy for the most common viruses affecting transplant recipients: herpesviruses including herpes simplex virus, varicella-zoster virus, and cytomegalovirus, influenza, respiratory syncytial virus (RSV), and hepatitis viruses B and C. The mechanism of action, major pharmacologic features, therapeutic uses related to transplant recipients, and genetic pathways of antiviral drug resistance are described for the FDA-approved drugs and some experimental compounds in late stage clinical trial.
Keywords: Acyclovir; Adefovir; Amenamevir; Antiviral agents; Antiviral drug resistance; Brincidofovir; Brivudine; Cidofovir; Daclatasvir; Dasabuvir; Elbasvir; Entecavir; Famciclovir; Foscarnet; Ganciclovir; Glecaprevir; Grazoprevir; Lamivudine; Ledipasvir; Letermovir; Maribavir; Ombitasvir; Oseltamivir; Paritaprevir; Penciclovir; Peramivir; Pibrentasvir; Pritelivir; Ribavirin; Sofosbuvir; Tenofovir; Valacyclovir; Valganciclovir; Velpatasvir; Voxilaprevir; Zanamivir

Antifungal Stewardship: A Practical Guide to Implementation - Chun, Chinkah; Small, Ronald H.; Nagel, Jerod; Dodds Ashley, Elizabeth S (Joint Comission Resources, 2019)

Cutaneous Lesions that Mimic Infection in Transplant Patients - Ciurea, Ana; Hymes, Sharon (Principles and Practice of Transplant Infectious Diseases, 2019)
Dermatologists are often called upon to evaluate skin lesions in organ transplant patients, especially when an infectious etiology is suspected. This section will review some of the non-infectious skin eruptions that mimic cutaneous infections. This chapter is intended to help the clinician generate a differential diagnosis when evaluating cutaneous lesions in organ transplant patients. Using the morphology of the primary lesion as a starting point, we then list the non-infectious diagnosis that could be considered and the infectious process it mimics.
Keywords: Diagnostic clues; Immunosuppression; Mimic infection; Organ transplantation; Skin disorders

Listeriosis - Clauss, Heather E.; Lorber, Bennett (Principles and Practice of Transplant Infectious Diseases, 2019)
Listeria monocytogenes, a small gram-positive bacterium, is a foodborne pathogen that can cause life-threatening bacteremia and central nervous system infections. Persons at risk for listeriosis are primarily those with impairments in cell-medicated immune function, including recipients of solid organ and bone marrow transplantation. Although infection with this microorganism is uncommon, it carries a high mortality. CNS infection may have a subacute course and may involve the brain parenchyma as well as the meninges. Diagnosis usually requires isolation of the bacterium from normally sterile body fluids.
Keywords: CNS infection; Immunosuppression; Listeria; Listeriosis; Transplant

Nocardiosis and Actinomycosis - Clauss, Heather E.; Lorber, Bennett (Principles and Practice of Transplant Infectious Diseases, 2019)
Nocardia species are strictly aerobic, gram-positive, branching, filamentous rods which are beaded appearing and stained variably with the modified acid-fast Kinyoun stain. They can fragment into pleomorphic, rod-shaped, or coccoid pieces. Nocardia are sometimes difficult to recognize and identify in the laboratory, leading to delays in clinical diagnosis. Their relatively slow growth can result in the cultures being discarded before the colonies can be seen. Nocardia are found most often in the environment in soil, water, and vegetation. More than half of the time, these organisms are opportunistic pathogens, causing disease in both solid organ and stem cell transplantations. Less recognized as opportunistic pathogens are Actinomyces species, gram-positive, anaerobic bacilli which are not acid-fast. These organisms are morphologically similar to Nocardia species and can be confused on Gram staining. Nocardia and Actinomycetes cause distinct syndromes which will be reviewed here.
Keywords: Actinomycosis; Brain abscess; Nocardiosis; Organ transplantation; Pneumonia

Infection Control Strategies in Transplant Populations - Cutro, S.; Phillips, M.; Horowitz, H. W. (Principles and Practice of Transplant Infectious Diseases, 2019)
Infection control and prevention strategies are of great importance to the healthcare system as a whole, but are even more critical in the immunocompromised host. While transplant recipients present unique challenges to clinicians and infection control practitioners alike, standard approaches to infection control are still of foremost importance in this population. The type of transplantation, degree of immune suppression, and duration of time following transplantation help determine the risk of developing infections with various pathogens, and this chapter will address potentially preventable infections as a function of time after transplantation.
Keywords: Infection control and prevention; Opportunistic infections

Vaccination in Organ Transplant Patients - Danziger-Isakov, Lara; Kotton, Camille Nelson (Principles and Practice of Transplant Infectious Diseases, 2019)
Vaccines are an essential component of protection against infection after solid organ transplantation for both children and adults. Unfortunately, many transplant recipients are undervaccinated. In general, vaccination before transplantation results in better immunologic response, and the period before transplant is a special opportunity to provide protection for this vulnerable population. Live vaccines, such as MMR, varicella/zoster, nasal influenza, yellow fever, oral polio, and others are generally contraindicated after transplant. While the immunologic response induced by vaccination may be less robust in this population, due to exogenous immunosuppression, organ disease, and other comorbidities, this protection may be sufficient to protect or attenuate disease. Various individual vaccines are discussed in detail in this review.
Keywords: Immunity; Immunization; Prevention; Protection; Transplant; Vaccine

Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice - Danziger-Isakov, Lara; Kumar, Deepali; Practice, The AST ID Community of (Clinical Transplantation, 2019)
These updated guidelines of the AST IDCOP review vaccination of solid organ transplant candidates and recipients. General principles of vaccination as well as the use of specific vaccines in this population are discussed. Vaccination should be reviewed in the pre-transplant setting and appropriate vaccines updated. Both inactivated and live vaccines can be given pre-transplant. The timing of vaccination post-transplant should be taken into account. In the post-transplant setting, inactivated vaccines can be administered starting at 3 months post-transplant with the exception of influenza which can be given as early as one month. Inactivated vaccines can be safely administered post-transplant. There is accumulating data that live-attenuated vaccines can also be given to select post-transplant patients. Close contacts of transplant patients can receive most routine live vaccines. Specific vaccines including pneumococcal, influenza, hepatitis B, HPV, and meningococcal vaccines are discussed. Newer vaccines for seasonal influenza vaccine and herpes zoster are highlighted. Live-attenuated vaccines such as measles, mumps, rubella, and varicella are also discussed. Emerging data on live-attenuated vaccines post-transplant are highlighted.
Keywords: immunogenicity; infection and; infection and infectious agents; infectious agents; meningococcal; pneumococcal; vaccine; viral: hepatitis B; viral: herpes zoster/Varicella; viral: influenza; viral: papillomavirus

Immunotherapy for Invasive Mold Disease in Transplant Patients: Dendritic Cell Immunotherapy, Interferon Gamma, Recombinant Myeloid Growth Factors, and Healthy Donor Granulocyte Transfusions - Decker, William K.; Halpert, Matthew M.; Konduri, Vanaja; Liang, Dan; Hampton, Christopher N.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Over the last half-century, there has been a steady increase in opportunistic fungal infections due to the growth in population of patients with severe and mostly iatrogenically induced immune suppression. The explosive growth of this challenge in opportunistic fungal disease has been fueled in recent decades by advances in solid organ and hematopoietic stem cell transplantation. Furthermore, use of high-dose antineoplastic chemotherapy and biologic immunosuppressive regimens in oncology and clinical practice has further escalated the risk for opportunistic infections. Systemic antifungal therapies that work relatively well within the general population are far less efficacious in patients with severe immune dysregulation. This provides an important thrust and impetus for exploring novel antifungal immune modulation strategies. Here we outline a variety of potential novel adjunct treatment paradigms in the areas of whole cell, cytokine, and small-molecule therapies that may assist in amelioration of invasive fungal disease among patients in the setting of transplantation.
Keywords: Antifungals; Dendritic cell; Fungal infections; G-CSF; GM-CSF; Granulocyte transfusions; Interferon gamma; Mold

Antifungal Consideration for Transplant Recipients - Dubrovskaya, Yanina; Merl, Man Yee; Perlin, David S.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Invasive fungal infections (IFIs) continue to pose a serious challenge in patients undergoing transplantation. An essential need for treatment with immunosuppressive drugs necessary for sustenance of solid organ allograft; preparatory conditioning regimens use to facilitate hematopoietic stem cell engraftment; drugs given to mitigate hosts’ adaptive cellular immune response for prevention and treatment of graft-versus-host disease (GVHD), and visceral allgraft rejection promote the risk for opportunistic fungal disease. Despite the availability of new-generation diagostic assays, and availability of new antifungal drugs, IFIs continue to pose a serious challenge in the care for patients undergoing transplantation. For prevention and treatment of invasive fungal disease, systemic antifungal drugs are given episodically during the high-risk periods or for extended duration to maintain primary, or secondary suppression after successful resolution of an IFI episode. Selection of appropriate antifungal agent relies upon a number of factors that include patients' susceptibility for infection, spectrum of antimicrobial activity, drug toxicity profile, potential for drug-drug interaction, and clinical efficacy of various classes of antifungal compounds. In authors’ opinion, the role of antifungal drugs in eliciting and promoting drug resistance among clinically relevant fungi should also be an important part of the drug selection process. In this chapter, a review of antifungal drugs with a focus on drug resistance is provided.
Keywords: Amphotericin; Anidulafungin; Antifungal agents; Caspofungin; Fluconazole; Micafungin; Posaconazole; Resistance; Voriconazole

Diagnosis of Systemic Fungal Diseases - Dufresne, Simon Frédéric; Marr, Kieren A.; Shoham, Shmuel (Principles and Practice of Transplant Infectious Diseases, 2019)
Invasive fungal infections (IFI) are a major cause of morbidity and mortality in transplant recipients. The most common IFI are candidiasis, aspergillosis, pneumocystosis, cryptococcosis, mucormycosis, and endemic mycoses. Clinical presentations are generally non-specific, and fungal etiologies are often suspected when immunocompromised patients present with respiratory symptoms and/or undifferentiated fever that do not respond to empiric antibacterial therapy. Moreover, early treatment can be lifesaving. Consequently, diagnosis is a cornerstone for management of such patients, and rapid, accurate, and safe diagnostic techniques are critically important. Multiple diagnostic tools are available to clinicians. In addition to microscopy and culture, serodiagnosis and nucleic acid amplification techniques are emerging. Traditional and nontraditional methods are complementary, and judicious selection of tests in a given clinical setting is essential. This chapter reviews the diagnostic methods used in medical mycology and provides guidance to clinicians and laboratorians dealing with IFI in the transplant population.
Keywords: Antigen; Aspergillosis; Beta-D-glucan; Candidiasis; Culture; Diagnosis; Endemic mycoses; Galactomannan; Invasive fungal infections; Nucleic acid amplification technique

Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Dulek, Daniel E.; Mueller, Nicolas J.; Practice, on behalf of the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These guidelines from the AST Infectious Diseases Community of Practice review the diagnosis and management of pneumonia in the post-transplant period. Clinical presentations and differential diagnosis for pneumonia in the solid organ transplant recipient are reviewed. A two-tier approach is proposed based on the net state of immunosuppression and the severity of presentation. With a lower risk of opportunistic, hospital-acquired, or exposure-specific pathogens and a non-severe presentation, empirical therapy may be initiated under close clinical observation. In all other patients, or those not responding to the initial therapy, a more aggressive diagnostic approach including sampling of tissue for microbiological and pathological testing is warranted. Given the broad range of potential pathogens, a microbiological diagnosis is often key for optimal care. Given the limited literature comparatively evaluating diagnostic approaches to pneumonia in the solid organ transplant recipient, much of the proposed diagnostic algorithm reflects clinical experience rather than evidence-based data. It should serve as a template which may be modified according to local needs. The same holds true for the suggested empiric therapies, which need to be adapted to the local resistance patterns. Further study is needed to comparatively evaluate diagnostic and empiric treatment strategies in SOT recipients.
Keywords: diagnosis; pneumonia; transplantation

Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice - Eid, Albert J.; Ardura, Monica I.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
Clinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High-level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2-5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.
Keywords: human parvovirus B 19; intravenous immunoglobulin; post-transplant infection; solid organ transplantation

Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Fishman, Jay A.; Gans, Hayley; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO2 < 60 mm Hg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1 → 3) β-d-glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP-SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6-12 months post–transplant, preferably with TMP-SMX.
Keywords: antimicrobial; corticosteroid therapy; fungal; infection and infectious agents; pneumocystis jirovecii; pneumocystis pneumonia

Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Florescu, Diana F.; Schaenman, Joanna M.; Practice, on behalf of the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of adenovirus infections after solid organ transplantation. Adenovirus is an important cause of infectious complications in both stem cell transplant and SOT patients, causing a range of clinical syndromes including pneumonitis, colitis, and disseminated disease. The current update of the guidelines highlights that adenovirus surveillance testing should not be performed in asymptomatic recipients. Serial quantitative PCR might play a role in the decision to initiate or assess response to therapy in a symptomatic patient. The initial and most important components of therapy remain supportive care and decrease in immunosuppression. The use of antiviral therapy is not supported by prospective randomized clinical trials. However, intravenous cidofovir is considered the standard practice for treatment of severe, progressive, or disseminated adenovirus disease in most transplant centers. Intravenous immunoglobulin may be beneficial, primarily in a select group of patients with hypogammaglobulinemia. Future approaches to treatment of adenovirus disease may include administration of adenovirus-specific T-cell therapy.
Keywords: adenovirus; infection and infectious agents; infectious; solid organ transplant and transplantation

Candida Infections in Hematopoietic and Solid Organ Transplant Recipients - Freifeld, Alison G.; Kauffman, Carol A. (Principles and Practice of Transplant Infectious Diseases, 2019)
Infections caused by Candida species range from local mucous membrane involvement to widely disseminated disease. In patients who have received a hematopoietic cell or solid organ transplant, candidiasis is one of the most common infections that is seen and is often life threatening. Candida species are part of the normal human microbiota and, as such, rarely cause infection in healthy hosts. Infections arise when the organisms are able to proliferate locally and gain access to the bloodstream from their normal mucosal or cutaneous colonization niche. Candidemia and invasive candidiasis are directly attributable to a breakdown of normal barriers, such as that which occurs with candidemia related to a central venous catheter, or to impairment of host defenses, which is especially prominent with neutropenia. The most common species to cause infection is Candida albicans, but increasingly, Candida glabrata is reported, especially among patients who have hematological malignancies or have received a transplant. Treatment has improved in the last several decades with the availability of multiple azole and echinocandin agents, all of which are less toxic than amphotericin B. However, crude mortality rates for patients with candidemia remain high, reflecting in part the very ill patients who develop this infection. Increasing evidence shows that the sooner antifungal treatment is initiated, the better the outcome; thus, in patients at high risk for invasive candidiasis, empirical treatment is appropriate while awaiting diagnostic test results. Prophylaxis, generally with an azole agent, is given routinely to recipients of a hematopoietic cell transplant and to certain high-risk solid organ transplant recipients.
Keywords: Azoles; Candidemia; Candiduria; Central venous catheters; Echinocandins; Hepatosplenic candidiasis; Immunocompromised host; Lipid-formulation amphotericin B; Mucosal candidiasis

Epstein-Barr Virus Infection and Posttransplant Lymphoproliferative Disease - Gewurz, Benjamin E.; Moulton, Elizabeth; Bessnow, Amy; Weinstock, David M.; Bond, Sheila (Principles and Practice of Transplant Infectious Diseases, 2019)
Epstein-Barr virus (EBV) is an oncogenic herpesvirus with a worldwide seroprevalence of >90%. Like all members of the herpesvirus family, EBV establishes infection that persists for the lifetime of the host. In most healthy patients, both primary EBV infection and lifelong latent infection are benign. However, in an immunocompromised host, such as a transplant recipient, either primary infection or reactivation of latent infection can lead to severe disease. The most significant EBV-associated illness that occurs following solid-organ or hematopoietic stem cell transplantation is posttransplant lymphoproliferative disease (PTLD). In this chapter, we provide an overview of the virus, its life cycle, host immune control, diagnostic testing, and efforts at vaccine development. Particular focus is given to the clinical features, diagnosis, and management of EBV-associated PTLD.
Keywords: Acyclovir; Adoptive immunotherapy; Epstein-Barr virus; Ganciclovir; Herpesvirus; Posttransplant lymphoproliferative disease (PTLD); Rituximab

Infections in Intestinal and Multivisceral Transplantation - Girlanda, Raffaele; Timpone, Joseph G.; Soriano, Kevin M.; Fishbein, Thomas M. (Principles and Practice of Transplant Infectious Diseases, 2019)
Intestinal and multivisceral transplantation are associated with a significantly higher risk of infectious complications compared to other transplants. In this chapter we describe the approach to common infections after intestinal and multivisceral transplantation along with recent developments in the understanding of the gut microbiota and intestinal immune homeostasis.

Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Goldman, Jason D.; Julian, Kathleen (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of urinary tract infections (UTI) in solid organ transplantation, focusing on kidney transplant (KT) recipients. KT recipients have unique risk factors for UTI, including indwelling stents and surgical manipulation of the genitourinary tract. KT recipients experience multi-drug antibiotic-resistant infections—UTI prevention and management strategies must consider risks of antimicrobial resistance. Non-antimicrobial prevention strategies for UTI in KT recipients are reviewed. It is important to recognize that some renal transplant recipients with UTI may primarily present with fever, malaise, leukocytosis, or a non-specific sepsis syndrome without symptoms localized to the urinary tract. However, asymptomatic bacteriuria (AB) must be distinguished from UTI because AB is not necessarily a disease state. Accumulating data indicate that there are no benefits of antibiotics for treatment of AB in KT recipients more than 2 months after post-transplant. Further research is needed on management of AB in the early (<2 months) post-transplant period, prophylaxis for UTI in this era of antibiotic resistance, recurrent UTI, non-antimicrobial prevention of UTI, and uropathogens identified in donor urine and/or preservative fluid cultures.
Keywords: asymptomatic bacteriuria; cystitis; kidney transplantation; pyelonephritis; urinary tract infection; uropathogen

Intra-abdominal infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Haidar, Ghady; Green, Michael; Practice, the American Society of Transplantation Infectious Diseases Community of (Clinical Transplantation, 2019)
This new guideline from the AST IDCOP reviews intra-abdominal infections (IAIs), which cause substantial morbidity and mortality among abdominal SOT recipients. Each transplant type carries unique risks for IAI, though peritonitis occurs in all abdominal transplant recipients. Biliary infections, bilomas, and intra-abdominal and intrahepatic abscesses are common after liver transplantation and are associated with the type of biliary anastomosis, the presence of vascular thrombosis or ischemia, and biliary leaks or strictures. IAIs after kidney transplantation include renal and perinephric abscesses and graft-site candidiasis, which is uncommon but may require allograft nephrectomy. Among pancreas transplant recipients, duodenal anastomotic leaks can have catastrophic consequences, and polymicrobial abscesses can lead to graft loss and death. Intestinal transplant recipients are at the highest risk for sepsis, infection due to multidrug-resistant organisms, and death from IAI, as the transplanted intestine is a contaminated, highly immunological, pathogen-rich organ. Source control and antibiotics are the cornerstone of the management of IAIs. Empiric antimicrobial regimens should be tailored to local susceptibility patterns and pathogens with which the patient is known to be colonized, with subsequent optimization once the results of cultures are reported.
Keywords: Kidney transplant; abscess; anastomotic leak; bacteremia; biloma; cholangitis; intestinal transplant; kidney transplant; liver transplant; pancreas transplant; rejection

Parvovirus B19 - Hakki, Morgan; Strasfeld, Lynne (Principles and Practice of Transplant Infectious Diseases, 2019)
Parvovirus B19 was discovered in 1975, and the first reports associating B19 with human disease came 6 years later, when B19 was linked to cases of aplastic crisis in patients with sickle cell disease. Since then, B19 infection has become a recognized infectious complication in the immunocompromised host, including persons infected with human immunodeficiency virus (HIV), as well as solid organ (SOT) and hematopoietic cell transplant (HCT) recipients. While typically a benign, self-limited infection in immunocompetent hosts, B19 can have serious sequelae in the immunocompromised host. Fundamentals of disease pathogenesis, clinical manifestations, diagnosis, and treatment options are discussed.
Keywords: Parvovirus B19, Solid organ transplant, Hematopoietic cell transplant, Virus

Gastrointestinal Infections and Clostridium difficile Infection - Harold, Stephen; DuPont, Herbert L. (Principles and Practice of Transplant Infectious Diseases, 2019)
In recent years, extensive research and newer therapeutic strategies have remarkably reduced the number of acute and chronic rejections and graft-versus-host disease (GVHD) and have significantly improved the survival of transplant recipients. On the other hand, transplant recipients are more vulnerable to a wide range of infections as immunosuppressive therapies not only suppress host T-cell response but also destroy other rapidly dividing cells resulting in neutropenia and hypogammaglobulinemia. In the first 6 months following transplantation, gastrointestinal infections due to cytomegalovirus, herpes simplex virus, or Candida albicans are common. But, with prolonged and frequent hospital stay, long waiting times, advanced age, hypogammaglobulinemia, and systemic diseases like diabetes and renal insufficiency, the incidence of Clostridium difficile (C. difficile) infections (CDI) is on the rise and is the most commonly identified cause of enteric infections in liver transplant recipients. The changes in the incidence and severity of infection due to emergence of a hypervirulent strain of C. difficile bacteria and the associated healthcare cost represent a significant healthcare facility-associated public health problem. However, simple procedures such as environmental disinfection, hand hygiene, and other enteric precautions are very effective in minimizing the incidence of CDI. In this chapter, we present an overview of CDI as early diagnosis and prompt treatment strategies with newer drugs can help reduce morbidity and mortality due to CDI and eventually organ rejection and GVHD in this special population.
Keywords: Antibiotics; Clostridium difficile; Colonization; Diarrhea; Hypervirulence; Immunosuppression; Opportunistic; Pseudomembrane; Toxins

Infections in Heart, Lung, and Heart-Lung Transplantation - Henao-Martínez, Andrés F.; Montoya, José G. (Principles and Practice of Transplant Infectious Diseases, 2019)
Half a century has passed since the first orthotopic heart transplant took place. Surgical innovations allowed for heart, lung, and heart-lung transplantation to save lives of patients with incurable chronic cardiopulmonary conditions. The complexity of the surgical interventions, chronic host health conditions, and antirejection immunosuppressive medications makes infectious complications common. Infections have remained one of the main barriers for successful transplantation and a source of significant morbidity and mortality. Recognition of infections and its management in this setting require outstanding clinical skills since transplant recipients may not exhibit classic signs or symptoms of disease, and laboratory work has some pitfalls. The prevention, identification, and management of infectious diseases complications in this population are a priority to undertake to improve the medical outcomes of transplantation. Herein, we reviewed the historical aspects, epidemiology, and prophylaxis of infections in heart, lung, and heart-lung transplantation. We also discuss the most prevalent organisms affecting the host and the organ systems involved.
Keywords: Bacterial infections; Diagnosis; Epidemiology; Fungal infections; Heart transplantation; Heart-lung transplantation; Lung transplantation; Prophylaxis; Virus diseases

Antifungal Stewardship: A Practical Guide to Implementation - Hinckley, Catherine Chopp (2019)

BK polyomavirus in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Hirsch, Hans H.; Randhawa, Parmjeet S.; Practice, AST Infectious Diseases Community of (Clinical Transplantation, 2019)
The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non-kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV-DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV-DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV-associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy-proven BKPyV-associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV-DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine-A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV-DNAemia is definitively cleared, independent of failed allograft nephrectomy.
Keywords: BK virus; kidney; nephropathy; polyoma; transplantation

West Nile Virus in Immunocompromised Hosts - Ho, Dora Y.; Schaenman, Joanna M. D.; Baden, Lindsey R. (Principles and Practice of Transplant Infectious Diseases, 2019)
West Nile virus (WNV) is an emerging pathogen endemic in Africa and Europe. Recent events demonstrate the speed with which a vector-borne disease like WNV can disseminate when introduced into a susceptible, pathogen-naïve population, where competent reservoir and vectors are present. Since the arrival of WNV to the North American continent in 1999, it is estimated that 2–4 million people have been infected in the USA alone. It has special relevance to the immunocompromised host populations because of the possibility of WNV transmission through organ transplantation and the increased risk of neuroinvasive disease in immunocompromised patients. In this chapter a detailed discussion of WNV infection with a focus in transplant population is presented.
Keywords: Acute Flaccid Paralysis; Encephalitis; Hematopoietic Stem Cell Transplantation; Immunocompromised Hosts; Meningitis; Solid Organ Transplantation; West Nile virus

Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study - Hollyer, Ian; Varias, Francesca; Ho, Bing; Ison, Michael G. (Transplant Infectious Disease, 2019)
Background Recurrent urinary tract infections (UTI) are an important cause of morbidity and mortality in renal transplant recipients (RTR). Methods In this retrospective study we gathered clinical data from patients prescribed methenamine hippurate to prevent recurrent UTI pre- and post-intervention. Thirty-eight RTR ≥18 years old at Northwestern Memorial Hospital from 2006-2017 were included in the final analysis. Results The median and range for follow-up days were 365 (299-365) pre- vs 314 (105-365) post-methenamine. Total UTI frequency (9.16 vs 5.01/1000 patient follow-up days), days of antibiotic therapy to treat UTI (215 vs 132/1000 patient follow-up days), and hospitalization due to UTI (2.64 vs 1.07/1000 patient follow-up days) decreased while patients took methenamine. Escherichia coli and Klebsiella pneumoniae were the most commonly identified cause of UTI both pre- and post-intervention. Drug resistant bacteria (ESBL-producing or VRE) affected 3 patients pre- and recurred in 1 of those patients plus 3 new patients post-methenamine. Methenamine had few adverse side effects for patients. One patient had nausea and 1 was intolerant. Conclusion We found that methenamine is well tolerated and is useful in reducing UTI, antibiotic prescriptions, and hospitalization in RTR with recurrent UTI. Larger prospective studies are needed to confirm these findings.
Keywords: methenamine; renal transplant; urinary tract infection

Prevention of Fungal Disease - Huprikar, Shirish; Wingard, John R. (Principles and Practice of Transplant Infectious Diseases, 2019)
Invasive fungal infections are an important problem in the management of both solid organ and hematopoietic stem cell transplant recipients. This chapter summarizes the evidence and recommendations for preventing invasive fungal infections in transplant recipients. A summary of recommendations are presented in Table 64.1.
Keywords: Aspergillosis; Hematopoietic stem cell transplant; Invasive candidiasis; Kidney transplant; Liver transplant

Invasive Aspergillosis in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Husain, Shahid; Camargo, Jose F. (Clinical Transplantation, 2019)
These updated AST-IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid-organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post-transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12-week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non-lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.

Infections in Pediatric Transplant Recipients - Katragkou, Aspasia; O’Connor, Lucy; Roilides, Emmanuel; Walsh, Thomas J. (Principles and Practice of Transplant Infectious Diseases, 2019)
Infections are major complications in pediatric patients undergoing hematopoietic stem cell or solid organ transplantation. They also represent the most significant barrier to short- and long-term survival of the transplanted allograft. The achievements and advances during the past 30 years have resulted in remarkably improved outcome for pediatric patients undergoing transplantation. These advances in pediatric infectious disease supportive care have contributed substantially to the patients’ well-being and improved survival, alike. The immune defects and the possible etiologic agents for infection vary with the time elapsed since transplantation, a formal timetable for infectious complications after hematopoietic stem cell and solid organ transplantation forms the bases for an organized approach to assess a relevant differential diagnosis, treatment and management plan for these complex and severely immunosuppressed young transplant recipients. In this chapter a comprehensive review on epidemiology, clinical manifestations, and strategies for managing infectious diseases in pediatric transplant recipients is provided.
Keywords: Bacterial infections; Fungal infections; Hematopoietic stem cell transplantation; Pediatric transplant; Sold organ transplantation; Viral infections

Adaptive Immunotherapy for Opportunistic Infections - Katragkou, Aspasia; Walsh, Thomas J.; Roilides, Emmanuel (Principles and Practice of Transplant Infectious Diseases, 2019)
Infectious complications are a major cause of morbidity and mortality in patients undergoing solid organ or stem cell transplantation. Over the past years, advances in immunology and molecular biology have greatly contributed to a better understanding of the pathogenesis of opportunistic infections in the immunocompromised host. The lifelong immunosuppression required by the transplant recipients together with the limitations of the current anti-infective agents makes strategies able to stimulate immune response attractive aids to conventional treatment options. Among the immunotherapeutic strategies studied in transplant recipients aiming to enhance the adaptive immune response are the adoptive transfer of T lymphocytes and the use of cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), or interferon-gamma (IFN-γ). While some encouraging results in in vitro and in vivo studies exist, currently available clinical evidence on the use of these approaches is limited to allow firm recommendations.
Keywords: Cytokines; G-CSF; GM-CSF; IFN-γ; Infection; M-CSF; T-Cells; Transplantation

Human T-cell lymphotrophic virus in solid-organ transplant recipients: Guidelines from the American society of transplantation infectious diseases community of practice - Kaul, Daniel R.; Sharma, Tanvi S.; Practice, on behalf of the AST ID Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Human T-cell lymphotrophic virus 1 (HTLV)-1 in the pre- and post-transplant period. HTLV-1 is an oncogenic human retrovirus rare in North America but endemic in the Caribbean and parts of Africa, South America, Asia, and Oceania. While most infected persons do not develop disease, <5% will develop adult T-cell leukemia/lymphoma or neurological disease. No proven antiviral treatment for established HTLV-1 infection is available. The effect of immunosuppression on the development of HTLV-1-associated disease in asymptomatically infected recipients is not well characterized, and HTLV-1-infected individuals should be counseled that immunosuppression may increase the risk of developing HTLV-1-associated disease and they should be monitored post-transplant for HTLV-1-associated disease. Currently approved screening assays do not distinguish between HTLV-1 and HTLV-2, and routine screening of deceased donors without risk factors in low seroprevalence areas is likely to result in significant organ wastage and is not recommended. Targeted screening of donors with risk factors for HTLV-1 infection and of living donors (as time is available to perform confirmatory tests) is reasonable.
Keywords: complication: infectious; donors and donation: donor-derived infections; infection and infectious agents; viral: human T-lymphotropic virus

Respiratory Tract Diseases That May Be Mistaken for Infection - Kotloff, Robert M.; Dickey, Burton F.; Vander Els, Nicholas (Principles and Practice of Transplant Infectious Diseases, 2019)
The differential diagnosis of lung infiltrates in transplant patients includes non-infectious processes that may mimic pneumonia. Hydrostatic and non-cardiogenic pulmonary edema, as well as transfusion-related lung injury, may cause bilateral airspace opacification that may be confused with an infectious process. Chemotherapeutic agents, whether administered for treatment of an underlying hematologic malignancy, for induction prior to transplant, or for the treatment of GVHD or graft rejection after transplant, may cause lung injury that in some cases may not become apparent until years later. Radiation-induced lung injury may cause a distinct pattern of lung injury, which may present months after exposure. In hematopoietic stem cell transplant patients, pulmonary diagnoses such as engraftment syndrome, idiopathic pneumonia syndrome, and diffuse alveolar hemorrhage can mimic pneumonia. After lung transplantation, infiltrates may be seen as a consequence of primary graft dysfunction or allograft rejection. Organizing pneumonia may be seen both in recipients of solid organ and hematopoietic stem cell transplants. Organizing pneumonia may be cryptogenic or associated with the use of the mTOR inhibitor sirolimus. Failure to accurately diagnose non-infectious infiltrates may lead to unnecessary antibiotic treatment and failure to address the underlying pathophysiologic process.
Keywords: Infiltrate; Pneumonia; Pneumonitis; Radiographic; Radiologic

Travel and Transplantation - Kotton, Camille Nelson; Montoya, José G. (Principles and Practice of Transplant Infectious Diseases, 2019)
As organ transplant recipients live longer and healthier lives after transplant, they increasingly partake in foreign travel, for leisure, adventure, work, or to visit friends or relatives. A review of cohorts of transplant recipients shows that they tend to have minimal or suboptimal preparation prior to travel, with limited pre-travel vaccination, medications, and education, and overall poses greatly increased risk of travel-related infections and complications. Enhancing the knowledge of the transplant recipients is likely to result in better safety and outcomes for these vulnerable patients. This chapter covers optimal vaccination prior to travel, use of travel-related medications with information on drug interactions, specific educational topics, and details regarding additional resources.
Keywords: Malaria; Transplant; Travel; Tropical disease

Ventricular assist device-related infections and solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Koval, Christine E.; Stosor, Valentina; Practice, the AST ID Community of (Clinical Transplantation, 2019)
The Infectious Diseases Community of Practice of the American Society of Transplantation has published evidenced-based guidelines on the prevention and management of infectious complications in SOT recipients since 2004. This updated guideline reviews the epidemiology of ventricular assist device (VAD) infections and provides recommendations for the management and prevention of these infections. Almost one half of those awaiting heart transplantation are supported with VADs. Despite advances in device technologies, VAD infections commonly complicate mechanical circulatory support and remain typified by common components and anatomic locations. These infections have important implications for transplant candidates, most notably increased wait-list mortality. Strategic management of these infections is crucial for successful transplantation. Coincidentally, explantation of all VAD components at the time of transplantation is often the definitive cure for the device-associated infection. Highlighted in this updated guideline is the reported success of transplantation in patients with a variety of pre-existing VAD infections and guidance on post-transplant management strategies.
Keywords: bacteremia; device infection; driveline infection; ventricular assist device

Intestinal parasites including Cryptosporidium, Cyclospora, Giardia, and Microsporidia, Entamoeba histolytica, Strongyloides, Schistosomiasis, and Echinococcus: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - La Hoz, Ricardo M.; Morris, Michele I.; Practice, on behalf of the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of intestinal parasites in the pre- and post-transplant period. Intestinal parasites are prevalent in the developing regions of the world. With increasing travel to and from endemic regions, changing immigration patterns, and the expansion of transplant medicine in developing countries, they are increasingly recognized as a source of morbidity and mortality in solid-organ transplant recipients. Parasitic infections may be acquired from the donor allograft, from reactivation, or from de novo acquisition post-transplantation. Gastrointestinal multiplex assays have been developed; some of the panels include testing for Cryptosporidium, Cyclospora, Entamoeba histolytica, and Giardia, and the performance is comparable to conventional methods. A polymerase chain reaction test, not yet widely available, has also been developed to detect Strongyloides in stool samples. New recommendations have been developed to minimize the risk of Strongyloides donor-derived events. Deceased donors with epidemiological risk factors should be screened for Strongyloides and recipients treated if positive as soon as the results are available. New therapeutic agents and studies addressing the optimal treatment regimen for solid-organ transplant recipients are unmet needs.
Keywords: Cryptosporidium; Cyclospora; Cystoisospora; Echinococcus; Entamoeba histolytica; Giardia; Microsporidia; Parasites; Schistosoma; Strongyloides; donor-derived; transplant

Tissue and blood protozoa including toxoplasmosis, Chagas disease, leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in solid organ transplant recipients— Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - La Hoz, Ricardo M.; Morris, Michele I.; Transplantation, the Infectious Diseases Community of Practice of the American Society of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of tissue and blood protozoal infections in the pre- and post-transplant period. Significant new developments in the field have made it necessary to divide the previous single guideline published in 2013 into two sections, with the intestinal parasites separated from this guideline devoted to tissue and blood protozoa. The current update reflects the increased focus on donor screening and risk-based recipient monitoring for parasitic infections. Increased donor testing has led to new recommendations for recipient management of Toxoplasma gondii and Trypanosoma cruzi. Molecular diagnostics have impacted the field, with access to rapid diagnostic testing for malaria and polymerase chain reaction testing for Leishmania. Changes in Babesia treatment regimens in the immunocompromised host are outlined. The risk of donor transmission of free-living amebae infection is reviewed. Changing immigration patterns and the expansion of transplant medicine in developing countries has contributed to the recognition of parasitic infections as an important threat to transplant outcomes. Medications such as benznidazole and miltefosine are now available to US prescribers as access to treatment of tissue and blood protozoa is increasingly prioritized.
Keywords: Acanthamoeba; Babesia; Balamuthia; Leishmaniasis; Malaria; Naegleria; Parasites; Toxoplasma gondii; Trypanosoma cruzi; donor-derived; leishmaniasis; malaria; parasites; transplant

Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Lee, Dong H.; Zuckerman, Richard A.; Practice, on behalf of the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HSV in the pre- and post-transplant period. A majority of transplant recipients are seropositive for HSV-1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations. Acquisition from the donor is rare. Polymerase chain reaction is the preferred diagnostic test unless culture is needed for resistance testing. For limited mucocutaneous lesions, oral therapy can be used; however, in severe, disseminated, visceral or CNS involvement, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir-resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation. HSV-specific prophylaxis should be considered for all HSV-1 and HSV-2–seropositive organ recipients who are not receiving antiviral medication for CMV prevention that has activity against HSV.
Keywords: herpes simplex virus; prevention; transplantation; treatment; viral infection

Antibiotic prophylaxis for ureteral stent removal after kidney transplantation - Lee, Jennifer H.; Muthukumar, Thangamani; Kim, Jim; Aull, Meredith J.; Watkins, Anthony; Kapur, Sandip; Hartono, Choli (Clinical Transplantation, 2019)
There are no guidelines for antibiotic prophylaxis for ureteral stent removal after kidney transplantation. We reviewed the charts of 277 adult kidney transplant recipients with ureteral stents transplanted at our center between September 2014 and December 2015 and investigated whether antibiotic prophylaxis for stent removal was associated with reduced incidence of urinary tract infections (UTI). We defined UTI as a urine culture ≥104 CFU/mL of bacterial isolates irrespective of symptoms. Primary outcome was the incidence of UTI within four weeks of stent removal. Among the 277 recipients, 199 (72%) were on sulfamethoxazole/trimethoprim (SMZ/TMP) as Pneumocystis jirovecii prophylaxis. At the time of ureteral stent removal, 56 recipients (20%) received additional antibiotic prophylaxis (ABX+) and 221 (80%) did not (ABX-). The difference in the incidence of UTI in the ABX(+) group (16%) and ABX(−) group (19%) was not statistically significant (P = 0.85). Variables independently associated with the development of UTI were recipient age (odds ratio [OR] 1.04, [95% confidence interval 1.01-1.07]) and UTI while stents were in situ (OR 3.9 [2.00-7.62]). Use of SMZ/TMP was protective (OR 0.35 [0.18-0.7]). Our study does not show a statistically significant benefit for additional antibiotic prophylaxis for ureteral stent removal. Antibiotic prophylaxis may be beneficial for recipients not on SMZ/TMP at the time of stent removal.
Keywords: antibiotic prophylaxis; kidney transplant; ureteral stent

Marijuana use in transplantation: A call for clarity - Levi, Marilyn E.; Montague, Brian T.; Thurstone, Christian; Kumar, Deepali; Huprikar, Shirish S.; Kotton, Camille N. (Clinical Transplantation, 2019)
Transplant centers have varying policies for marijuana (MJ) use in donors, transplant candidates, and recipients. Rationales for these differences range from concerns for fungal complications, impaired adherence, and drug interactions. This paper reviews the current status of MJ policies and practices in transplant centers and results of a survey sent to the American Society of Transplantation (AST) membership by the Executive Committee of the AST Infectious Diseases Community of Practice.The purpose of the survey was to compare policies and concerns of MJ use to actual observed complications. Of the 3321 surveys sent, 225 members (8%) responded. Transplant centers varied in their approval processes, differing even in organ types within the same institutions. Furthermore, there was discordance among transplant centers in their perceived risks of marijuana use as opposed to complications actually observed. An increasing number of states continue to legalize medical and recreational MJ resulting in widespread availability. Further research is needed to assess the validity of concerns for complications of MJ use in potential donors and recipients. Ultimately, standardized guidelines should be established based on studies and evidence-based criteria to assist transplant programs in their policies around the use of cannabis in their donors and recipients.
Keywords: cannabis; marijuana; transplantation

Respiratory Viral Infections in Transplant Recipients - Liu, Catherine; Ho, Dora Y.; Boeckh, Michael (Principles and Practice of Transplant Infectious Diseases, 2019)
Respiratory viral infections (RVIs) are common among the general population; however, these often mild viral illnesses can lead to serious morbidity and mortality among recipients of hematopoietic stem cell and solid organ transplantation. The disease spectrum ranges from asymptomatic or mild infections to life-threatening lower respiratory tract infection or long-term airflow obstruction syndromes. Progression to lower respiratory tract infection or to respiratory failure is determined by the intrinsic virulence of the specific viral pathogen as well as various host factors, including the type of transplantation, status of the host’s immune dysfunction, the underlying disease, and other comorbidities. This chapter focuses on the epidemiology, clinical manifestations, diagnosis, and management of RVIs in this susceptible population and includes respiratory syncytial virus, parainfluenza virus, human metapneumovirus, influenza virus, human coronavirus, and human rhinovirus. The optimal management of these infections is limited by the overall paucity of available treatment, highlighting the need for new antiviral drug or immunotherapies.
Keywords: Human coronavirus; Human metapneumovirus; Human rhinovirus; Influenza virus; Parainfluenza virus; Respiratory syncytial virus; Transplantation

Ocular Infections in Transplant Patients - Lobo, Ann-Marie; Sobrin, Lucia; Durand, Marlene L. (Principles and Practice of Transplant Infectious Diseases, 2019)
Ocular infections in transplant patients can be rapidly progressive and result in significant vision loss and morbidity. Approximately 2% of transplant patients in several large series developed serious eye infections, and the most common were viral retinitis and fungal endophthalmitis. Viral retinitis is due to cytomegalovirus, herpes simplex, or herpes zoster. A particularly fulminant form of viral retinitis, progressive outer retinal necrosis, may occur and result in blindness within 1 to a few days. Hematogenous spread of bacterial and fungal infections to the eye may result in endophthalmitis. Ocular infections that occur in non-immunocompromised patients also occur in the transplant population, and these include keratitis (infection of the cornea), herpes zoster ophthalmicus, and ocular toxoplasmosis. Invasive fungal infections involving the orbit, such as rhinocerebral mucormycosis, are seen in transplant patients as they are in other immunocompromised patients. In transplant patients, sometimes the first signs of a life-threatening systemic infection occur in the eye. Patients with fungemia, for example, may present with vision loss from fungal endophthalmitis. Eye infections in the transplant population are important to diagnose promptly both to prevent irreversible vision loss, which may occur very quickly in the immunocompromised host, and to recognize an underlying systemic infection that may be life-threatening.
Keywords: Acute retinal necrosis; Chorioretinitis; Endophthalmitis; Keratitis; Mucormycosis; Ocular infection; Ocular toxoplasmosis; Ocular tuberculosis; Uveitis; Viral retinitis

Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Longworth, Sarah A.; Daly, Jennifer S.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre- and post-transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter-associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species-level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long-term multidrug regimens, and consideration of complex drug-drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.
Keywords: antibiotic; infection and infectious agents; nontuberculous mycobacteria; solid organ transplant

Screening of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Malinis, Maricar; Boucher, Helen W.; on behalf of the AST Infectious Diseases Community of Practice (Clinical Transplantation, 2019)
This updated section of the guideline from the Infectious Diseases Community of Practice of the American Society of Transplantation reviews the screening of donor and candidate prior to solid organ transplantation. Screening of donor and candidate is vital for optimizing post‐transplant outcomes. Risk assessment based on detailed history and appropriate diagnostic evaluation is essential. Serologic screening for certain viral infections is important and aids in immunization counseling and risk mitigation of recipients. In addition to serology, nucleic acid testing for hepatitis B, hepatitis C and human immunodeficiency virus has been required for deceased and living donors. Certain endemic exposure may warrant additional evaluation beyond recommended standard testing. Diagnosed infection in the donor or recipient warrants treatment as well as additional testing and/or prophylaxis to mitigate risk for posttransplant complications. Certain infections in the immediate pre‐transplant period may warrant delay of transplantation.

ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients - Martin-Loeches, Ignacio; Antonelli, Massimo; Cuenca-Estrella, Manuel; Dimopoulos, George; Einav, Sharon; De Waele, Jan J.; Garnacho-Montero, Jose; Kanj, Souha S.; Machado, Flavia R.; Montravers, Philippe; Sakr, Yasser; Sanguinetti, Maurizio; et al. (Intensive Care Medicine, 2019)
Introduction:  The term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs). Material and Methods:  In the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion. The task force used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the recommenda‑tions and assign levels of evidence. The recommendations and their strength were decided by consensus and, if nec‑essary, by vote (modified Delphi process). Descriptive statistics were used to analyze the results of the Delphi process. Statements obtaining > 80% agreement were considered to have achieved consensus. Conclusions:  The heterogeneity of this patient population necessitated the creation of a mixed working group comprising experts in clinical microbiology, infectious diseases and intensive care medicine, all chosen on the basis of their expertise in the management of IC and/or research methodology. The working group’s main goal was to provide clinicians with clear and practical recommendations to optimize microbiological diagnosis and treatment of IC. The Systemic Inflammation and Sepsis and Infection sections of the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) therefore decided to develop a set of recommendations for application in non-immunocompromised criti‑cally ill patients.

Successful treatment of Ureaplasma-induced hyperammonemia syndrome post-lung transplant - Matson, Kristine M.; Sonetti, David A. (Transplant Infectious Disease, 2019)
Hyperammonemia, in the absence of significant liver dysfunction, is an uncommon but often fatal occurrence following orthotopic lung transplant. Prior reports have provided evidence to support Ureaplasma species as an etiology for this syndrome. This case report describes an individual post-lung transplant, treated emperically with doxycycline along with other measures to lower ammonia levels, at the time hyperammonemia with encephalopathy was recognized. The patient clinically improved. Ureaplasma species were subsequently identified using 16S ribosomal RNA gene PCR/sequencing of pleural fluid, and by culture of bronchoalveolar (BAL) fluid. This case provides further support for empiric treatment of Ureaplasma species upon recognition of hyperammonemia syndrome post-lung transplant.
Keywords: Hyperammonemia; Ureaplasma; lung transplantation

Tests for latent tuberculosis in candidates for solid organ transplantation: A systematic review and meta-analysis - Maung Myint, Thida; Rogerson, Thomas E.; Noble, Kristy; Craig, Jonathan C.; Webster, Angela C. (Clinical Transplantation, 2019)
Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta-analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N = 7811), 12 studies compared IGRAs with TST directly, nine studies evaluated only TST and three studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55-6.48, IGRA: OR 2.78; 95%CI 1.55-5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85-5.73, IGRA: OR 3.85; 95%CI 2.16-6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10-9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with the presence of radiological evidence of previous TB.
Keywords: Latent tuberculosis; interferon gamma release assay; latent tuberculosis; solid organ transplantation; testing; tuberculin skin test

Intracranial, Spinal, and Paraspinal Infections in the Transplant Recipient - McCarthy, Matthew W.; Rosengart, Axel; Walsh, Thomas J. (Principles and Practice of Transplant Infectious Diseases, 2019)
Infections of the central nervous system (ICNS) contribute significantly to morbidity and mortality in patients receiving solid organ and stem cell transplants. The risk for ICNS is influenced by multiple factors, including the organ transplanted, type and degree of immunosuppression, post-transplant adverse events, as well as donor characteristics. These infections may be classified by anatomic location – intracranial, spinal, and paraspinal – as well as by time of onset. The early post-transplant period is generally defined as the first month after transplantation. Because the major effects of exogenous immunosuppression are not yet apparent, the causes of ICNS in this time period are those derived from either the donor or recipient and infectious complications of the transplant and hospitalization. In the period 1 to 6 months after transplantation, also known as the intermediate time period, the composition of the pathogens changes. Opportunistic infections prevail; however, there is geographic variation given the inter-institution variation in immunosuppressive and antimicrobial prophylaxis strategies. During the late time period, generally defined as more than 6 months after transplantation, most patients with good graft function receive stable and reduced levels of immunosuppression while continuing on some form of antimicrobial prophylaxis. The pathogens that cause CNS infection tend to more closely resemble the community-acquired pathogens responsible for these infections in immunocompetent hosts.
Keywords: Brain abscess; CNS infection; Encephalitis; Geographic variation; Immunosuppressive drugs; Meningitis; Post-transplant infection

Hepatitis A, B, and C - Merola, Jonathan; Jow, Alexander Z.; Sigal, Samuel H. (Principles and Practice of Transplant Infectious Diseases, 2019)
Viral hepatitis remains the leading cause of liver failure and is the primary indication for liver transplantation worldwide. Hepatitis viruses are categorized into five distinct subtypes that collectively render significant morbidity and mortality in transplanted patients. Each subtype has a distinct replication pattern, pathology, and treatment. While the primary pathology mediated by these viruses occurs within the liver, significant extrahepatic disease may be observed with particular subtypes of hepatitis and warrant special treatment modalities prior to and following transplantation. Advances in the management of hepatitis B and C have recently revolutionized the treatment paradigm from supportive care to cure. In this section, each hepatitis subtype is described separately and accompanied by diagnostic and treatment strategies with emphasis on care for the transplanted patient.
Keywords: Antiviral therapy; Hepatitis A virus; Hepatitis B virus; Hepatitis C virus; Liver; Transplant

Hepatobiliary Tract Infections - Merola, Jonathan; Mocharla, Robert M.; Jow, Alexander Z.; Sigal, Samuel H.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Infections involving the hepatobiliary tract contribute to significant morbidity and mortality in solid-organ transplant recipients, particularly recipients of a hepatic allograft. Bacteria within the gastrointestinal tract may colonize a dysfunctional biliary system, thereby increasing the risk for ascending cholangitis. Additionally, infections such as cytomegalovirus or Epstein-Barr virus may trigger life-threatening acute illness and foster risk for other opportunistic infections and malignancies, respectively during the posttransplant period. Fungal and protozoal pathogens may also find refuge within the biliary tract of immunosuppressed host, and approach toward such infections often requires a combined medical and surgical intervention. Screening for clinical, subclinical, and latent infections, early institution of prophylactic drug therapy, and appropriate immunization form the central tenet for evaluation of patients being considered for allograft transplantation. A high level of suspicion for biliary tract infections or infections involving the liver in at risk allograft recipients may assist in early diagnosis and prompt initiation of effective antimicrobial therapy. Risk mitigation by lowering drug-induced immune suppression, when possible, is important for effective management of such infections. In this chapter, a comprehensive review of hepatobiliary tract infections is presented with an emphasis on complications in patients undergoing solid-organ transplantation.
Keywords: Bacterial; Infection; Liver; Opportunistic infections; Transplant; Viral

Skin and Soft Tissue Infection in Transplant Recipients - Micheletti, Robert G.; Kovarik, Carrie L. (Principles and Practice of Transplant Infectious Diseases, 2019)
Transplant-related immunosuppression is an important risk factor for the development of infectious diseases. The skin, as barrier to the outside world and the body’s largest organ, is particularly susceptible to both primary and disseminated infection. For the astute and thorough clinician, the skin is a useful marker of the health of the patient. It may provide clues to systemic disease and offers a chance at early diagnosis and prompt intervention.
Keywords: Bacteria; Fungus; Immunosuppression; Opportunistic infection; Skin infection; Skin infestations; Transplant; Virus

Respiratory Tract Infections: Sinusitis, Bronchitis, and Pneumonia - Miko, Benjamin A.; Pereira, Marcus R.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Solid organ and hematopoietic stem cell transplant recipients are at increased risk of upper and lower respiratory tract infections. While these infections are frequently encountered in the general population, the spectrum of their clinical presentation including morbidity and mortality is increased in patients undergoing transplantation procedures. Impaired innate and adaptive immunity, potential anatomical abnormalities resulting from extensive surgical procedures, presences of indwelling medical devices, and increased healthcare exposure put transplant recipients at particularly high risk for respiratory tract disease. Infections of the respiratory tract can be divided into those affecting the paranasal sinuses, the upper airways such as bronchitis and tracheobronchitis, and the lower airways like pneumonia. Each of these clinical syndromes can further be classified based on their chronicity, acute vs. chronic; their setting, community vs. nosocomial; and the etiology such as bacteria, viruses, fungi, and rarely parasites. It is also important to realize that such immunologically vulnerable patients are at risk for polymicrobial infection that may present concurrently or in a sequential, consecutive fashion. This chapter reviews the common respiratory tract infections affecting transplant recipients with particular attention directed toward epidemiological risk factors, clinical presentations, diagnostic strategies, and common pathogens. Specific causes of opportunistic pneumonias are also reviewed.
Keywords: Bronchitis; Lower respiratory tract infection; Opportunistic disease; Pneumonia; Sinusitis; Upper respiratory tract infection

Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7) - Mikulska, Malgorzata; Cesaro, Simone; De Lavallade, Hugues; Di Blasi, Roberta; Einarsdottir, Sigrun; Gallo, Giuseppe; Rieger, Christina; Engelhard, Dan; Lehrnbecher, Thomas; Ljungman, Per; Cordonnier, Catherine (The Lancet Infectious Diseases, 2019)

Endemic fungal infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Miller, Rachel; Assi, Maha; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre- and post-transplant period. Though each of these endemic fungal infections has unique epidemiology and clinical manifestations, they all share a predilection for primary pulmonary infection and may cause disseminated infection, particularly in immunocompromised hosts. Culture remains the gold standard for definitive diagnosis, but more rapid diagnosis may be achieved with direct visualization of organisms from clinical specimens and antigen-based enzyme immunoassay assays. Serology is of limited utility in transplant recipients. The mainstay of treatment for severe infections remains liposomal amphotericin followed by a step-down azole therapy. Cases of mild to moderate severity with no CNS involvement may be treated with azole therapy alone. The newer generation azoles provide additional treatment options, but supported currently with limited clinical efficacy data. Azole therapy in transplant recipients presents a unique challenge owing to the drug-drug interactions with immunosuppressant agents. Therapeutic drug monitoring of azole levels is an essential component of effective and safe therapy. Infection prevention centers around minimizing epidemiological exposures, early clinical recognition, and azole prophylaxis in selected individuals.
Keywords: Antifungal; antifungal; azole; blastomycosis; coccidioidomycosis; fungal infection; histoplasmosis

Infections in Liver Transplantation - Mohanraj, B. Sharmila; Rangnekar, Amol S.; Timpone, Joseph G. (Principles and Practice of Transplant Infectious Diseases, 2019)
Liver transplantation has become an important treatment modality for patients with end-stage liver disease/cirrhosis, acute liver failure, and hepatocellular carcinoma. Although surgical techniques and immunosuppressive regimens for liver transplantation have improved significantly over the past 20 years, infectious complications continue to contribute to the morbidity and mortality in this patient population. The use of standardized screening protocols for both donors and recipients, coupled with targeted prophylaxis against specific pathogens, has helped to mitigate the risk of infection in liver transplant recipients. Patients with chronic liver disease and cirrhosis have immunological deficits that place them at increased risk for infection while awaiting liver transplantation. The patient undergoing liver transplantation is prone to develop healthcare-acquired infections due to multidrug-resistant organisms that could potentially affect patient outcomes after transplantation. The complex nature of liver transplant surgery that involves multiple vascular and hepatobiliary anastomoses further increases the risk of infection after liver transplantation. During the early post-transplantation period, healthcare-acquired bacterial and fungal infections are the most common types of infection encountered in liver transplant recipients. The period of maximal immunosuppression that occurs at 1–6 months after transplantation can be complicated by opportunistic infections due to both primary infection and reactivation of latent infection. Severe community-acquired infections can complicate the course of liver transplantation beyond 12 months after transplant surgery. This chapter provides an overview of liver transplantation including indications, donor-recipient selection criteria, surgical procedures, and immunosuppressive therapies. A focus on infections in patients with chronic liver disease/cirrhosis and an overview of the specific infectious complications in liver transplant recipients are presented.
Keywords: Acute liver failure; Antirejection drugs; Chronic hepatitis C infection; Deceased donor transplant; End-stage liver disease; Healthcare-acquired infections; Infectious complications of liver transplant; Living donor transplant; Opportunistic infections; Orthotopic liver transplant; Recurrence of viral hepatitis post-transplant

Infections in Kidney and Pancreas Transplantation - Morales, Megan K.; Cooper, Matthew; Abrams, Peter; Timpone, Joseph G. (Principles and Practice of Transplant Infectious Diseases, 2019)
The optimal treatment for patients with chronic kidney disease (CKD) requiring renal replacement therapy/dialysis is kidney transplantation. Additionally, pancreas transplantation alone or simultaneous pancreas-kidney transplantation offers improved quality of life as well as reversion or prevention of complications seen in patients with type 1 diabetes mellitus. Patients with CKD on dialysis are at increased risk for bacterial and blood-borne viral pathogens. During the initial first month posttransplantation period, kidney and kidney-pancreas transplant recipients are at increased risk for healthcare-acquired infections and complications associated with surgery. Over the next 6 months, during the period of maximal immunosuppression, these patients are at increased risk for opportunistic infections such as BK polyomavirus and cytomegalovirus. Anti-infective prophylactic strategies have been developed to decrease rates of specific opportunistic infections during this time period. Beyond 6 months, patients are at increased risk for community-acquired infections, including bacterial and fungal infections such as invasive molds, endemic mycoses, as well as the complications of chronic immunosuppressive therapy. This chapter provides a brief overview of kidney and pancreas transplantation with regard to types of transplantations, selection criteria, surgical procedures, and immunosuppressive regimens. It will then focus on infectious complications encountered in patients on dialysis and the pretransplantation evaluation for patients awaiting organs. Infectious complications that are specific to kidney and pancreas transplantation are reviewed in detail, including the role of anti-infective prophylaxis. Specific infectious etiologies and syndromes that are related to kidney and pancreas transplantation will also be presented.
Keywords: Antimicrobial prophylaxis; Chronic kidney disease; Donor-derived infections; Healthcare-acquired infections; Immunosuppressive therapy; Kidney transplant; Opportunistic infections; Pancreas transplant; Transplant evaluation; Urinary tract infection/pyelonephritis

Management of Clostridioides (formerly Clostridium) difficile infection (CDI) in solid organ transplant recipients: Guidelines from the American Society of Transplantation Community of Practice - Mullane, Kathleen M.; Dubberke, Erik R.; Practice, on behalf of the AST ID Community of (Clinical Transplantation, 2019)
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice address the prevention and management of Clostridium difficile infection in solid organ transplant (SOT) recipients. Clostridioides (formerly Clostridium) difficile infection (CDI) is among the most common hospital acquired infections. In SOT recipients, the incidence of CDI varies by type and number or organs transplanted. While a meta-analysis of published literature found the prevalence of postoperative CDI in the general surgical population to be approximately 0.51%, the prevalence of CDI that is seen in the solid organ transplant population ranges from a low of 3.2% in the pancreatic transplant population to 12.7% in those receiving multiple organ transplants. There are no randomized, controlled trials evaluating the management of CDI in the SOT population. Herein is a review and summary of the currently available literature that has been synthesized into updated treatment guidelines for the management of CDI in the SOT population.
Keywords: Antibiotic-associated diarrhea; Clostridium difficile; antibiotic-associated diarrhea; nosocomial infection; pseudomembranous colitis; solid organ transplant; solid-organ transplant

Vancomycin-resistant Enterococcus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Nellore, Anoma; Huprikar, Shirish; Practice, the AST ID Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation address vancomycin-resistant enterococci (VRE) infections in SOT candidates and recipients. VRE are an important cause of infection and have been named by the CDC as a serious public threat. Typically, a commensal of the gastrointestinal tract, VRE may become pathogenic after abdominal organ manipulation like transplantation. This guideline reviews the microbiology, antimicrobial resistance mechanisms, epidemiology, and clinical manifestations of VRE infection in the context of solid organ transplantation. Treatment regimens including combination therapies and novel investigational agents are also reviewed. Finally, an updated appraisal of infection control measures relevant to VRE infection and colonization is presented.
Keywords: Antibiotic Resistance; Enterococcus; Transplantation; antibiotic resistance; enterococcus; transplantation

Febrile Neutropenia in Transplant Recipients - Nesher, Lior; Rolston, Kenneth V. I. (Principles and Practice of Transplant Infectious Diseases, 2019)
Febrile neutropenic patients are at increased risk of developing infections. During the initial stages of neutropenia, most of these infections are bacterial. The spectrum of bacterial infections depends to some extent on whether or not patients receive antimicrobial prophylaxis when neutropenic. Since most transplant recipients do, Gram-positive organisms predominate, due to the fact prophylaxis is directed primarily against Gram-negative organisms. Staphylococcus species (often methicillin-resistant), Streptococcus species (viridans group streptococci, beta-hemolytic streptococci), and Enterococcus species (including vancomycin-resistant strains) are isolated most often. Therefore, potent empiric Gram-positive coverage is recommended by many in this setting. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella species are the most common Gram-negative pathogens isolated. Non-fermentative Gram-negative bacilli (Stenotrophomonas maltophilia, Acinetobacter species) are emerging as important pathogens. Many of these organisms acquire multiple mechanisms of resistance that render them multidrug resistant. The administration of prompt, broad-spectrum, empiric, antimicrobial therapy is essential and is generally based on local epidemiology and susceptibility/resistance patterns. Response rate to the initial regimen is generally in the range of 75–85%. Fungal infections develop in patients with prolonged neutropenia (greater than 7–10 days). Candida species and Aspergillus species are the predominant fungal pathogens, although many other fungi are opportunistic pathogens in this setting. Fungal infections are seldom documented microbiologically or on histopathology, and the administration of empiric antifungal therapy, when such infections are suspected, is the norm. Therapy is often prolonged, and outcomes are still suboptimal. The importance of infection control and antimicrobial stewardship cannot be overemphasized.
Keywords: Antimicrobial stewardship; Drug resistance; Empirical therapy; Febrile neutropenia; Multiple; Polymicrobial infections; Spectrum of infection; Stem cell transplantation

Human herpesvirus 6, 7, and 8 in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Pellett Madan, Rebecca; Hand, Jonathan; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HHV-6A, HHV-6B, HHV-7, and HHV-8 in the pre- and post-transplant period. The majority of HHV-6 (A and B) and HHV-7 infections in transplant recipients are asymptomatic; symptomatic disease is reported infrequently across organs. Routine screening for HHV-6 and 7 DNAemia is not recommended in asymptomatic patients, nor is prophylaxis or preemptive therapy. Detection of viral nucleic acid by quantitative PCR in blood or CSF is the preferred method for diagnosis of HHV-6 and HHV-7 infection. The possibility of chromosomally integrated HHV-6 DNA should be considered in individuals with persistently high viral loads. Antiviral therapy should be initiated for HHV-6 encephalitis and should be considered for other manifestations of disease. HHV-8 causes Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease and is also associated with hemophagocytic syndrome and bone marrow failure. HHV-8 screening and monitoring may be indicated to prevent disease. Treatment of HHV-8 related disease centers on reduction of immunosuppression and conversion to sirolimus, while chemotherapy may be needed for unresponsive disease. The role of antiviral therapy for HHV-8 infection has not yet been defined.

Infections in Allogeneic Stem Cell Transplantation - Pereira, Marcus R.; Pouch, Stephanie M.; Scully, Brian (Principles and Practice of Transplant Infectious Diseases, 2019)
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a widely used modality of therapy for a variety of malignant and nonmalignant diseases. Despite advances in pharmacotherapy and transplantation techniques, infection remains one of the most severe and frequently encountered complications of allo-HSCT.
Keywords: Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Bacterial, viral, fungal, and parasitic infections; Opportunistic infection; Preventative strategies; Vaccination

Methicillin-resistant Staphylococcus aureus in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Pereira, Marcus R.; Rana, Meenakshi M.; Practice, the AST ID Community of (Clinical Transplantation, 2019)
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of methicillin-resistant Staphylococcus aureus (MRSA) infections in solid organ transplantation. Despite an increasing armamentarium of antimicrobials active against MRSA, improved diagnostic tools, and overall declining rates of infection, MRSA infections remain a substantial cause of morbidity and mortality in solid organ transplant recipients. Pre- and post-transplant MRSA colonization is a significant risk factor for post-transplant MRSA infection. The preferred initial treatment of MRSA bacteremia remains vancomycin. Hand hygiene, chlorhexidine bathing in the ICU, central-line bundles that focus on reducing unnecessary catheter use, disinfection of patient equipment, and the environment along with antimicrobial stewardship are all aspects of an infection prevention approach to prevent MRSA transmission and decrease healthcare-associated infections.
Keywords: Methicillin-resistant Staphylococcus aureus; bacteremia; pneumonia; prevention; solid organ transplantation; treatment

Varicella zoster virus in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Pergam, Steven A.; Limaye, Ajit P.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, prevention, and management of varicella zoster virus (VZV) in the pre- and post-transplant period. Primary varicella is an uncommon complication post-solid-organ transplant (SOT), except among pediatric transplant patients and those seronegative for VZV. As the majority of SOT recipients are seropositive for VZV, herpes zoster (HZ) occurs frequently following SOT, particularly among recipients who are older (≥65 years of age) and those receiving more intensive immunosuppression. Transplant providers should aware of the increased risk for HZ-related complications such as dissemination, organ-specific involvement, and post-herpetic neuralgia. Treatment for localized zoster is primarily given as oral regimens, but those with more complicated presentations or those at risk for dissemination should be treated initially with IV therapy. Available antiviral prophylaxis regimens and vaccination strategies for varicella and HZ among these immunosuppressed patients remain a mainstay for prevention in the pre-and post-transplant periods. Finally, we discuss important approaches to addressing post-exposure prophylaxis and infection control practices for those SOT patients with documented VZV infections.
Keywords: Herpes Zoster; Transplantation; Varicella; herpes zoster; transplantation; varicella

Antimycobacterial Consideration in Transplantation Including Drug Non-susceptibility and Resistance: Tuberculosis and Nontuberculous Mycobacterial Disease - Philley, Julie V.; Griffith, David E. (Principles and Practice of Transplant Infectious Diseases, 2019)
Mycobacterial disease is commonly encountered during transplant evaluations and can be a major source of morbidity and mortality among transplant recipients. The impact of TB and NTM around the world has gained increased awareness, and the global impact of disease varies from country to country thus making mycobacterial epidemiology an important aspect of disease management. Risk factors for both tuberculosis (TB) and nontuberculous mycobacteria (NTM) must be assessed by transplant providers, and a low index of suspicion should warrant a prompt and accurate work-up to identify disease. Evaluation for active and latent TB is necessary prior to transplant. Preventing drug resistance for both TB and NTM plays a critical role in treatment options and outcomes. Adequate laboratory services are an essential component of drug regimens and often require reference laboratory assistance. Treatment regimens for mycobacterial disease require multiple antibiotics and frequently are associated with a host of drug-drug interactions. Knowledge of mycobacterial disease diagnosis, treatment regimens, and susceptibility patterns are essential to transplant evaluation and success.
Keywords: Latent; MTB; Mycobacteria; Mycobacterium; NTM; Nontuberculous; Solid organ; TB; Transplant; Tuberculosis

Nontuberculous Mycobacterial Disease in Transplant Recipients - Philley, Julie V.; Safdar, Amar; Daley, Charles L. (Principles and Practice of Transplant Infectious Diseases, 2019)
The spectrum of nontuberculous mycobacterial (NTM) infections has become an increasingly recognized cause of clinical concern in transplant recipients. While episodic isolation of NTM is often common among certain solid organ transplants such as lung recipients, there is sufficient evidence to support that serious infections can result in all transplant groups. As NTM are ubiquitous in the environment, and exposure to such bacteria is universally unavoidable, clinicians providing care for transplant populations must be up to date regarding the diagnosis and management of infections caused by NTM and maintain a high index of suspicion as clinical signs and symptoms may be insidious.
Keywords: Mycobacterium avium intracellulare; Nontuberculous Mycobacteria; Rapidly Growing Mycobacteria; Slowly Growing Mycobacteria

Multimodal safety assessment of measles-mumps-rubella vaccination after pediatric liver transplantation - Pittet, Laure F.; Verolet, Charlotte M.; McLin, Valérie A.; Wildhaber, Barbara E.; Rodriguez, Maria; Cherpillod, Pascal; Kaiser, Laurent; Siegrist, Claire-Anne; Posfay‐Barbe, Klara M. (American Journal of Transplantation, 2019)
Live-attenuated vaccines are currently contraindicated in solid-organ transplant recipients. However, the risk of vaccine-preventable infections is lifelong, and can be particularly severe after transplantation. In this prospective interventional national cohort study, 44 pediatric liver transplant recipients with measles IgG antibodies <150 IU/L (below seroprotection threshold) received measles-mumps-rubella vaccine (MMR) at a median of 6.3 years posttransplantation (interquartile range, 4.0 to 10.9). A maximum of two additional doses were administered in nonresponders or when seroprotection was lost. Vaccine responses occurred in 98% (95% confidence interval [CI], 88-100) of patients. Seroprotection at 1-, 2-, and 3-year follow-up reached 62% (95% CI, 45-78), 86% (95% CI, 70-95), and 89% (95% CI, 67-99), respectively. All patients responded appropriately to the booster dose(s). Vaccinations were well tolerated and no serious adverse event attributable to vaccination was identified during the 8-week follow-up period (or later), using a multimodal approach including standardized telephone interviews, diarized side effect reporting, and monitoring of vaccinal virus shedding. We conclude that live attenuated MMR vaccine can be administered in liver transplant recipients fulfilling specific eligibility criteria (>1 year posttransplantation, low immunosuppression, lymphocyte count ≥0.75 G/L), inducing seroprotection in most subjects. (Clinicaltrials.gov number NCT01770119).
Keywords: clinical research/practice; clinical trial; infection and infectious agents—viral; infectious disease; liver transplantation/hepatology; pediatrics; vaccine

Principles of Hematopoietic Stem Cell Transplantation - Poon, Michelle Limei; Champlin, Richard E.; Kebriaei, Partow (Principles and Practice of Transplant Infectious Diseases, 2019)
Hematopoietic stem cell transplantation (HSCT) refers to the process of intravenous infusion of self-renewing hematopoietic stem cells to restore normal hematopoiesis and is a rapidly developing and highly effective modality of treatment for a wide range of immunologic, metabolic, hematologic, as well as malignant diseases. Patients undergoing HSCT are at high risk of infectious complications in the peri-transplant period while awaiting immune reconstitution. There has been significant progress in this field, with improved supportive care, as well as development of novel reduced-intensity preparative regimens all of which have markedly reduced toxicities associated with this procedure and improved treatment outcomes. In addition, the use of alternative donor grafts, such as umbilical cord and haploidentical donors, allows more patients to have access to HSCT. This chapter aims to provide a broad overview of HSCT, reviewing both the historical aspects and the underlying immunobiology of this procedure. In addition, technical aspects of HSCT, latest advances in the field and an overview of the relevant literature, and clinical issues faced in practice are also discussed.
Keywords: Allogeneic hematopoietic stem cell transplantation; Autologous

Tuberculosis - Portal-Celhay, Cynthia; Philips, Jennifer A. (Principles and Practice of Transplant Infectious Diseases, 2019)
This chapter will review the basic biology of Mycobacterium tuberculosis and then focus on the epidemiology, clinical manifestations, and diagnosis in transplant patients. Prevention and treatment will be considered elsewhere. Tuberculosis (TB) remains a leading cause of human mortality in resource-limited settings, in part because it is still a diagnostic and treatment challenge. These challenges are compounded in immunocompromised hosts such as transplant patients because the performance of diagnostic tests is poor, the clinical presentation is often atypical, and treatment is complicated by toxicity and drug-drug interactions. While there have been significant recent advances in our understanding of bacterial pathogenesis and host responses, the picture remains incomplete. Conventional tuberculin skin testing, acid-fast bacilli smear, mycobacterial culture, and antibiotic sensitivity testing are imperfect tools. New molecular techniques improve the speed and certainty with which a diagnosis can be made, but little data exist on their use in the transplant patient. The prevalence of TB is low in the countries that have historically had access to organ transplantation. However, immigration to such countries and the expansion of transplants to countries with higher incidences of TB have made tuberculosis an increasingly important posttransplant complication. When tuberculosis does happen in transplant patients, the morbidity and mortality are substantial.
Keywords: Granuloma; Interferon-γ release assays (IGRAs); Latent infection; Mycobacterium bovis-bacillus Calmette-Guerin (BCG); Mycobacterium tuberculosis; Tuberculin skin test (TST); Tuberculosis

Multidrug-resistant Gram-negative bacterial infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Pouch, Stephanie M.; Patel, Gopi; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug-resistant (MDR) Gram-negative bacilli in the pre- and post-transplant period. MDR Gram-negative bacilli, including carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram-negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram-negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram-negative pathogens, especially in the setting of organ transplantation.
Keywords: Gram-negative bacterial infection; Multidrug-resistance; multidrug resistance; post-transplant infection; solid organ transplantation

Herpes Simplex Viruses 1 and 2, Varicella Zoster Virus, and Human Herpes Viruses 6, 7, and 8 in Transplant Recipients - Razonable, Raymund R. (Principles and Practice of Transplant Infectious Diseases, 2019)
Human herpes viruses are a family of double-stranded DNA viruses that cause opportunistic infections in solid organ and hematopoietic stem cell transplant recipients. Alpha-herpesviruses cause localized ulcerative mucosal and vesicular cutaneous lesions, with the tendency to disseminate if not treated early and aggressively. Beta-herpes viruses, discussed in this chapter such as human herpes viruses 6 and 7, may rarely cause a febrile illness and a skin rash; however, HHV6 in recipients of allogeneic HSCT is well recognized to cause serious illness including viral hepatitis, encephalitis, and myelosuppression including loss of stem cell graft. The gamma-herpesvirus, HHV-8, causes Kaposi’s sarcoma and body cavity lymphoma, among other rare diseases mostly seen in patients with HIV/AIDS. This chapter will review the epidemiology, clinical diseases, diagnosis, prevention, and treatment of six of the eight members of the human herpesvirus family, including HSV-1, HSV-2, VZV, HHV-6A and HHV-6B, HHV-7, and HHV-8.
Keywords: Herpes; Kaposi’s sarcoma; Lymphoma; Ulcers; Varicella; Zoster

Cryptococcus Infections in Transplant Recipients - Razonable, Raymund R.; Chong, Pearlie P. (Principles and Practice of Transplant Infectious Diseases, 2019)
Cryptococcosis is the third most common invasive fungal infection among solid organ transplant recipients but has been reported very rarely in hematopoietic stem cell transplant recipients. Pulmonary cryptococcal disease is the most common clinical presentation, and the central nervous system involvement is the most common extrapulmonary site. Diagnosis is confirmed by isolation of the fungus from culture samples and measuring cryptococcal antigen in various body fluids including serum and CSF; histologic evidence of dimorphic fungi in tissue samples may provide a clue to the etiology and in most instances is not required to confirm the diagnosis. Depending on disease severity and extent of infection, treatment consists of lipid formulations of amphotericin B plus flucytosine, and/or fluconazole. Reduction in immunosuppression should also be attempted in transplant recipients with acute cryptococcal infection. However, attempts in rapid reduction of immune suppression may theoretically place patients at risk for cryptococcal immune reconstitution inflammatory syndrome. In this chapter, a comprehensive review of cryptococcal disease is presented in context of patients undergoing solid organ and hematopoietic stem cell transplantation.
Keywords: Cryptococcosis; Fluconazole; Immune reconstitution; Meningitis; Transplantation

Cytomegalovirus in solid organ transplant recipients—Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice - Razonable, Raymund R.; Humar, Atul (Clinical Transplantation, 2019)
Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation Infectious Diseases Community of Practice provides evidence-based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug-resistant CMV infection are presented. There is an increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.
Keywords: cidofovir; cytomegalovirus; foscarnet; transplantation; valganciclovir

Nocardia infections in solid organ transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation - Restrepo, Alejandro; Clark, Nina M.; Transplantation, on behalf of the Infectious Diseases Community of Practice of the American Society of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation (SOT). Nocardia infections have increased in the last two decades, likely due to improved detection and identification methods and an expanding immunocompromised population. The risk of developing nocardiosis after transplantation varies with the type of organ transplanted and the immunosuppression regimen used. Nocardia infection most commonly involves the lung. Disseminated infection can occur, with spread to the bloodstream, skin, or central nervous system. Early recognition of the infection and initial appropriate treatment is important to achieve good outcomes. Species identification and antimicrobial susceptibility testing are strongly recommended, as inter- and intraspecies susceptibility patterns can vary. Sulfonamide is the first-line treatment of Nocardia infections, and combination therapy with at least two antimicrobial agents should be used initially for disseminated or severe nocardiosis. Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis may be helpful in preventing Nocardia infection after SOT.
Keywords: brain abscess; immunocompromised patients; nocardiosis; opportunistic infection; pneumonia