Once-Daily Foscarnet Is Effective for Human Herpesvirus 6 Reactivation after Hematopoietic Stem Cell Transplantation - Vittayawacharin, Pongthep; E'Leimat, Ghayda'; Lee, Benjamin J.; Griffin, Shawn; Doh, Jean; Nam, Hannah; Blodget, Emily; Jeyakumar, Deepa; Kongtim, Piyanuch; Ciurea, Stefan O. (Transplantation and Cellular Therapy, 2023)
Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age 18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the ﬁrst 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamidebased graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at ﬁrst reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients.

Risk of progression to active tuberculosis for indeterminate interferon-gamma release assay in immunocompromised individuals: a systematic review and meta-analysis - Zhou, Guozhong; Luo, Shiqi; He, Jian; Chen, Nan; Zhang, Yu; Cai, Shunli; Guo, Xin; Song, Chao (Clinical Microbiology and Infection, 2023)

Risk factors for BK virus‐associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A systematic review and meta‐analysis - Zhou, Xuemei; Zhang, Senlin; Fan, Junjie; Zhu, Xiaoping; Hu, Shaoyan (Clinical Transplantation, 2023)
Abstract Objective and Background BK virus‐associated hemorrhagic cystitis (BKV‐HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo‐HCT) recipients. Therefore, identifying the potential risk factors of BKV‐HC after allo‐HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV‐HC remain debatable. Therefore, we conducted a systematic review and meta‐analysis to identify the risk factors for BKV‐HC, for early prevention of the occurrence of BKV‐HC and to improve the quality of life and prognosis of allo‐HCT recipients. Methods We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV‐HC. Results Overall, 11 studies involving 2556 allo‐HCT recipients were included in this meta‐analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07–1.62; p = .009, I 2 = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18–2.87; p = .007, I 2 = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36–2.28; p < .0001, I 2 = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02–3.69; p < .0001, I 2 = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12–2.60; p = .01, I 2 = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12–8.78; p = .03, I 2 = 79%) were significantly associated with BKV‐HC in the univariable analysis. Conclusions Our meta‐analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV‐HC.

Therapeutic drug monitoring following crushed administration of delayed-release posaconazole tablets via enteral feeding tubes - Stevens, Ryan W; O’Connell, Casey; Huang, Angie; Epps, Kevin L; Ilges, Dan (Journal of Antimicrobial Chemotherapy, 2022)
Posaconazole, a triazole antifungal commonly used for the treatment and prevention of invasive fungal infections, is available in IV, oral suspension and oral delayed-release (DR) tablet formulations.1–3 Of the oral formulations, the DR tablet is favoured owing to its superior bioavailability, once-daily dosing and reliable absorption regardless of gastric acidity.4 Even when dosed appropriately, posaconazole oral solution often does not achieve therapeutic levels.5 This complicates administration in patients unable to swallow tablets whole and in whom long-term IV administration is undesirable. Posaconazole DR tablets are labelled as ‘do not crush,’ largely due to extrapolated concern that crushing the DR matrix may lead to a ‘dose dump’ and altered bioavailability.6,7 Recently, several case series have demonstrated success with crushing and administering the DR tablets via enteral feeding tubes, thus prompting a practice change across our health system.8–10

Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis - Manesh, Abi; Devasagayam, Emily; Bhanuprasad, Kundakarla; Mathew, Sumith K.; Karthik, Rajiv; Mathew, Binu S.; Varghese, George M. (Antimicrobial Agents and Chemotherapy, 2022)
A signiﬁcant proportion of patients with Rhino-orbito-cerebral mucormycosis (ROCM) develop oroantral ﬁstulas. Due to the unclear efﬁcacy of crushed delayed-release posaconazole tablets (DRPT) via nasogastric tube in this group of patients, clinicians often use inferior alternatives like posaconazole suspension. In this prospective study, we report good plasma concentrations (median, 2,639 ng/mL; interquartile range [IQR], 1,690 to 3,575 ng/mL; and range, 1,004 to 4,835ng/mL) and complete cure and survival at 3 and 6 months in 19 such patients.

Risks of Infectious Disease in Xenotransplantation - Fishman, Jay A. (New England Journal of Medicine, 2022)

Tuberculosis treatment without rifampin in kidney/kidney–pancreas transplantation: A case series report - Radisic, Marcelo Victor; Pujato, Natalia Rosana; Bravo, Pablo Martin; del Grosso, Roxana Constanza; Hunter, Martin; Beltramino, Santiago; Linares González, Laura; Cornet, María Lucía; del Carmen Rial, Maria; Franzini, Rosa Livia; Dotta, Ana C.; León, Luis Roberto; et al. (Transplant Infectious Disease, 2022)
Background: The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney–pancreas transplantation.

Solid organ transplant recipients with tuberculosis disease in California, 2010 to 2020 - Katrak, Shereen; Han, Emily; Readhead, Adam; Fung, Monica; Keh, Chris; Flood, Jennifer; Barry, Pennan (American Journal of Transplantation, 2022)
Keywords: AFB; CT; IGRA; LTBI; NAAT; Organ Procurement and Transplantation Network (OPTN); RVCT; Reports of Verified Case of Tuberculosis; SOT; TB; TST; UNOS; acid-fast bacilli; clinical research/practice; computerized tomography; donors and donation: donor-derived infections; health services and outcomes research; infection; infections of immune-compromised; infectious disease; interferon gamma release assay; latent tuberculosis infection; lung transplantation/pulmonology; mycobacterial; nucleic acid amplification test; organ transplantation; solid organ transplantation; tuberculin skin test; tuberculosis; united network for organ sharing

How I Prevent Viral Reactivation in High-risk Patients - Dadwal, Sanjeet Singh; Papanicolaou, Genovefa; Boeckh, Michael (Blood, 2022)
Preventing viral infections at an early stage is a key strategy of successfully improving transplant outcomes. Preemptive therapy and prophylaxis using antiviral agents have been used successfully to prevent clinically significant viral infections in hematopoietic cell transplant (HCT) recipients. Major progress has been made over the past decades in preventing viral infections through a better understanding of the biology and risk factors as well as the introduction of novel antiviral agents and advances in immunotherapies. High quality evidence exists for the effective prevention for herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) infection and disease. Fewer data are available on the effective prevention of human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), Adenovirus (ADV) and BK virus infections. To highlight the spectrum of clinical practice, here we review high-risk situations that we handle with a high degree of uniformity, and cases that feature differences in approaches, reflecting distinct HCT practices such as ex-vivo T cell depletion.

Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022) - Dioverti, Veronica; Boghdadly, Zeinab El; Shahid, Zainab; Waghmare, Alpana; Abidi, Maheen Z.; Pergam, Steven; Boeckh, Michael; Dadwal, Sanjeet; Kamboj, Mini; Seo, Susan; Chemaly, Roy F.; Papanicolaou, Genovefa A. (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2022)
Keywords: COVID-19; Cellular therapy; Hematopoietic cell transplantation; SARS-CoV-2; cellular therapy; hematopoietic cell transplantation

Liposomal amphotericin B—the present - Maertens, J; Pagano, L; Azoulay, E; Warris, A (Journal of Antimicrobial Chemotherapy, 2022)
Most invasive fungal infections are opportunistic in nature but the epidemiology is constantly changing, with new risk groups being identified. Neutropenia is a classical risk factor for fungal infections, while critically ill patients in the ICU are now increasingly at risk of yeast and mould infections. Factors to be considered when choosing antifungal treatment include the emergence of rarer fungal pathogens, the risk of resistance to azoles and echinocandins and the possibility of drug–drug interactions. Liposomal amphotericin B has retained its place in the therapeutic armamentarium based on its clinical profile: a broad spectrum of antifungal activity with a low risk of resistance, predictable pharmacokinetics with a rapid accumulation at the infection site (including biofilms), a low potential for drug–drug interactions and a low risk of acute and chronic treatment-limiting toxicities versus other formulations of amphotericin B. It is a suitable choice for the first-line empirical or pre-emptive treatment of suspected fungal infections in neutropenic haematology patients and is an excellent alternative for patients with documented fungal disease who can no longer tolerate or continue their first-line azole or echinocandin therapy, both in the haematology setting and in the ICU. Moreover, it is the first-line drug of choice for the treatment of invasive mucormycosis. Finally, liposomal amphotericin B is one of the few antifungal agents approved for use in children of all ages over 1 month and is included in paediatric-specific guidelines for the management of fungal disease.

Impact of Cytomegalovirus Replication in Patients with Aggressive B Cell Lymphoma Treated with Chimeric Antigen Receptor T Cell Therapy - Márquez-Algaba, Ester; Iacoboni, Gloria; Pernas, Berta; Esperalba, Juliana; Los Arcos, Ibai; Navarro, Victor; Monforte, Arnau; Beas, Francisco; Albasanz-Puig, Adaia; Carpio, Cecilia; Barba, Pere; Ruiz-Camps, Isabel (Transplantation and Cellular Therapy, 2022)
Data are scarce on cytomegalovirus (CMV) replication in patients receiving CD19-directed chimeric antigen receptor (CAR) T cell treatment. Here we describe the incidence, severity, and management of CMV infection in patients with aggressive B cell lymphoma treated with CAR T cell therapy. In this retrospective observational study, we analyzed CMV viral load and its clinical impact in patients with aggressive B cell lymphoma receiving CAR T cell therapy between July 2018 and December 2021 at a single center. Patients with a negative baseline CMV IgG or a previous allogeneic stem cell transplantation were excluded. CMV replication was determined in whole blood. Overall, 105 patients met the study's inclusion criteria. Ten patients presented with CMV replication before CAR T cell infusion and were analyzed separately. Forty-two of the remaining 95 patients (44%) had at least 1 positive CMV determination, with a viral load ≥1000 IU/mL in 21 patients (22%). Four patients in the main cohort (N = 95) and 4 patients in the preinfusion replication group (N = 10) achieved a viral load >10,000 IU/mL. Only 7 patients received preemptive antiviral treatment. No CMV end-organ disease was reported. The sole independent risk factor associated with CMV viremia ≥1000 IU/mL was dexamethasone treatment (odds ratio, 8.4; 95% confidence interval, 2.4 to 36.6; P = .002). Based on our findings, we designed an algorithm for CMV management in this setting. CMV replication is relatively frequent in patients with aggressive B cell lymphoma receiving CAR T cell therapy. It is usually self-limited and not associated with end-organ disease. Patients receiving dexamethasone or harboring CMV replication before infusion might benefit from active surveillance and preemptive treatment strategies.
Keywords: Aggressive B cell lymphoma; CAR T cell therapy; Cytomegalovirus replication; Cytomegalovirus surveillance

Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial - Thompson, George R.; Soriano, Alex; Cornely, Oliver A.; Kullberg, Bart Jan; Kollef, Marin; Vazquez, Jose; Honore, Patrick M.; Bassetti, Matteo; Pullman, John; Chayakulkeeree, Methee; Poromanski, Ivan; Dignani, Cecilia; et al. (The Lancet, 2022)

ISHLT/AST/ASTS Joint Statement about COVID-19 Vaccination in Organ Transplant Candidates and Recipients (2022)

Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient - Teitelbaum, Daniel; Elligsen, Marion; Katz, Kevin; Lam, Philip W; Lo, Jennifer; MacFadden, Derek; Vermeiren, Christie; Daneman, Nick (Clinical Infectious Diseases, 2022)
Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients.Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type.Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals.Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.

The Geographic Distribution of Dimorphic Mycoses in the United States for the Modern Era - Mazi, Patrick B; Sahrmann, John M; Olsen, Margaret A; Coler-Reilly, Ariella; Rauseo, Adriana M; Pullen, Matthew; Zuniga-Moya, Julio C; Powderly, William G; Spec, Andrej (Clinical Infectious Diseases, 2022)
The dimorphic mycoses (DM) of the United States, Histoplasma, Coccidioides, and Blastomyces, commonly known as endemic mycoses of North America (in addition to Paracoccidioides), are increasingly being diagnosed outside their historical areas of endemicity. Despite this trend, the maps outlining their geographical distributions have not been updated in more than half a century using a large, nationwide database containing individual patient-level data.Retrospective analysis of >45 million Medicare fee-for-service beneficiaries from 1 January 2007 through 31 December 2016. Diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were defined by International Classification of Diseases 9th/10th edition codes. Primary outcome was the incidence of histoplasmosis, coccidioidomycosis, and blastomycosis for each US county. Clinically meaningful thresholds for incidence were defined as 100 cases per 100,000 person-years cases for histoplasmosis and coccidioidomycosis and 50 cases for blastomycosis.There were 79,749 histoplasmosis, 37,726 coccidioidomycosis, and 6,109 blastomycosis diagnoses in unique persons from 2007-2016 across 3,143 US counties. Considering all US states plus Washington DC, 94% (48/51) had at least one county above the clinically relevant threshold for histoplasmosis, 69% (35/51) for coccidioidomycosis, and 78% (40/51) for blastomycosis.Persons with histoplasmosis, coccidioidomycosis, and blastomycosis are diagnosed in significant numbers outside their historical geographic distributions established more than 50 years ago. Clinicians should consider DM diagnoses based on compatible clinical syndromes with less emphasis placed on patient’s geographic exposure. Increased clinical suspicion leading to a subsequent increase in DM diagnostic testing would likely result in fewer missed diagnoses, fewer diagnostic delays, and improved patient outcomes.

Voriconazole Therapeutic Drug Monitoring and Hepatotoxicity in Critically Ill Patients: A Nationwide Multicenter Retrospective Study - Wang, Taotao; Miao, Liyan; Shao, Hua; Wei, Xiaohua; Yan, Miao; Zuo, Xiaocong; Zhang, Jun; Hai, Xin; Fan, Guangjun; Wang, Wei; Hu, Linlin; Zhou, Jian; et al. (International Journal of Antimicrobial Agents, 2022)
Objectives The aim of this study was to characterize voriconazole trough concentrations (Cmin) and associated hepatotoxicity, and to determine predictors of hepatotoxicity and identify high-risk groups in critically ill patients. Methods This was a nationwide, multicenter, retrospective study. We studied Cmin and hepatotoxicity in 363 critically ill patients from 2015 to 2020 who received voriconazole treatment. Logistic regression and classification and regression tree (CART) models were used to identify the high-risk patients. Results A large interindividual variability was observed in the voriconazole initial Cmin and concentrations ranging from 0.1 mg/L to 18.72 mg/L. Voriconazole-related grades ≥2 hepatotoxicity developed in 101 patients, including 48 patients with grades ≥3 hepatotoxicity. The median time to hepatotoxicity occurrence was 3 days (range 1–24 days), and 83.2% of hepatotoxicity cases occurred within 7 days after voriconazole initiation. Voriconazole Cmin was significantly associated with hepatotoxicity. The CART model showed that the significant predictors of grades ≥2 hepatotoxicity were Cmin >3.42 mg/L, receiving trimethoprim-sulfamethoxazole or tigecycline treatment simultaneously, and suffering from sepsis shock. The model predicted that grades ≥2 hepatotoxicity incidence among these high-risk patients was 48.3–63.4%. The significant predictors of grades ≥3 hepatotoxicity were Cmin >6.87 mg/L, concomitating use of ≥3 hepatotoxic drugs, and complicating with sepsis shock, and the predictive incidence among these high-risk patients was 22.7–36.8%. Conclusion Patients with higher voriconazole Cmin and sepsis shock, as well as concomitant use of hepatotoxic drugs were the strongest predictors of hepatotoxicity. Voriconazole plasma concentration monitoring should be performed early to avoid hepatotoxicity.
Keywords: Hepatotoxicity; Trough concentrations, Critically ill patients; Voriconazole

People at Risk - People with Weakened Immune Systems | Listeria | CDC - CDC (2022)

Routine Donor and Recipient Screening for Mycoplasma hominis and Ureaplasma Species in Lung Transplant Recipients - Vijayvargiya, Prakhar; Esquer Garrigos, Zerelda; Kennedy, Cassie C; Daly, Richard C; Wylam, Mark E; Patel, Robin; Beam, Elena (Open Forum Infectious Diseases, 2022)
Background Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum may cause post-transplant infections in lung transplant recipients. We evaluated routine pretransplant screening for these Mollicutes. Methods We retrospectively reviewed records of lung transplant recipients at our tri-site institution from 01/01/2015 to 11/15/2019. M. hominis and/or Ureaplasma polymerase chain reaction (PCR) was performed on pretransplant recipient urine specimens and donor bronchial swabs at the time of transplantation. Development of Mollicute infection and hyperammonemia syndrome (HS) was recorded. Results A total of 268 patients underwent lung transplantation during the study period, of whom 105 were screened with at least 1 Mollicute PCR. Twelve (11%) screened positive; 10 donors, 1 recipient, and 1 both. Among positive donors, 3 were positive for M. hominis, 5 for U. urealyticum, and 4 for U. parvum. Preemptive therapy included doxycycline, levofloxacin, and/or azithromycin administered for 1–12 weeks. Despite therapy, 1 case of M. hominis mediastinitis and 1 case of HS associated with Ureaplasma infection occurred, both donor-derived. Of those screened before transplant, cases with positive screening were more likely (P < 0.05) to develop Mollicute infection despite treatment (2/12, 17%) than those who screened negative (1/93, 1%). Conclusions Pretransplant recipient urine screening had a low yield and was not correlated with post-transplant Mollicute infection, likely because most M. hominis and U. parvum/urealyticum infections in lung transplant recipients are donor-derived. Routine donor bronchus swab PCR for M. hominis, U. urealyticum, and U. parvum followed by preemptive therapy did not obviously impact the overall incidence of Mollicute infection or HS in this cohort.

Infections Simulating Immune Checkpoint Inhibitor Toxicities: Uncommon and Deceptive - Gudiol, Carlota; Hicklen, Rachel S; Okhyusen, Pablo C; Malek, Alexandre E; Kontoyiannis, Dimitrios P (Open Forum Infectious Diseases, 2022)
Abstract Use of immune checkpoint inhibitors (ICIs), a revolutionary treatment in modern oncology, is frequently complicated by immune-related adverse events (irAEs), which can be confused with infections, and vice versa, thus complicating management decisions. In this study, we review the published cases of infections as simulators of irAEs in cancer patients.

Comparison of Indirect Fungal Diagnostic Tests in Patients With Proven Histoplasmosis - Krishnan, Gayathri; Power, Margaret; Bariola, J Ryan; Dare, Ryan (Open Forum Infectious Diseases, 2022)
Abstract Background Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-Histoplasma fungal pathogens in patients with proven histoplasmosis. Methods We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen testing for Histoplasma, Blastomyces, Aspergillus, Cryptococcus, and (1→3)-β-D-glucan were evaluated. Two different urine Histoplasma antigen assays were used during the study period. Results Fifty-seven of 182 (31.3%) patients reviewed had proven histoplasmosis and presented with acute pulmonary (n = 10), chronic pulmonary (n = 7), and disseminated (n = 40) disease. Forty-one (72%) of these patients were immunosuppressed. Urine Blastomyces antigen (93%) and serum (1→3)-β-D-glucan (88%) were commonly positive in patients with histoplasmosis, whereas Aspergillus antigen was detected in 50% of patients and Cryptococcus antigenemia was rare (5%). In patients with disseminated disease, the MiraVista urine Histoplasma antigen assay had higher sensitivity than the Viracor urine Histoplasma antigen assay (86% vs 50%, respectively; P = .019). Conclusions Noninvasive fungal antigen assays are helpful diagnostic tools; however, given their low specificity, clinicians must be aware of the various clinical presentations of invasive fungal infections and be aware of the limitations of these tests.

Reducing Repeat Blood Cultures in Febrile Neutropenia: A Single-Center Experience - Robinson, Evan D; Keng, Michael K; Thomas, Tanya D; Cox, Heather L; Park, Stacy C; Mathers, Amy J (Open Forum Infectious Diseases, 2022)
Abstract Background Limited data exist to guide blood culture ordering in persistent febrile neutropenia (FN), resulting in substantial variation in practice. Unnecessary repeat blood cultures have been associated with patient harm including increased antimicrobial exposure, hospital length of stay, catheter removal, and overall cost. Methods We conducted a single-center study of adult hematology-oncology patients with ≥3 days of FN. The yield of blood cultures was first evaluated in a 2-year historical cohort. Additionally, a pilot pre-/postintervention study was performed in non–stem cell transplant (SCT) patients following a change in our population clinical practice guideline from a recommendation of daily blood cultures to a clinically guided approach. The primary outcome was cultures collected per days of FN after day 3 of persistent FN. Results One hundred forty-six episodes of ≥3 days of FN in 108 patients were identified during the historical period. Day 1 blood cultures were positive in 23 of 146 (16%) episodes. Blood cultures were drawn on 374 of 513 (73%) subsequent episode-days (day 2–12) and were negative in 366 of 374 (98%). After the intervention, a 53% decrease was observed in the rate of total blood cultures collected (1.4 preintervention vs 0.7 postintervention; P = .03). Blood cultures obtained after 48 hours rarely yielded clinically significant organisms. Conclusions Repeat blood cultures are low-yield in persistent FN without new clinical change. A pilot intervention in non-SCT patients successfully reduced the frequency of blood culture collection.

Elevated cell-free DNA in respiratory viral infection and associated lung allograft dysfunction - Bazemore, Katrina; Permpalung, Nitipong; Mathew, Joby; Lemma, Merte; Haile, Betelihim; Avery, Robin; Kong, Hyesik; Jang, Moon Kyoo; Andargie, Temesgen; Gopinath, Shilpa; Nathan, Steven D.; Aryal, Shambhu; et al. (American Journal of Transplantation, 2022)
Keywords: %ddcfDNA; ACR; AMR; BAL; CLAD; DPT; FEV1; GRAfT; Genomic Research Alliance for Transplantation; HLA DSA; IVIG; LRTI; LTRs; NIH; NP; National Institutes of Health; PGD; RVI; SNPs; URTI; acute cellular rejection; antibody-mediated rejection; bronchiolitis obliterans (BOS); bronchoalveolar lavage; chronic lung allograft dysfunction; clinical research/practice; days post-transplant; donor-specific human leukocyte antigen antibodies; forced expiratory volume in 1 second; infection and infectious agents—viral; infectious disease; intravenous immune globulin; lower respiratory tract infection; lung (allograft) function/dysfunction; lung transplant recipients; lung transplantation/pulmonology; molecular biology: DNA; nasopharyngeal swab; percent donor-derived cell-free DNA; primary graft dysfunction; respiratory viral infection; single nucleotide polymorphisms; translational research/science; upper respiratory tract infection

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases - Chen, Tempe K; Batra, Jagmohan S; Michalik, David E; Casillas, Jacqueline; Patel, Ramesh; Ruiz, Maritza E; Hara, Harneet; Patel, Bhavita; Kadapakkam, Meena; Ch'Ng, James; Small, Catherine B; Zagaliotis, Panagiotis; et al. (Open Forum Infectious Diseases, 2022)
Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs).The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted.Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response).Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.

Outcomes of Nocardiosis and Treatment of Disseminated Infection in Solid Organ Transplant Recipients - Yetmar, Zachary A.; Challener, Douglas W.; Seville, Maria Teresa; Bosch, Wendelyn; Beam, Elena (Transplantation, 2022)

Elevated posaconazole trough concentrations are not associated with increased risk for posaconazole toxicity in lung transplant recipients - Sabatino, David C.; Lange, Nicholas W.; Salerno, David M.; Scheffert, Jenna (Clinical Transplantation, 2022)
Objective: Posaconazole is used for prophylaxis and treatment of invasive fungal infections in lung transplant recipients (LTR). Previous studies have not described the relationship between elevated posaconazole trough concentrations and adverse drug reactions in this population. Methods: This IRB-approved, retrospective cohort study at NewYork-Presbyterian Hospital included LTR who had posaconazole trough concentrations measured. The primary aim of this study was to evaluate elevated posaconazole trough concentrations and changes in liver function tests as well as QTc interval. A secondary aim of this study was to identify patient factors associated with elevated posaconazole trough levels. Results: A total of 109 LTR were included. The average age was 58.1 years (IQR, 48–65), the majority were male (56%). A total of 932 trough levels were assessed with a median number of 8 (IQR, 5–15) levels per patient. The median posaconazole trough concentration was 1.7 mg/L (IQR, 1.1–2.5). Hepatotoxicity, as defined by common terminology criteria for adverse events (CTCAE), was observed in 73.4% of subjects, with the majority classified as grade 1 (67.5%). However, there was no correlation between elevated posaconazole levels and aspartate aminotransferase (r = .03), alanine aminotransferase (r = .04), alkaline phosphatase (r = .04), and total bilirubin (r = .02). There was also no correlation between posaconazole trough concentrations and QTc interval (r = .03). Conclusion: This analysis demonstrates that no correlation exists between whole blood posaconazole levels and hepatotoxicity or QTc prolongation. Based on these results, posaconazole dose reductions may not be warranted for posaconazole levels that are significantly above the therapeutic target to avert risk for hepatotoxicity or QTc prolongation.

The impact of preservation fluid culture on graft site arteritis: a systematic review and metanalysis - Rinaldi, Matteo; Bonazzetti, Cecilia; Gatti, Milo; Caroccia, Natascia; Comai, Giorgia; Ravaioli, Matteo; Morelli, Maria Cristina; Viale, Pierluigi; Giannella, Maddalena (Transplant Infectious Disease, 2022)

Risk factors and outcome of concurrent and sequential multiviral cytomegalovirus, Epstein–Barr virus, BK virus, adenovirus and other viral reactivations in transplantation - Sim, Beatrice Z.; Yong, Kar Yee; Slavin, Monica A.; Yong, Michelle K. (Current Opinion in Infectious Diseases, 2022)

Coronavirus Disease 2019 (COVID-19): Frequently Asked Questions for Transplant Candidates, Recipients, and Care Givers - AST (2022)
Information regarding COVID-19 continues to change rapidly. This document will be updated with new information whenever possible. Please contact your transplant center with specific questions or concerns. Human coronaviruses are common viruses that cause the common cold, and do not usually cause serious symptoms. A novel coronavirus named SARS-CoV-2 causes the disease called Coronavirus disease 2019 (COVID-19). This coronavirus appeared in December 2019 and quickly spread all over the world. COVID-19 spreads from person to person through close contact, most often by respiratory droplets that are spread when an infected person coughs, sneezes or talks. People are thought to be most contagious when they have symptoms, but even those who are not experiencing symptoms or have mild symptoms can also spread the virus. Like many other viruses, mutations are common with SARS-CoV-2 and several important variants have been reported since December 2019. In late 2021, Omicron emerged and became the dominant variant around the world within a few weeks largely because its mutations allowed the virus to be even more infectious. Omicron has also shown an ability to escape immunity from vaccines or prior COVID-19 infections, causing a high number of breakthrough infections in both immunocompromised and non-immunocompromised individuals. New variants and subvariants of SARS-CoV-2 are expected to emerge.

Risk factors and outcomes of non-tuberculous mycobacteria infection in lung transplant recipients: A systematic review and meta-analysis - Marty, Paige K.; Yetmar, Zachary A.; Gerberi, Dana J.; Escalante, Patricio; Pennington, Kelly M.; Mahmood, Maryam (The Journal of Heart and Lung Transplantation, 2022)
Keywords: AFB; ATS/IDSA; Acid-fast bacilli; American Thoracic Society/Infectious Diseases Society of America; BOS; Bronchiolitis obliterans syndrome; CF; CI; CLAD; CMV; Chronic lung allograft dysfunction; Confidence interval; Cystic fibrosis; Cytomegalovirus; HR; Hazard ratio; ILD; Interstitial lung disease; LTR; Lung transplant recipient; MAC; Mycobacterium avium complex; NOS; NTM; Newcastle-Ottawa scale; Non-tuberculous mycobacteria; OLD; OR; Obstructive lung disease; Odds ratio; chronic lung allograft dysfunction; lung transplantation; mortality; mycobacterium abscessus; non-tuberculous mycobacteria

Pneumocystis jirovecii Pneumonia Prophylaxis with Intravenous Pentamidine in Adult Allogeneic Hematopoietic Stem Cell Transplant Patients - McCollam, Shiela; Lewis, James S.; Bubalo, Joseph; Diaz, Amber (Antimicrobial Agents and Chemotherapy, 2022)

Incidence of Invasive Fungal Infections in Patients With Previously Untreated Acute Myeloid Leukemia Receiving Venetoclax and Azacitidine - Zhang, Alexander; Johnson, Tanner; Abbott, Diana; Phupitakphol, Tanit; Gutman, Jonathan A; Pollyea, Daniel A; Koullias, Yiannis (Open Forum Infectious Diseases, 2022)
Abstract Background Acute myeloid leukemia (AML) is associated with poor prognosis, particularly in elderly patients with comorbidities. Combining azacitidine (AZA) with BCL-2 inhibitor venetoclax (VEN) demonstrated significant improvement in outcomes for newly-diagnosed AML patients compared to AZA alone. However, this regimen is myelosuppressive, and the incidence of invasive fungal infections (IFIs) and impact of antifungal prophylaxis are not well defined. Methods This retrospective cohort study evaluated newly-diagnosed AML patients treated with VEN/AZA at the University of Colorado Hospital from January 2014 to August 2020. Patients with history of prior IFI were excluded. Primary outcome was IFI incidence during VEN/AZA therapy. χ2 and Fisher exact tests assessed the impact of patient demographics, AML-specific risk factors, and receipt of antifungal prophylaxis on IFI incidence. Results 144 VEN/AZA-treated AML patients were included in the study. 25 (17%) patients developed IFI: 8% (n = 2) “proven,” 24% (n = 6) “probable,” and 68% (n = 17) “possible” per European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium criteria. There was no statistically significant association between IFI incidence with age, sex, or European LeukemiaNet classification. 10 patients received antifungal prophylaxis; none developed IFI. IFI incidence rate per 1000 patient-days was greatest 0–9 days after starting VEN/AZA, at 8.39. Conclusions Incidence of “proven” and “probable” IFI in our VEN/AZA-treated AML cohort was 5.6%, in-line with incidence rates reported by recent similar studies. Furthermore, IFI incidence decreased as days from starting VEN/AZA therapy increased.

Epidemiology of Lower Respiratory Tract Infections and Community-Acquired Respiratory Viruses in Patients with Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation: A Retrospective Cohort Study - Epstein, David J.; Liang, Emily C.; Sharifi, Husham; Lai, Yu Kuang; Arai, Sally; Graber-Naidich, Anna; Sundaram, Vandana; Nelson, Joanna; Hsu, Joe L. (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2022)
Keywords: Bronchiolitis obliterans syndrome; Graft-versus-host disease; Hematopoietic cell transplantation; Pulmonary infections

TID Recommendations for Organ Donation and Transplantation after COVID-19 - October 2022 - Pouch, Stephanie; Clemente, Wanessa Trindade; Tan, Ban Hock (2022)
The COVID-19 pandemic has had a significant impact on donor evaluation and organ procurement.1 As the virus entrenches itself, the risk of donor-derived infection must be balanced with the risk of morbidity and mortality while remaining on the transplant waitlist. Decisions to proceed with organ transplant locally must balance the existing capacity of the center, availability of testing for donors and candidates, and sufficient capacity to provide adequate occupational protection to recovery and transplant staff.2 The recommendations in this document are based upon current peer-reviewed literature and public health data and represent a consensus opinion from TID Council, all of whom are practicing clinicians. Given that knowledge about SARS-CoV-2 continues to evolve, the recommendations contained in this document are subject to change. Additionally, the authors recognize that access to diagnostic assays may vary globally, particularly in resource-limited settings, and local approaches to donor evaluation may need to be adopted accordingly.

Torque teno virus DNA load as a predictive marker of antibody response to a three-dose regimen of COVID-19 mRNA-based vaccine in lung transplant recipients - Gallais, Floriane; Renaud-Picard, Benjamin; Solis, Morgane; Laugel, Elodie; Soulier, Eric; Caillard, Sophie; Kessler, Romain; Fafi-Kremer, Samira (The Journal of Heart and Lung Transplantation, 2022)
BACKGROUND Previous studies have reported that lung transplant recipients (LTR) develop a poor response to two doses of COVID-19 vaccine, but data regarding the third dose are lacking. We investigated the antibody response after three doses of mRNA vaccine in LTR and its predictive factors. METHODS A total of 136 LTR, including 10 LTR previously infected and 126 COVID-19-naive LTR, were followed during and after three doses of mRNA vaccine. We retrospectively measured anti-receptor-binding domain (RBD) IgG response and neutralizing antibodies. In a posthoc analysis, we used a multivariate logistic regression model to assess the association between vaccine response and patient characteristics, including viral DNA load (VL) of the ubiquitous Torque teno virus (TTV) (optimal cut-off set by ROC curve analysis), which reflects the overall immunosuppression. RESULTS After 3 doses, 47/126 (37.3%) COVID-19-naive LTR had positive anti-RBD IgG (responders) and 14/126 (11.1%) had antibody titers above 264 Binding Antibody Units/mL. None neutralized the omicron variant versus 7 of the 10 previously infected LTR. Nonresponse was associated with TTV VL ≥6.2 log10 copies/mL before vaccination (Odds Ratio (OR) = 17.87, 95% confidence interval (CI95) = 3.02-105.72), mycophenolate treatment (OR = 4.73, CI95 = 1.46-15.34) and BNT162b2 (n = 34; vs mRNA-1273, n = 101) vaccine (OR = 6.72, CI95 = 1.75-25.92). In second dose non-responders, TTV VL ≥6.2 or <3.2 log10 copies/mL before the third dose was associated with low (0/19) and high (9/10) rates of seroconversion. CONCLUSION COVID-19-naive LTR respond poorly to three doses of mRNA vaccine, especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies.

Effect of influenza vaccination in solid organ transplant recipients: A nationwide population‐based cohort study - Harboe, Zitta Barrella; Modin, Daniel; Gustafsson, Finn; Perch, Michael; Gislason, Gunnar; Sørensen, Søren Schwartz; Rasmussen, Allan; Biering‐Sørensen, Tor; Nielsen, Susanne Dam (American Journal of Transplantation, 2022)
Vaccination can prevent influenza in solid organ transplant (SOT) recipients. Using a modified season‐specific approach over nine consecutive influenza seasons, we investigated influenza vaccination coverage and effectiveness in a population‐based nationwide cohort study that included all SOT recipients aged ≥18 years who were living in Denmark from December 1, 2007 to April 1, 2016. The primary outcome was the season‐specific risk of all‐cause pneumonia admission. Secondary outcomes were season‐specific influenza‐related admission, intensive care unit (ICU) admission, and all‐cause mortality. Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. In total, 11 381 person‐years of follow‐up data were collected from 5745 SOT recipients, 48% of whom were vaccinated. Influenza vaccination was associated with a reduced risk of all‐cause pneumonia admission (aHR, 0.83; 95% CI, 0.69–0.99; p = .035) and all‐cause mortality (aHR, 0.60; 95% CI, 0.47–0.76; p = .001), but not influenza‐related admission (aHR, 0.75; 95% CI, 0.46–1.22; p = .24) or ICU admission (aHR, 0.84; 95% CI, 0.67–1.06; p = .14) during the same season. Despite these benefits, uptake of influenza vaccination among SOT recipients was low. Therefore, annual influenza vaccination needs to be prioritized. , This nationwide cohort study over nine consecutive influenza seasons shows that seasonal influenza vaccination is associated with reduced risk of hospitalization for all‐cause pneumonia but that less than half of all solid organ transplant recipients were vaccinated.

Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients - Martini, Silvia; Tandoi, Francesco; Romagnoli, Renato; Rizzetto, Mario (Transplantation, 2022)
Hepatitis D is caused by the hepatitis D virus (HDV); it is the most severe form of viral hepatitis in humans, running an accelerated course to cirrhosis. There is no efficacious therapy, and liver transplantation provides the only therapeutic option for terminal HDV disease. However, HDV infection is prevalent in poor countries of the world with no access to liver transplant programs; liver grafting has been performed in high-income countries, where the prevalence of the infection has much diminished as a secondary effect of hepatitis B virus vaccination, and the demand for liver transplantation outlives in aging cirrhotics who acquired hepatitis D decades ago. This review describes the evolution of liver transplantation for HDV disease from its inception in 1987 to the present time, with an outlook to its future. It reports the progress in the prophylaxis of HDV reinfections to the success of the current standard of indefinite combination of hepatitis B virus antivirals with immunoglobulins against the hepatitis B surface antigen; however, the unique biology of the virus provides a rationale to reducing costs by limiting the administration of the immunoglobulins against the hepatitis B surface antigen. Export

Consensus Definitions of BK Polyomavirus Nephropathy in Renal Transplant Recipients for Clinical Trials - Imlay, Hannah; Baum, Paul; Brennan, Daniel C; Hanson, Kimberly E; Hodges, Michael R; Hodowanec, Aimee C; Komatsu, Takashi E; Ljungman, Per; Miller, Veronica; Natori, Yoichiro; Nickeleit, Volker; O’Rear, Jules; et al. (Clinical Infectious Diseases, 2022)
Background.  BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. Results and Discussion.  Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. Methods.  To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. Conclusions.  These definitions refine established principles of “proven” BKPyV disease and introduce a “probable” disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients.

An old confusion: entomophthoromycosis versus mucormycosis and their main differences - Acosta España, Jaime; Voigt, Kerstin (Frontiers in Microbiology, 2022)
Fungal diseases were underestimated for many years. And the global burden of fungal infections is substantial and has increased in recent years. Invasive fungal infections have been linked to several risk factors in humans which basically depend on the individual homeostasis of the patients. However, many fungi can infect even apparently healthy people. Knowledge of these pathogens is critical in reducing or stopping morbidity and/or mortality statistics due to fungal pathogens. Successful therapeutic strategies rely on rapid diagnosis of the causative fungal agent and the underlying disease. However, the terminology of the diseases was updated to existing phylogenetic classifications and led to confusion in the definition of mucormycosis, conidiobolomycosis, and basidiobolomycosis, which were previously grouped under the now-uncommon term zygomycosis. Therefore, the ecological, taxonomic, clinical, and diagnostic differences are addressed to optimize the understanding and definition of these diseases. The term ‘coenocytic hyphomycosis’ is proposed to summarize all fungal infections caused by Mucorales and species of Basidiobolus and Conidiobolus

Increasing Proportion of High-risk Cytomegalovirus Donor-Positive/Recipient-Negative Serostatus in Solid Organ Transplant Recipients - Imlay, Hannah; Wagener, Marilyn M.; Vutien, Philip; Perkins, James; Singh, Nina; Limaye, Ajit P. (Transplantation, 2022)
BACKGROUND: Cytomegalovirus (CMV) donor-positive/recipient-negative (D+R-) serostatus is independently associated with worse allograft and patient survival across solid organ transplant (SOT) types. We characterized trends in CMV D+R- serostatus among adult SOT recipients performed in the United States. METHODS: Donor (D) and recipient (R) CMV serostatus and demographic factors were obtained from the Scientific Registry of Transplant Recipients for persons ≥18 y undergoing a first SOT between January 1, 2000, and December 31, 2020. The proportions of D+R- SOTs over time were assessed using Chi square for trend and modeled through 2040. Factors associated with D/R seropositivity were assessed using logistic models. RESULTS: Among 472 549 SOTs, the average proportion of D+R- SOTs increased significantly among kidney, liver, heart, and lung between 2000 to 2009 and 2010 to 2020: 18.0% to 18.3% (P = 0.034), 19.4% to 21.8% (P < 0.001), 22.2% to 25.5% (P < 0.001), and 23.6% to 27.0% (P < 0.001), respectively. The increased proportion over time resulted from a disproportionate increase in R- (34.9% to 37.0% for all organ types, P < 0.001) and a smaller corresponding change in D+ (60.8% to 60.3%, P < 0.001). CONCLUSIONS: The proportion of high-risk CMV D+R- SOTs increased significantly across all organs and is projected to continue to increase. These findings inform population-level strategies to mitigate the negative impact of CMV D+R- in SOT.

Food Safety Home Page | CDC - CDC (2022)
Get information from CDC on preventing food poisoning, food poisoning symptoms, foodborne disease outbreaks, and recalled food.

COVID-19 Vaccination Schedule Infographic (Immunocompromised) - CDC (2022)

COVID-19 Vaccination Schedule Infographic (Not Immunocompromised) - CDC (2022)

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States - CDC (2022)

Five-Year Allograft Survival for Recipients of Kidney Transplants From Hepatitis C Virus Infected vs Uninfected Deceased Donors in the Direct-Acting Antiviral Therapy Era - Schaubel, Douglas E.; Tran, Amelia H.; Abt, Peter L.; Potluri, Vishnu S.; Goldberg, David S.; Reese, Peter P. (JAMA, 2022)
Many US deceased organ donors carry hepatitis C virus (HCV) infection, which can infect recipients during transplant. Historically, recipients of HCV-infected organ transplants only had access to ineffective interferon-based antiviral regimens and have experienced elevated rates of allograft failure and death. Most HCV-infected donor organs were discarded. However, starting in 2016, the availability of direct-acting antiviral therapy enabled transplant trials of HCV-infected kidneys into HCV-uninfected recipients, with most trials reporting 100% HCV cure rates and excellent short-term allograft function.

Hygiene Practices Around Animals - CDC (Centers for Disease Control and Prevention, 2022)
Get information about hygiene practice around animals. Learn how to stay safe and healthy when around animals by washing your hands.

La tos y los estornudos (2022)
Cubrirse al toser y estornudar ayuda a prevenir la propagación de enfermedades respiratorias graves.

Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial - Avery, Robin K; Alain, Sophie; Alexander, Barbara D; Blumberg, Emily A; Chemaly, Roy F; Cordonnier, Catherine; Duarte, Rafael F; Florescu, Diana F; Kamar, Nassim; Kumar, Deepali; Maertens, Johan; Marty, Francisco M; et al. (Clinical Infectious Diseases, 2022)
Background.  Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. Methods.  In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. Results.  352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80–42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02–16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs. Conclusions.  Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT.

Controversies in the Management of Central Nervous System Coccidioidomycosis - Thompson, George R; Ampel, Neil M; Blair, Janis E; Donovan, Fariba; Fierer, Joshua; Galgiani, John N; Heidari, Arash; Johnson, Royce; Shatsky, Stanley A; Uchiyama, Christopher M; Stevens, David A (Clinical Infectious Diseases, 2022)
Abstract Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

Paracoccidioidomycosis: Current Status and Future Trends - Hahn, Rosane Christine; Hagen, Ferry; Mendes, Rinaldo Poncio; Burger, Eva; Nery, Andreia Ferreira; Siqueira, Nathan Pereira; Guevara, Armando; Rodrigues, Anderson Messias; de Camargo, Zoilo Pires (Clinical Microbiology Reviews, 2022)
Paracoccidioidomycosis (PCM), initially reported in 1908 in the city of São Paulo, Brazil, by Adolpho Lutz, is primarily a systemic and neglected tropical mycosis that may affect individuals with certain risk factors around Latin America, especially Brazil. Paracoccidioides brasiliensis sensu stricto , a classical thermodimorphic fungus associated with PCM, was long considered to represent a monotypic taxon. However, advances in molecular taxonomy revealed several cryptic species, including Paracoccidioides americana , P. restrepiensis , P. venezuelensis , and P. lutzii , that show a preference for skin and mucous membranes, lymph nodes, and respiratory organs but can also affect many other organs. , SUMMARY Paracoccidioidomycosis (PCM), initially reported in 1908 in the city of São Paulo, Brazil, by Adolpho Lutz, is primarily a systemic and neglected tropical mycosis that may affect individuals with certain risk factors around Latin America, especially Brazil. Paracoccidioides brasiliensis sensu stricto , a classical thermodimorphic fungus associated with PCM, was long considered to represent a monotypic taxon. However, advances in molecular taxonomy revealed several cryptic species, including Paracoccidioides americana , P. restrepiensis , P. venezuelensis , and P. lutzii , that show a preference for skin and mucous membranes, lymph nodes, and respiratory organs but can also affect many other organs. The classical diagnosis of PCM benefits from direct microscopy culture-based, biochemical, and immunological assays in a general microbiology laboratory practice providing a generic identification of the agents. However, molecular assays should be employed to identify Paracoccidioides isolates to the species level, data that would be complemented by epidemiological investigations. From a clinical perspective, all probable and confirmed cases should be treated. The choice of treatment and its duration must be considered, along with the affected organs, process severity, history of previous treatment failure, possibility of administering oral medication, associated diseases, pregnancy, and patient compliance with the proposed treatment regimen. Nevertheless, even after appropriate treatment, there may be relapses, which generally occur 5 years after the apparent cure following treatment, and also, the mycosis may be confused with other diseases. This review provides a comprehensive and critical overview of the immunopathology, laboratory diagnosis, clinical aspects, and current treatment of PCM, highlighting current issues in the identification, treatment, and patient follow-up in light of recent Paracoccidioides species taxonomic developments.

COVID-19 Vaccine Interim COVID-19 Immunization Schedule for Persons 6 Months of Age and Older (Tables) - CDC (2022)

Monkeypox in Transplantation - TID Guidance September 2022 - Clemente, Wanessa Trindade; Watcharananan, Siriorn P.; Tan, Ban Hock (2022)
This document provides guidance for transplant practitioners on monkeypox (MPX) and organ transplants. We acknowledge that our current understanding of the disease is incomplete. This guidance will require revision as new evidence emerges. In these guidelines, we adopt a conservative approach to organ donation with regards to MPX transmission. We err on the side of safety. We recognize that many institutions already have experience with MPX. This document makes suggestions, but its aim is not to be dogmatic. Individual programs and patients should make their own decisions based on the clinical circumstances of the potential donor and the needs of the potential recipient, as well as their own experience with MPX disease.

Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial - Millon, Laurence; Caillot, Denis; Berceanu, Ana; Bretagne, Stéphane; Lanternier, Fanny; Morio, Florent; Letscher-Bru, Valérie; Dalle, Frédéric; Denis, Blandine; Alanio, Alexandre; Boutoille, David; Bougnoux, Marie Elisabeth; et al. (Clinical Infectious Diseases, 2022)
Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the early diagnosis and follow-up of mucormycosis.We prospectively enrolled 232 patients with suspicion of invasive mold disease, evaluated using standard imaging and mycological procedures. Thirteen additional patients with proven or probable mucormycosis were included to analyze DNA load kinetics. Serum samples were collected twice-a-week for Mucorales qPCR tests targeting the Mucorales genera Lichtheimia, Rhizomucor, and Mucor/Rhizopus.The sensitivity was 85.2%, specificity 89.8%, and positive and negative likelihood ratios 8.3 and 0.17, respectively in this prospective study. The first Mucorales qPCR-positive serum was observed a median of 4 days (interquartile range [IQR], 0–9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, −2 to 6) before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate (adjusted hazard ratio = 0·15, 95% confidence interval [.03–.73], P = .02).Our study argues for the inclusion of qPCR for the detection of circulating Mucorales DNA for mucormycosis diagnosis and follow-up after treatment initiation. Positive results should be added to the criteria for the consensual definitions from the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), as already done for Aspergillus PCR.

Impact of Discontinuing Levofloxacin Prophylaxis on Bloodstream Infections in Neutropenic Hematopoietic Stem Cell Transplantation Patients - Guimarães, Thaís; Borges, Igor Carmo; Spadão, Fernanda de Souza; Mariano, Livia; Nascimento, Marina de Mattos; Higashino, Hermes; Rossi, Flavia; Rocha, Vanderson; Costa, Silvia Figueiredo (Antibiotics, 2022)
Multidrug-resistant pathogens have emerged worldwide. We have driven the hypothesis that the non-use of fluoroquinolone prophylaxis during neutropenia could reduce antibiotic resistance in Gram-negative bacteria that cause bloodstream infections (BSIs) in hematopoietic stem cell transplantation (HSCT) patients and that this change in resistance pattern could lead to an impact on BSI mortality. This is a quasi-experimental study comparing BSI incidence, resistance patterns of bacteria that cause BSI, and BSI mortality when levofloxacin prophylaxis was routine for neutropenic HSCT patients (2016–2018) to when fluoroquinolone prophylaxis was discontinued in our center (2019). Bivariate comparisons and multivariate logistic regression models were used for analyses. A total of 310 HSCTs (66 (21%) allogeneic and 244 (79%) autologous) were performed during the study period. Sixty (19%) patients had BSIs, 30 in each evaluated period. The discontinuation of levofloxacin prophylaxis was associated with an increase in BSI incidence and a decrease in the resistance rates of causative BSI bacteria and in BSI 30-day mortality. The increase in the rate of resistant bacteria causing BSI and in BSI mortality might outweigh the benefits of a decrease in BSI incidence caused by fluoroquinolone prophylaxis in neutropenic HSCT patients. We suggest that the routine use of fluoroquinolone in this context be revisited.
Keywords: bacterial resistance; bloodstream infection; fluoroquinolone; hematopoietic stem cell transplantation; neutropenia

Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation - Swarte, J. Casper; Li, Yanni; Hu, Shixian; Björk, Johannes R.; Gacesa, Ranko; Vich Vila, Arnau; Douwes, Rianne M.; Collij, Valerie; Kurilshikov, Alexander; Post, Adrian; Klaassen, Marjolein A. Y.; Eisenga, Michele F.; et al. (Science Translational Medicine, 2022)
Organ transplantation is a life-saving treatment for patients with end-stage disease, but survival rates after transplantation vary considerably. There is now increasing evidence that the gut microbiome is linked to the survival of patients undergoing hematopoietic cell transplant, yet little is known about the role of the gut microbiome in solid organ transplantation. We analyzed 1370 fecal samples from 415 liver and 672 renal transplant recipients using shotgun metagenomic sequencing to assess microbial taxonomy, metabolic pathways, antibiotic resistance genes, and virulence factors. To quantify taxonomic and metabolic dysbiosis, we also analyzed 1183 age-, sex-, and body mass index–matched controls from the same population. In addition, a subset of 78 renal transplant recipients was followed longitudinally from pretransplantation to 24 months after transplantation. Our data showed that both liver and kidney transplant recipients suffered from gut dysbiosis, including lower microbial diversity, increased abundance of unhealthy microbial species, decreased abundance of important metabolic pathways, and increased prevalence and diversity of antibiotic resistance genes and virulence factors. These changes were found to persist up to 20 years after transplantation. Last, we demonstrated that the use of immunosuppressive drugs was associated with the observed dysbiosis and that the extent of dysbiosis was associated with increased mortality after transplantation. This study represents a step toward potential microbiome-targeted interventions that might influence the outcomes of recipients of solid organ transplantation. , Dysbiosis of the gut microbiome after solid organ transplantation is induced by immunosuppression and antibiotics and linked to increased mortality. , Damaging dysbiosis Reduced gut microbial diversity after allogeneic stem cell transplantation has been associated with decreased survival, but the role of the gut microbiome after solid organ transplantation is not as well studied. Here, Swarte and colleagues studied dysbiosis of the gut microbiome in a large cohort of individuals with end-stage liver or kidney disease before and after organ transplantation. Transplant recipients suffered from gut dysbiosis, with lower diversity and increased abundance of unhealthy species, virulence factors, and antibiotic resistance genes. Furthermore, immunosuppressive drug use was associated with dysbiosis, and increased dysbiosis was associated with increased mortality after transplantation. These results suggest that microbiome-targeted interventions could potentially affect outcomes after solid organ transplantation.

Hepatitis E Virus Infection in Cancer Patients - Chiu, Chia-Yu; Zhang, Hao Chi; Westin, Jason; Hosing, Chitra; Torres, Harrys A. (Transplantation and Cellular Therapy, 2022)
Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection and failed ribavirin treatment. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment.
Keywords: Chimeric Antigen Receptor (CAR) T-Cell Therapy; Stem Cell Transplantation; hematologic malignancies; hepatitis E; ribavirin

Incidence of invasive fungal infections in patients with hematological malignancies receiving ibrutinib therapy in south-east Austria - Egger, Matthias; Gornicec, Max; Wölfler, Albert; Lembeck, Anna Lena; Tinchon, Christoph; Maderdonner, Manuela; Prattes, Juergen (Medical Mycology, 2022)
Since the broad implementation of ibrutinib therapy, an increasing number of studies have been reporting on invasive fungal infections (IFI) associated with ibrutinib administration. We conducted a retrospective cohort study in three hospitals in south-east Austria in order to assess the local epidemiology of ibrutinib associated IFIs. One-hundred-thirteen patients with underlying hematological malignancy were included in the study. During the study period, a single IFI episode was observed, which corresponds to an IFI incidence of 2.3 cases per 100 person years (95% CI: 0.12–11.47). IFIs during ibrutinib therapy seem to be a rare event in case of absent additional risk factors for IFIs.Ibrutinib is an effective drug to treat a variety of blood cancers, but it might increase risk for life-threatening invasive fungal infections (IFIs). In our study, a low number (1 IFI per 43 patient years) of patients on ibrutinib developed an IFI.

Infection, Rejection, and the Connection - Higdon, Lauren E.; Tan, Jane C.; Maltzman, Jonathan S. (Transplantation, 2022)
Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that resembles the clinical pathology of rejection, and this complicates accurate diagnosis. Moreover, T cells specific for viral infection can lead to rejection through heterologous immunity to donor antigen directly mediated by antiviral cells. Thus, viral infections and allograft rejection interact in multiple ways that are important to maintain immunologic homeostasis in solid organ transplant recipients. Better insight into this dynamic interplay will help promote long-term transplant survival. (Transplantation 2022;00: 00–00).

Nocardia Infections in Hematopoietic Cell Transplant Recipients: A Multicenter International Retrospective Study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation - Averbuch, Diana; De Greef, Julien; Duréault, Amelie; Wendel, Lotus; Tridello, Gloria; Lebeaux, David; Mikulska, Malgorzata; Gil, Lidia; Knelange, Nina; Zuckerman, Tsila; Roussel, Xavier; Robin, Christine; et al. (Clinical Infectious Diseases, 2022)
Abstract Background Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population. Methods This retrospective international study reviewed nocardiosis episodes in HCT recipients (1/1/2000–31/12/2018; 135 transplant centers; 33 countries) and described their clinical, microbiological, radiological, and outcome characteristics. Results We identified 81 nocardiosis episodes in 74 allo- and 7 auto-HCT recipients. Nocardiosis occurred a median of 8 (IQR: 4–18) months post-HCT. The most frequently involved organs were lungs (70/81; 86%) and brain (30/81; 37%); 29 (36%) patients were afebrile; 46/81 (57%) had disseminated infections. The most common lung imaging findings were consolidations (33/68; 49%) or nodules (32/68; 47%); brain imaging findings were multiple brain abscesses (19/30; 63%). Ten of 30 (33%) patients with brain involvement lacked neurological symptoms. Fourteen of 48 (29%) patients were bacteremic. Nocardia farcinica was the most common among molecularly identified species (27%; 12/44). Highest susceptibility rates were reported to linezolid (45/45; 100%), amikacin (56/57; 98%), trimethoprim-sulfamethoxazole (57/63; 90%), and imipenem (49/57; 86%). One-year and last follow-up (IQR: 4–42.5 months) all-cause mortality were 40% (32/81) and 52% (42/81), respectively. In the multivariable analysis, underlying disease not in complete remission (HR: 2.81; 95% CI: 1.32–5.95) and prior bacterial infection (HR: 3.42; 95% CI: 1.62–7.22) were associated with higher 1-year all-cause mortality. Conclusions Nocardiosis is a late post-HCT infection usually manifesting as a pulmonary disease with frequent dissemination, brain infection, and bacteremia. Brain imaging should be performed in HCT recipients with nocardiosis regardless of neurological symptoms. Overall mortality is high.

Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS) - Haidar, Ghady; Agha, Mounzer; Bilderback, Andrew; Lukanski, Amy; Linstrum, Kelsey; Troyan, Rachel; Rothenberger, Scott; McMahon, Deborah K; Crandall, Melissa D; Sobolewksi, Michele D; Nathan Enick, P; Jacobs, Jana L; et al. (Clinical Infectious Diseases, 2022)
Background.   We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. Methods.   Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. Results.   A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. Conclusions.   Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma - Little, Jessica S.; Aleissa, Muneerah M.; Beluch, Katherine; Gonzalez-Bocco, Isabel H.; Marty, Francisco M.; Manne-Goehler, Jennifer; Koo, Sophia; Hammond, Sarah P.; Jacobson, Caron A. (Blood Advances, 2022)
CAR T-cell therapy has revolutionized the treatment of hematologic malignancies, although its use may be complicated by toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported after CAR T-cell therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal prophylaxis strategies are widely debated. We performed a single-center retrospective study of 280 adults receiving CD19 CAR T-cell therapy for non-Hodgkin lymphoma (NHL) from December 2017 through September 2021. Patients did not receive routine antiyeast or antimold prophylaxis. IFD was identified between day of cell infusion and last follow-up. Cumulative incidence functions were calculated at 100 days and 18 months based on time to IFD, using dates of IFD-free death, initiation of salvage treatment, and hematopoietic cell transplantation as competing risks. Eight patients (2.9%) developed IFD, including 3 Pneumocystis jirovecii pneumonia, 3 invasive mold infections (IMIs), and 2 invasive yeast infections (IYIs). The 100-day cumulative incidence of IFD accounting for competing risks was 1.8% (95% confidence interval [CI], 0.8% to 4.4%). Among the 280 patients, early toxicities including CRS (85%) and ICANS (55%) and late toxicities after day 30 including grades 3 and 4 neutropenia (41%) and low CD4 T-cell count (20%) were common. IFD was rare among patients who received CD19 CAR T-cell therapy for NHL in the absence of routine antifungal prophylaxis, despite frequent toxicities. These results suggest that, in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated.

Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection - Santos Bravo, Marta; Plault, Nicolas; Sánchez-Palomino, Sonsoles; Rodríguez, Cristina; Navarro Gabriel, Mireia; Mosquera, María Mar; Fernández Avilés, Francesc; Suarez-Lledó, María; Rovira, Montserrat; Bodro, Marta; Moreno, Asunción; Linares, Laura; et al. (The Journal of Infectious Diseases, 2022)
This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients.Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping.Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Surveillance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis - United States, 2019 - Smith, Dallas J.; Williams, Samantha L.; Endemic Mycoses State Partners Group; Benedict, Kaitlin M.; Jackson, Brendan R.; Toda, Mitsuru (Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C.: 2002), 2022)
PROBLEM/CONDITION: Coccidioidomycosis, histoplasmosis, and blastomycosis are underdiagnosed fungal diseases that often mimic bacterial or viral pneumonia and can cause disseminated disease and death. These diseases are caused by inhalation of fungal spores that have distinct geographic niches in the environment (e.g., soil or dust), and distribution is highly susceptible to climate changes such as expanding arid regions for coccidioidomycosis, the northward expansion of histoplasmosis, and areas like New York reporting cases of blastomycosis previously thought to be nonendemic. The national incidence of coccidioidomycosis, histoplasmosis, and blastomycosis is poorly characterized. REPORTING PERIOD: 2019. DESCRIPTION OF SYSTEM: The National Notifiable Diseases Surveillance System (NNDSS) tracks cases of coccidioidomycosis, a nationally notifiable condition reported to CDC by 26 states and the District of Columbia. Neither histoplasmosis nor blastomycosis is a nationally notifiable condition; however, histoplasmosis is voluntarily reported in 13 states and blastomycosis in five states. Health departments classify cases based on the definitions established by the Council of State and Territorial Epidemiologists. RESULTS: In 2019, a total of 20,061 confirmed coccidioidomycosis, 1,124 confirmed and probable histoplasmosis, and 240 confirmed and probable blastomycosis cases were reported to CDC. Arizona and California reported 97% of coccidioidomycosis cases, and Minnesota and Wisconsin reported 75% of blastomycosis cases. Illinois reported the greatest percentage (26%) of histoplasmosis cases. All three diseases were more common among males, and the proportion for blastomycosis (70%) was substantially higher than for histoplasmosis (56%) or coccidioidomycosis (52%). Coccidioidomycosis incidence was approximately four times higher for non-Hispanic American Indian or Alaska Native (AI/AN) persons (17.3 per 100,000 population) and almost three times higher for Hispanic or Latino persons (11.2) compared with non-Hispanic White (White) persons (4.1). Histoplasmosis incidence was similar across racial and ethnic categories (range: 0.9-1.3). Blastomycosis incidence was approximately six times as high among AI/AN persons (4.5) and approximately twice as high among non-Hispanic Asian and Native Hawaiian or other Pacific Islander persons (1.6) compared with White persons (0.7). More than one half of histoplasmosis (54%) and blastomycosis (65%) patients were hospitalized, and 5% of histoplasmosis and 9% of blastomycosis patients died. States in which coccidioidomycosis is not known to be endemic had more cases in spring (March, April, and May) than during other seasons, whereas the number of cases peaked slightly in autumn (September, October, and November) for histoplasmosis and in winter (December, January, and February) for blastomycosis. INTERPRETATION: Coccidioidomycosis, histoplasmosis, and blastomycosis are diseases occurring in geographical niches within the United States. These diseases cause substantial illness, with approximately 20,000 coccidioidomycosis cases reported in 2019. Although substantially fewer histoplasmosis and blastomycosis cases were reported, surveillance was much more limited and underdiagnosis was likely, as evidenced by high hospitalization and death rates. This suggests that persons with milder symptoms might not seek medical evaluation and the symptoms self-resolve or the illnesses are misdiagnosed as other, more common respiratory diseases. PUBLIC HEALTH ACTION: Improved surveillance is necessary to better characterize coccidioidomycosis severity and to improve detection of histoplasmosis and blastomycosis. These findings might guide improvements in testing practices that enable timely diagnosis and treatment of fungal diseases. Clinicians and health care professionals should consider coccidioidomycosis, histoplasmosis, and blastomycosis in patients with community-acquired pneumonia or other acute infections of the lower respiratory tract who live in or have traveled to areas where the causative fungi are known to be present in the environment. Culturally appropriate tailored educational messages might help improve diagnosis and treatment. Public health response to these three diseases is hindered because information gathered from states' routine surveillance does not include data on populations at risk and sources of exposure. Broader surveillance that includes expansion to other states, and more detail about potential exposures and relevant host factors can describe epidemiologic trends, populations at risk, and disease prevention strategies.
Keywords: Blastomycosis; Coccidioidomycosis; Histoplasmosis; Humans; Incidence; Male; Population Surveillance; Travel; United States

Shorter antibiotic courses in the immunocompromised: the impossible dream? - Imlay, Hannah; Laundy, Nicholas C.; Forrest, Graeme N.; Slavin, Monica A. (Clinical Microbiology and Infection, 2022)
Keywords: Antimicrobial stewardship; Febrile neutropenia; Infection short-course therapy; Solid organ transplantation; Stem cell transplantation

Drug Resistance Mutations and Associated Phenotypes Detected in Clinical Trials of Maribavir for Treatment of Cytomegalovirus Infection - Chou, Sunwen; Song, Kening; Wu, Jingyang; Bo, Tien; Crumpacker, Clyde (The Journal of Infectious Diseases, 2022)
In separate phase 2 trials, 120 patients received maribavir for cytomegalovirus (CMV) infection failing conventional therapy (trial 202) and 119 received maribavir for asymptomatic infection (trial 203). Overall, 172 cleared their CMV infection (CMV DNA <200 copies/mL) within 6 weeks.Baseline and posttreatment plasma samples were tested for mutations in viral genes UL97, UL54, and/or UL27. Selected viral mutants were phenotyped for drug susceptibility.Baseline samples revealed UL54 mutations newly phenotyped as conferring resistance to standard DNA polymerase inhibitor(s), including K493N, P497S, K513T, L565V, V823A, A987V, and E989D. Of 29 patients (including 25 from trial 202) who cleared but later experienced recurrent CMV infection while on maribavir, 23 had available UL97 genotyping data; 17 had known resistance mutations (T409M or H411Y) and 5 additional had UL97 C480F alone. The newly phenotyped mutation C480F conferred high-grade maribavir resistance and low-grade ganciclovir resistance. Among 25 who did not respond to >14 days of therapy, 9 showed T409M or H411Y and 4 others showed C480F alone.After maribavir therapy (400–1200 mg twice daily), UL97 mutations T409M, H411Y, or C480F emerge to confer maribavir resistance in patients with recurrent CMV infection while on therapy or no response to therapy.NCT01611974 and EudraCT 2010-024247-32.

New Perspectives on Antimicrobial Agents: Isavuconazole - Lewis, James S.; Wiederhold, Nathan P.; Hakki, Morgan; Thompson, George R. (Antimicrobial Agents and Chemotherapy, 2022)

New approaches to management of fever and neutropenia in high-risk patients - Douglas, Abby; Thursky, Karin; Slavin, Monica (Current Opinion in Infectious Diseases, 2022)
Acute leukaemic and autologous HCT patients with resolved neutropenic fever prior to count recovery can have empiric therapy safely discontinued or de-escalated. There is an emerging role of FDG-PET/CT to support decision-making about antibiotic and antifungal use in high-risk persistent/recurrent neutropenic fever patients.

Revisiting the Evidence Base for Modern Day Practice of the Treatment of Toxoplasmic Encephalitis: A Systematic Review and Meta-Analysis - Prosty, Connor; Hanula, Ryan; Levin, Yossef; Bogoch, Isaac I; McDonald, Emily G; Lee, Todd C (Clinical Infectious Diseases, 2022)
Toxoplasmic encephalitis (TE) is an opportunistic infection of people living with HIV or other causes of immunosuppression. For decades, the standard of care has been combination therapy with pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C). However, a substantial price increase has starkly limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to systematically review the evidence to compare the efficacy and safety of pyrimethamine-containing therapies versus TMP-SMX.We searched for and included randomized controlled trials (RCT) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients experiencing clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies.We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Pooled proportions of clinical and radiologic response or mortality or were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P > 0.05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%, 95%CI 4.7-11.4, I2 = 0.0%) versus P-S (30.5%, 95%CI 27.1-34.2, I2 = 0.0%, P < 0.01) or P-C (13.7%, 95%CI 9.8-18.8, I2 = 32.0%, P = 0.031). These results were consistent in analyses restricted to RCT data.Identified studies only included persons living with HIV and most predated modern antiretroviral treatment.TMP-SMX appears to be as effective and safer than the pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to P-S or P-C and a revisiting of the guidelines.

Monkeypox FAQs for Transplant Community (American Society of Transplantation, 2022)
This resource was created on August 4, 2022. View the PDF version

Monkeypox FAQ - Razonable, Raymund; Chin-Hong, Peter; Humar, Atul; Ison, Michael; Michaels, Marian; Subramanian, Aruna; Kumar, Deepali (2022)

Current Role of Prospective Monitoring, Pre-emptive and Prophylactic Therapy for Human Herpesvirus-6 after Allogeneic Stem Cell Transplantation - Handley, Guy (Open Forum Infectious Diseases, 2022)
Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic stem cell transplantation (SCT). Most patients are asymptomatic and viremia often resolves without therapy; however, transplant related complications may be associated with reactivation. Multiple presentations have been attributed to HHV-6 reactivation after SCT including encephalitis. Several strategies have been trialed to reduce such risks or complications. Challenges exist with prospective monitoring strategies, and established thresholds of high-level reactivation may be limited. Three published guidelines and extensive trials focusing on pre-emptive and prophylactic strategies are reviewed. Future areas of investigation and high-risk populations are described. Existing trials and testing platforms have significant limitations, and to date no clear benefit for a pre-emptive or prophylactic intervention has been demonstrated.

New Perspectives on Antimicrobial Agents: Maribavir - Halpern-Cohen, Virginie; Blumberg, Emily A. (Antimicrobial Agents and Chemotherapy, 2022)
Maribavir was approved by the U.S. Food and Drug Administration in November 2021 for the treatment of adult and pediatric patients with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet. Maribavir is an oral benzimidazole riboside with potent and selective multimodal anti-CMV activity. It utilizes a novel mechanism of action which confers activity against CMV strains that are resistant to traditional anti-CMV agents, and also offers a more favorable safety proﬁle relative to the dose-limiting side effects of previously available therapies. Maribavir was initially studied as an agent for CMV prophylaxis in solid organ and hematopoietic stem cell recipients, but initial phase III trials failed to meet clinical efﬁcacy endpoints. It has been more recently studied as a therapeutic agent at higher doses for refractoryresistant (R-R) CMV infections with favorable outcomes. After an overview of maribavir’s chemistry and clinical pharmacology, this review will summarize clinical efﬁcacy, safety, tolerability, and resistance data associated with maribavir therapy.

The Relationship Between Antibiotic Agent and Mortality in Patients With Febrile Neutropenia due to Staphylococcal Bloodstream Infection: A Multicenter Cohort Study - Aleissa, Muneerah M; Gonzalez-Bocco, Isabel H; Zekery-Saad, Sara; Kubiak, David W; Zhang, Eric M; Signorelli, Jessie; Hammond, Sarah P; Mohareb, Amir M; Luskin, Marlise R; Manne-Goehler, Jennifer; Marty, Francisco M (Open Forum Infectious Diseases, 2022)
Methicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of bloodstream infection (BSI) in patients with febrile neutropenia, but treatment practices vary, and guidelines are not clear on the optimal regimen.We conducted a multicenter retrospective cohort study of MSSA BSI in febrile neutropenia. We divided patients into 3 treatment groups: (1) broad-spectrum beta-lactams (ie, piperacillin-tazobactam, cefepime, meropenem); (2) narrow-spectrum beta-lactams (ie, cefazolin, oxacillin, nafcillin); and (3) combination beta-lactams (ie, both narrow- and broad-spectrum). We used multivariable logistic regression to compare 60-day mortality and bacteremia recurrence while adjusting for potential confounders.We identified 889 patients with MSSA BSI, 128 of whom had neutropenia at the time of the index culture: median age 56 (interquartile range, 43–65) years and 76 (59%) male. Of those, 56 (44%) received broad-spectrum beta-lactams, 30 (23%) received narrow-spectrum beta-lactams, and 42 (33%) received combination therapy. After adjusting for covariates, including disease severity, combination therapy was associated with a significantly higher odds for 60-day all-cause mortality compared with broad spectrum beta-lactams (adjusted odds ratio [aOR], 3.39; 95% confidence interval [CI], 1.29–8.89; P = .013) and compared with narrow spectrum beta-lactams, although the latter was not statistically significant (aOR, 3.30; 95% CI, .80–13.61; P = .071).Use of combination beta-lactam therapy in patients with MSSA BSI and febrile neutropenia is associated with a higher mortality compared with treatment with broad-spectrum beta-lactam after adjusting for potential confounders. Patients in this study who transitioned to narrow-spectrum beta-lactam antibiotics did not have worse clinical outcomes compared with those who continued broad-spectrum beta-lactam therapy.

[18F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial - Douglas, Abby; Thursky, Karin; Spelman, Timothy; Szer, Jeff; Bajel, Ashish; Harrison, Simon; Tio, Shio Yen; Bupha-Intr, Olivia; Tew, Michelle; Worth, Leon; Teh, Benjamin; Chee, Lynette; et al. (The Lancet Haematology, 2022)

Pathogen Detection by Metagenomic Next-Generation Sequencing During Neutropenic Fever in Patients With Hematological Malignancies - Schulz, Eduard; Grumaz, Silke; Hatzl, Stefan; Gornicec, Maximilian; Valentin, Thomas; Huber-Kraßnitzer, Bianca; Kriegl, Lisa; Uhl, Barbara; Deutsch, Alexander; Greinix, Hildegard; Krause, Robert; Neumeister, Peter (Open Forum Infectious Diseases, 2022)
Febrile neutropenia (FN) after chemotherapy is a major cause of morbidity during cancer treatment. The performance of metagenomic next-generation sequencing (mNGS) of circulating cell-free deoxyribonucleic acid from plasma may be superior to blood culture (BC) diagnostics for identification of causative pathogens. The aim of this study was to validate mNGS (DISQVER test) for the detection of pathogens in hematologic patients with FN.We collected paired whole blood specimens from central venous catheter and peripheral vein during FN for BC and mNGS testing. We repeated paired sampling at the earliest after 3 days of fever, which was defined as 1 FN episode. All clinical data were retrospectively reviewed by an infectious disease expert panel. We calculated percent positive agreement (PPA), percent negative agreement (PNA), percent overall agreement (POA), and sensitivity and specificity.We analyzed a total of 98 unselected FN episodes in 61 patients who developed predominantly FN after conditioning therapy for allogeneic (n = 22) or autologous (n = 21) hematopoietic stem cell transplantation. Success rate of mNGS was 99% (97 of 98). Positivity rate of mNGS was 43% (42 of 97) overall and 32% (31 of 97) excluding viruses compared to 14% (14 of 98) in BC. The PPA, PNA, and POA between mNGS and BC were 84.6% (95% confidence interval [CI], 54.6% to 98.1%), 63.1% (95% CI, 51.9% to 73.4%), and 66% (95% CI, 55.7% to 75.3%), respectively. Sensitivity for bacteria or fungi was 40% (95% CI, 28.0% to 52.9%) and 18.5% (95% CI, 9.9% to 30.0%), respectively.Pathogen detection by mNGS (DISQVER) during unselected FN episodes shows 2-fold higher sensitivity and a broader pathogen spectrum than BC.

Donors with human immunodeficiency virus and hepatitis C virus for solid organ transplantation: what's new - Lushniak, Stephanie A.; Durand, Christine M. (Current Opinion in Infectious Diseases, 2022)
Purpose of the review Passage of the HOPE Act and the advent of direct-acting antiviral (DAA) therapies have allowed for expansion of the donor organ pool to include donors with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), thus providing new opportunities for waitlist candidates. This article provides updates on recent studies in solid organ transplantation (SOT) utilizing donors with HIV and HCV. Recent findings The first pilot studies of kidney and liver transplantation from donors-with-HIV to recipients-with-HIV (HIV D+/R+) show robust patient survival, comparable graft survival to transplantation from donors without HIV (HIV D-/R+) and no increased rates of HIV breakthrough. The number of HIV D+ organs utilized has been lower than initial estimates due to several potential factors. With high numbers of overdose deaths from the opioid epidemic, there have been more HCV D+ organs available, leading to transplantation in recipients without HCV (HCV D+/R-) in combination with DAAs. Outcomes in both abdominal and thoracic HCV D+/R transplantation are excellent. Summary With recent findings of good outcomes in both HIV D+/R+ and HCV D+/R- SOT, we feel the evidence supports both practices as standard clinical care options to mitigate organ shortage and reduce waitlist mortality.

Antivirals with Activity Against Monkeypox: A Clinically Oriented Review - Siegrist, Emily A; Sassine, Joseph (Clinical Infectious Diseases, 2022)
Monkeypox virus is an emergent human pathogen. While it is less lethal than smallpox, it can still cause significant morbidity and mortality. In this review, we explore three antiviral agents with activity against monkeypox and other orthopoxviruses: cidofovir, brincidofovir, and tecovirimat. Cidofovir, and its prodrug brincidofovir, are inhibitors of DNA replication with a broad spectrum of activity against multiple families of double-stranded DNA viruses. Tecovirimat has more specific activity against orthopoxviruses, and inhibits the formation of the extracellular enveloped virus necessary for cell-to-cell transmission. For each agent, we review basic pharmacology, data from animal models and reported experience in human patients.

Considerations for Monkeypox Vaccination - CDC (Centers for Disease Control and Prevention, 2022)
Learn more about monkeypox in the United States.

Statin Use May Be Associated With a Lower Risk of Invasive Aspergillosis in Lung Transplant Recipients - Villalobos, Armelle Pérez Cortés; Foroutan, Farid; Davoudi, Setareh; Kothari, Sagar; Martinu, Tereza; Singer, Lianne G; Keshavjee, Shaf; Husain, Shahid (Clinical Infectious Diseases, 2022)
Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase) that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented.This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of 2 weeks duration prior to IA), adjusting for other known IA risk factors.We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). In total, 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (interquartile range [IQR]: 305 to 346). And 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (P = .002, SHR 0.30, 95% confidence interval [CI] 95% .14–.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs 123 (27%) in the statin group (P = .038).The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.

Risk factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant recipients: a multinational case-control study - Mejia-Chew, Carlos; Carver, Peggy L; Rutjanawech, Sasinuch; Camargo, Luis F Aranha; Fernandes, Ruan; Belga, Sara; Daniels, Shay Anne; Mueller, Nicolas J; Burkhard, Sara; Theodoropoulos, Nicole M; Postma, Douwe F; van Duijn, Pleun J; et al. (Clinical Infectious Diseases, 2022)
Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors.Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from January 1, 2008, to December 31, 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections.Analyses included 85 cases and 169 controls; (59% male, 88% white, median age at time of SOT of 54 years (IQR 40-62)). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < 0.05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI] 1.01-1.07), hospital admission within 90 days (aOR, 3.14; [1.41-6.98]), receipt of antifungals (aOR, 5.35; [1.7-16.91]), and lymphocyte-specific antibodies (aOR, 7.73, [1.07-56.14]), were associated with NTM infection.Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

A Consensus Conference to Define the Utility of Advanced Infectious Disease Diagnostics in Solid Organ Transplant Recipients - Azar, Marwan M.; Turbett, Sarah; Gaston, David; Gitman, Melissa; Razonable, Raymund; Koo, Sophia; Hanson, Kimberly; Kotton, Camille; Silveira, Fernanda; Banach, David B.; Basu, Sankha S.; Bhaskaran, Archana; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2022)
The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7th , 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

Antibiotics for Preventing Recurrent Urinary Tract Infection: Systematic Review and Meta-Analysis - Jent, Philipp; Berger, Julia; Kuhn, Annette; Trautner, Barbara W; Atkinson, Andrew; Marschall, Jonas (Open Forum Infectious Diseases, 2022)
Recurrent urinary tract infections (RUTI) are a common health problem. The only comprehensive synthesis on antibiotic prophylaxis in the last 15 years has been a guideline-embedded meta-analysis.We conducted a systematic review and meta-analysis of RCTs published up to 13 October 2020, evaluating patients ≥ 12 years with either ≥2 episodes of lower UTI within 6 months, or ≥ 3 in the past year. Placebo or antibiotics were allowed as comparators. Study quality was low.In the 11 placebo-controlled trials the risk for developing UTI was 85% lower with prophylaxis in comparison to placebo (RR 0.15, 95% CI 0.08-0.29).In the 9 head-to-head trials efficacy of antibiotic agents appeared similar: The pooled RR indicated no difference between nitrofurantoin and comparators [RR 1.01 (0.74-1.37)], nor trimethoprim (+/- sulfamethoxazole) [RR 1.34 (0.89-2.03)] or norfloxacin and comparators [RR 1.17 (0.43-1.70)].Studies comparing intermittent (post-coital) to continuous strategies revealed intermittent application as equally effective.

Mycobacterium abscessus Infections in Solid Organ Transplant Recipients: Single-Center Experience in the United States, 2013–2018 - Ebisu, Yosuke; Natori, Yoichiro; Rosello, Gemma; Anjan, Shweta; Simkins, Jacques; Camargo, Jose F; Morris, Michele I; Martinez, Octavio V; Abbo, Lilian M (Open Forum Infectious Diseases, 2022)
Mycobacterium abscessus is increasingly recognized as a human pathogen causing life-threatening infections in immunocompromised patients. There is a paucity of data around this topic in solid organ transplant (SOT) recipients.This work was a single-center retrospective cohort study of all SOT recipients with a positive culture for M abscessus between 2013 and 2018.A total of 20 patients (55% female) met inclusion criteria, including 1 kidney recipient (5.0%), 2 liver recipients (10.0%), 12 lung recipients (60.0%), 1 heart recipient (5.0%), and 4 combined organ recipients (20.0%). The median time from SOT to infection was 100 days (range, 30–431 days). Thirteen (65.0%) patients (1 kidney, 1 heart, 7 lung, 1 liver, 1 intestine, and 2 multivisceral) were treated with a median duration of 185 antibiotic days (range, 20–523 days). Among them, M abscessus was isolated from respiratory samples in 8 and nonrespiratory samples in 5; 4 of 13 (30.8%) patients had treatment failure and 3 of 13 (23.1%) had unrelated deaths within 1 year after diagnosis. Seven patients (5 lung transplant recipients) with the organism isolated from respiratory samples were not treated as their cultures represented airway colonization or contamination; of those, 2 (28.6%) died (unrelated to infection) and 5 (71.4%) were alive without the infection after 1 year of follow-up.Mycobacterium abscessus infections affect SOT recipients with a high proportion of clinical failures. However, in lung recipients, not all positive cultures correlated with infection, and without treatment some patients had good clinical outcomes. Thus, differentiating colonization from infection is important, and infection prevention measures and novel therapeutic agents are needed for SOT recipients.

Defining COVID-19–associated pulmonary aspergillosis: systematic review and meta-analysis - Kariyawasam, Ruwandi M.; Dingle, Tanis C.; Kula, Brittany E.; Vandermeer, Ben; Sligl, Wendy I.; Schwartz, Ilan S. (Clinical Microbiology and Infection, 2022)
Keywords: Aspergillus; CAPA; Fungal infection; ICU; Mycosis; SARS-CoV-2; Secondary infection

Monkeypox: A Contemporary Review for Healthcare Professionals - Titanji, Boghuma K; Tegomoh, Bryan; Nematollahi, Saman; Konomos, Michael; Kulkarni, Prathit A (Open Forum Infectious Diseases, 2022)
The ongoing 2022 multicountry outbreak of monkeypox is the largest in history to occur outside of Africa. Monkeypox is an emerging zoonotic disease that for decades has been viewed as an infectious disease with significant epidemic potential because of the increasing occurrence of human outbreaks in recent years. As public health entities work to contain the current outbreak, healthcare professionals globally are aiming to become familiar with the various clinical presentations and management of this infection. We present in this review an updated overview of monkeypox for healthcare professionals in the context of the ongoing outbreaks around the world.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective? - Zimmer, Andrea J; Stohs, Erica; Meza, Jane; Arnold, Christopher; Baddley, John W; Chandrasekar, Pranatharthi; El Boghdadly, Zeinab; Gomez, Carlos A; Maziarz, Eileen K; Montoya, Jose G; Pergam, Steven; Rolston, Kenneth V; et al. (Open Forum Infectious Diseases, 2022)
Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall.In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

American Society of Transplantation: COVID-19 Resources - AST (2022)

Transplanting thoracic COVID-19 positive donors: An institutional protocol and report of the first 14 cases - Eichenberger, Emily M.; Coniglio, Amanda C.; Milano, Carmelo; Schroder, Jacob; Bryner, Benjamin S.; Spencer, Philip J.; Haney, John C.; Klapper, Jacob; Glass, Carolyn; Pavlisko, Elizabeth; Dibernardo, Louis; Patel, Chetan B.; et al. (The Journal of Heart and Lung Transplantation, 2022)
We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.
Keywords: COVID-19; donor-derived infection; heart transplant; lung Transplant; organ donation

How I Treat and Prevent COVID-19 in Patients with Hematologic Malignancies and Recipients of Cellular Therapies - El Chaer, Firas; Auletta, Jeffery J; Chemaly, Roy F (Blood, 2022)
Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are more likely to experience severe coronavirus disease 2019 (COVID-19) and have a higher risk of morbidity and mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Compared to the general population, these patients have suboptimal humoral responses to COVID-19 vaccines and subsequently increased risk for breakthrough infections, underscoring the need for additional therapies, including pre- and post-exposure prophylaxis, to attenuate clinical progression to severe COVID-19. Therapies for COVID-19 are mostly available for adults and in the inpatient and outpatient settings. Selection and administration of the best treatment options are based on host factors; virus factors, including circulating SARS-CoV-2 variants; and therapeutic considerations, including the clinical efficacy, availability, and practicality of treatment and its associated side effects, including drug-drug interactions. In this paper, we discuss how we approach managing COVID-19 in patients with hematologic malignancies and recipients of HCT and cell therapy.

Challenges in the Treatment of Invasive Aspergillosis in Immunocompromised Children - Hsu, Alice J.; Tamma, Pranita D.; Fisher, Brian T. (Antimicrobial Agents and Chemotherapy, 2022)
Invasive aspergillosis (IA) is associated with signiﬁcant morbidity and mortality. Voriconazole remains the drug of choice for the treatment of IA in children; however, the complex kinetics of voriconazole in children make dosing challenging and therapeutic drug monitoring (TDM) essential for treatment success. The overarching goal of this review is to discuss the role of voriconazole, posaconazole, isavuconazole, liposomal amphotericin B, echinocandins, and combination antifungal therapy for the treatment of IA in children. We also provide a detailed discussion of antifungal TDM in children.

Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV - WHO (2022)
Cryptococcal disease is one of the most common opportunistic infections among people living with advanced HIV disease and is a major contributor to severe illness, morbidity, and mortality, particularly in sub-Saharan Africa. These guidelines update the recommendations that were first released in 2018 on diagnosing, preventing, and managing cryptococcal disease. In response to important new evidence that became available in 2021, these new guidelines strongly recommend a single high dose of liposomal amphotericin B as part of the preferred induction regimen for the treatment of cryptococcal meningitis in people living with HIV. This simplified regimen - a single high dose of liposomal amphotericin B paired with other standard medicines (flucytosine and fluconazole) - is as effective as the previous WHO standard of care, with the benefits of lower toxicity and fewer monitoring demands. The objective of these guidelines is to provide updated, evidence-informed recommendations for treating adults, adolescents and children living with HIV who have cryptococcal disease. These guidelines are aimed at HIV programme managers, policymakers, national treatment advisory boards, implementing partners and health-care professionals providing care for people living with HIV in resource-limited settings with a high burden of cryptococcal disease.

Coughing and Sneezing - CDC (Centers for Disease Control and Prevention, 2022)
Get information about how covering coughs and sneezes help prevent the spread of serious illnesses. Learn how to help stop the spread of germs.

Universal Lifelong Fungal Prophylaxis and Risk of Coccidioidomycosis in Lung Transplant Recipients Living in an Endemic Area - Truong, Clover N.; Nailor, Michael D.; Walia, Rajat; Cherrier, Lauren; Nasar, Aasya; Goodlet, Kellie J. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2022)
BACKGROUND: Lung transplant recipients residing in the endemic region are vulnerable to severe morbidity and mortality from Coccidioides. As infection risk persists beyond the first posttransplant year, investigations evaluating extended prophylaxis durations are needed. The purpose of this study is to assess the incidence of coccidioidomycosis among lung transplant recipients receiving universal lifelong azole antifungal prophylaxis. METHODS: Patients receiving transplants from 2013-2018 and initiated on azole antifungal prophylaxis at a lung transplant center in Arizona were included and followed through 2019 or until death, second transplant, or loss to follow-up. Recipients who died or received treatment for coccidioidomycosis during the transplant admission, or who had received a previous transplant, were excluded. The primary outcome was proven or probable coccidioidomycosis with new asymptomatic seropositivity assessed secondarily. RESULTS: A total of 493 lung transplant recipients were included, with 82% initiated on itraconazole prophylaxis, 9.3% on voriconazole, and 8.5% on posaconazole. Mean age at transplant was 62 years, 77% were diabetic, and 8% were seropositive for Coccidioides pretransplant. After a median follow-up of 31 months, 1 proven infection and 1 case of new asymptomatic seropositivity (1/493 each, 0.2% incidence) occurred during the study period. The single coccidioidomycosis case occurred 5 years posttransplant in a patient who had azole prophylaxis stopped several months prior. Although within-class switches were common throughout the study period, permanent discontinuation of azole prophylaxis was rare (1.4% at end of follow-up). CONCLUSIONS: Universal lifelong azole prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients residing in endemic regions.
Keywords: Antifungal Agents; Azoles; Coccidioides; Coccidioidomycosis; Humans; Lung; Retrospective Studies; Transplant Recipients; antifungal agents; endemic mycoses; immunocompromised host; itraconazole; transplant

National Landscape of Human Immunodeficiency Virus–Positive Deceased Organ Donors in the United States - Werbel, William A; Brown, Diane M; Kusemiju, Oyinkansola T; Doby, Brianna L; Seaman, Shanti M; Redd, Andrew D; Eby, Yolanda; Fernandez, Reinaldo E; Desai, Niraj M; Miller, Jernelle; Bismut, Gilad A; Kirby, Charles S; et al. (Clinical Infectious Diseases, 2022)
Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety.We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors.Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77–331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%–36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history.The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor–based regimens is rare, which is reassuring regarding safety.

Efficacy of Trimethoprim–Sulfamethoxazole in Combination with an Echinocandin as a First-Line Treatment Option for Pneumocystis Pneumonia: A Systematic Review and Meta-Analysis - Kato, Hideo; Hagihara, Mao; Asai, Nobuhiro; Umemura, Takumi; Shibata, Yuichi; Hirai, Jun; Yamagishi, Yuka; Iwamoto, Takuya; Mikamo, Hiroshige (Antibiotics, 2022)
Although combination therapy using trimethoprim–sulfamethoxazole (TMP–SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP–SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a systematic review and meta-analysis to compare the efficacies of these treatment options for PCP. The Scopus, EMBASE, PubMed, CINAHL, and Ichushi databases were searched for studies (up to January 2022) reporting the mortality and positive response rates (fewer clinical symptoms, improved partial pressure of arterial oxygen, and resolution of pneumonitis on chest imaging) of PCP patients receiving monotherapy or combination therapy. Four studies met the inclusion criteria. All four presented mortality data and one had positive response rates. Compared with the monotherapy, the combination therapy resulted in significantly lower mortality and higher positive response rates (mortality: odds ratio (OR) 2.20, 95% confidence interval (CI) 1.46–3.31; positive response rate: OR 2.13, 95%CI 1.41–3.23), suggesting it to be an effective and promising first-line therapy for PCP. However, further safety evaluations are needed to establish this as a fact.
Keywords: combination therapy; echinocandin; meta-analysis; pneumocystis pneumonia; trimethoprim–sulfamethoxazole

Hyperammonemia syndrome in immunosuppressed individuals - Roberts, Scott C.; Malik, Waleed; Ison, Michael G. (Current Opinion in Infectious Diseases, 2022)
Purpose of review Hyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients. Growing evidence suggests hyperammonemia syndrome is associated with systemic infections caused by urease-producing organisms, namely Ureaplasma spp., an organism unable to grow with routine culturing techniques. This review will summarize the epidemiology and clinical manifestations of hyperammonemia syndrome, as well as diagnostic and management strategies once hyperammonemia syndrome is suspected. Recent findings Hyperammonemia syndrome is being described in increasing frequency in the solid organ transplant population. Morbidity and mortality, even with treatment, is high once hyperammonemia syndrome occurs. Surveillance studies indicate the prevalence of lung donor colonization with Ureaplasma spp. is high, suggesting screening and treatment may be of benefit. Antibiotic resistance is common, and rapid diagnostics can facilitate appropriate antimicrobial therapy in the peri-transplant period. Summary Hyperammonemia syndrome is most commonly seen in lung transplant recipients and has a high mortality rate once it occurs. Screening for Ureaplasma spp. should be considered in all lung transplant donors.

Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies - Hammarström, Helena; Krifors, Anders; Athlin, Simon; Friman, Vanda; Golestani, Karan; Hällgren, Anita; Otto, Gisela; Oweling, Sara; Pauksens, Karlis; Kinch, Amelie; Blennow, Ola (Clinical Infectious Diseases, 2022)
Abstract Background Recent studies have reported that reduced dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP) but data is lacking for patients with hematologic malignancies. Methods This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at six Swedish University Hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (ΔPaO2/FiO2) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30. Results Out of a total of 113 included patients, 80 patients received reduced dose, and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, neither before nor after controlling for potential confounders in an adjusted regression model (-13,6 mmHg [95% CI -56,7-29,5] and -9,4 mmHg, [95% CI -50.5-31.7], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups, 18% vs. 21% and 14% vs. 15%, respectively. Among patients with mild to moderate pneumonia, defined as PaO2/FiO2>200 mmHg, all 44 patients receiving reduced dose were alive at day 30. Conclusion In this cohort of 113 patients with hematologic malignancies, reduced dose TMP-SMX was effective and safe for treating mild to moderate PJP.

Results of Two Cases of Pig-to-Human Kidney Xenotransplantation - Montgomery, Robert A.; Stern, Jeffrey M.; Lonze, Bonnie E.; Tatapudi, Vasishta S.; Mangiola, Massimo; Wu, Ming; Weldon, Elaina; Lawson, Nikki; Deterville, Cecilia; Dieter, Rebecca A.; Sullivan, Brigitte; Boulton, Gabriella; et al. (New England Journal of Medicine, 2022)

Tracking Candida auris | Candida auris | Fungal Diseases | CDC (2022)
Information about tracking the emerging fungal pathogen, C. auris including case counts, where cases of C. auris exist, and information about clinical cases and probable cases of Candida auris

The role of diagnostics-driven antifungal stewardship in the management of invasive fungal infections: a systematic literature review - Chakrabarti, Arunaloke; Mohamed, Naglaa; Capparella, Maria Rita; Townsend, Andy; Sung, Anita H.; Yura, Renee; Muñoz, Patricia (Open Forum Infectious Diseases, 2022)
Abstract Antifungal stewardship (AFS) programs are key to optimize antifungal use and improve outcomes in patients with invasive fungal infections. Our systematic literature review evaluated the impact of diagnostics in AFS programs by assessing performance and clinical measures. Most eligible studies were from Europe and US (n = 12/17). Diagnostic approaches included serum β-1–3-D-glucan test (n/N studies, 7/17), galactomannan test (4/17), CT scan (3/17), magnetic resonance (2/17), MALDI-TOF MS (2/17), PCR (1/17), PNA-FISH assay (1/17), and other routine methods (9/17). Time to species identification reduced significantly using MALDI-TOF and PNA FISH (n = 2). Time to targeted therapy and length of empiric therapy also decreased (n = 3). Antifungal consumption reduced by 11.6%-59.0% (7/13). Cost-savings ranged from 13.5%-50.6% (5/10). Mortality rate (13/16) and length of stay (6/7) also reduced. No negative impact reported on patient outcomes. Diagnostics-driven interventions can potentially improve AFS measures (antifungal consumption, cost, mortality, and LOS), therefore AFS implementation should be encouraged.

Utility of Cytomegalovirus Cell-Mediated Immunity Assays in Solid Organ Transplantation - Hall, Victoria G.; Humar, Atul; Kumar, Deepali (Journal of Clinical Microbiology, 2022)

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement - Spellberg, Brad; Aggrey, Gloria; Brennan, Meghan B.; Footer, Brent; Forrest, Graeme; Hamilton, Fergus; Minejima, Emi; Moore, Jessica; Ahn, Jaimo; Angarone, Michael; Centor, Robert M.; Cherabuddi, Kartikeya; et al. (JAMA Network Open, 2022)
Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence.To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools.This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group’s charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available.Sixty-three participants with diverse expertise from 8 countries developed the group’s charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy.The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Fact Sheets (English and Spanish) | Healthy Swimming | Healthy Water | CDC - CDC (2022)

Impact of COVID-19 on the antifungal susceptibility profiles of isolates collected in a global surveillance program that monitors invasive fungal infections - Pfaller, Michael A; Carvalhaes, Cecilia G; DeVries, Sean; Rhomberg, Paul R; Castanheira, Mariana (Medical Mycology, 2022)
Studies demonstrated the impact of the COVID-19 pandemic in the prevalence and susceptibility profiles of bacterial and fungal organisms. We analyzed 4821 invasive fungal isolates collected during 2018, 2019, and 2020 in 48 hospitals worldwide to evaluate the impact of this event in the occurrence and susceptibility rates of common fungal species. Isolates were tested using the CLSI broth microdilution method. While the percentage of total isolates that were C. glabrata (n = 710 isolates) or C. krusei (n = 112) slightly increased in 2020, the percentage for C. parapsilosis (n = 542), A. fumigatus (n = 416), and C. lusitaniae (n = 84) significantly decreased (P < .05). Fluconazole resistance in C. glabrata decreased from 5.8% in 2018–2019 to 2.0% in 2020, mainly due to fewer hospitals in the US having these isolates (5 vs. 1 hospital). Conversely, higher fluconazole-resistance rates were noted for C. parapsilosis (13.9 vs. 9.8%) and C. tropicalis (3.5 vs. 0.7%; P < .05) during 2020. Voriconazole resistance also increased for these species. Echinocandin resistance was unchanged among Candida spp. Voriconazole susceptibility rates in A. fumigatus were similar in these two periods (91.7% in 2018 and 2019 vs. 93.0% in 2020). Changes were also noticed in the organisms with smaller numbers of collected isolates. We observed variations in the occurrence of organisms submitted to a global surveillance and the susceptibility patterns for some organism-antifungal combinations. As the COVID-19 pandemic is still ongoing, the impact of this event must continue to be monitored to guide treatment of patients affected by bacterial and fungal infections.

Integrated Immunologic Monitoring in Solid Organ Transplantation: the Road Towards Torque Teno Virus-guided Immunosuppression - Jaksch, Peter; Görzer, Irene; Puchhammer-Stöckl, Elisabeth; Bond, Gregor (Transplantation, 2022)
Potent immunosuppressive drugs have been introduced into clinical care for solid organ transplant recipients. It is now time to guide these drugs on an individual level to optimize their efficacy. An ideal tool simultaneously detects overimmunosuppression and underimmunosuppression, is highly standardized, and is straightforward to implement into routine. Randomized controlled interventional trials are crucial to demonstrate clinical value. To date, proposed assays have mainly focused on the prediction of rejection and were based on the assessment of few immune compartments. Recently, novel tools have been introduced based on a more integrated approach to characterize the immune function and cover a broader spectrum of the immune system. In this respect, the quantification of the plasma load of a highly prevalent and apathogenic virus that might reflect the immune function of its host has been proposed: the torque teno virus (TTV). Although TTV control is driven by T cells, other major immune compartments might contribute to the hosts’ response. A standardized in-house polymerase chain reaction and a conformité européenne-certified commercially available polymerase chain reaction are available for TTV quantification. TTV load is associated with rejection and infection in solid organ transplant recipients, and cutoff values for risk stratification of such events have been proposed for lung and kidney transplantation. Test performance of TTV load does not allow for the diagnosis of rejection and infection but is able to define at-risk patients. Hitherto TTV load has not been used in interventional settings, but two interventional randomized controlled trials are currently testing the safety and efficacy of TTV-guided immunosuppression.

Safe Living After Transplant - Food, animals, and outdoors - Power2Save (American Society of Transplantation, 2022)
Make a difference in the field of transplantation by donating to support our cause.

Risk of SARS-CoV-2 transmission through solid organ transplantation and outcomes of COVID-19 among recent transplant recipients - Free, Rebecca J.; Annambhotla, Pallavi; La Hoz, Ricardo M.; Danziger-Isakov, Lara; Jones, Jefferson M.; Wang, Lijuan; Sankthivel, Senthil; Levi, Marilyn E.; Michaels, Marian G.; Kuhnert, Wendi; Klassen, David; Basavaraju, Sridhar V.; et al. (Open Forum Infectious Diseases, 2022)
SARS-CoV-2 is transmissible through lung transplantation, and outcomes among SARS-CoV-2-infected solid organ transplant (SOT) recipients may be severe; however, transmission risk to extrapulmonary organ recipients and recent (within 30 days of transplantation) SARS-CoV-2-infected recipient outcomes are unclear.During March 2020-March 2021, potential SARS-CoV-2 transmissions through SOT reported to the Organ Procurement and Transplantation Network were investigated. Laboratory and epidemiologic assessments included SARS-CoV-2 testing, medical record review, determination of likely transmission route, and recent SOT recipient outcomes.During March 2020-March 2021, ∼42,740 organs including ∼2,736 lungs were transplanted in the United States. Forty donors (37 deceased), who donated 140 organs to 125 recipients, were investigated. Nine (23%) donors and 25 (20%) recipients were SARS-CoV-2-positive by nucleic acid amplification testing (NAAT). Most (22/25, 88%) SARS-CoV-2-infected recipients had exposures in healthcare or community settings. Nine SARS-CoV-2-infected donors donated 21 organs (including three bilateral lungs) to 19 recipients. Of these, three lung recipients acquired SARS-CoV-2 infections from donors who were SARS-CoV-2-negative based on testing of pretransplant upper respiratory tract specimens but from whom posttransplant lower respiratory tract (LRT) specimens tested positive for SARS-CoV-2; one recipient died. Sixteen recipients of extrapulmonary organs from SARS-CoV-2-infected donors had no evidence of posttransplant COVID-19. All-cause mortality within 45-days after transplantation was six-fold higher among SARS-CoV-2-infected recipients (9/25, 36%) than without (6/100, 6%).SARS-CoV-2 transmission through SOT is uncommon. Pretransplant NAAT of lung donor LRT specimens may prevent transmission of SARS-CoV-2 via lung transplantation. Extrapulmonary organs from SARS-CoV-2-infected donors may be safely usable, although further study is needed. Given the high mortality, reducing recent recipient exposures to SARS-CoV-2 should remain a focus of prevention.

Primary Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients Receiving Rituximab - Park, Jun Won; Curtis, Jeffrey R.; Jun, Kang Il; Kim, Tae Min; Heo, Dae Seog; Ha, Jongwon; Suh, Kyung-Suk; Lee, Kwang-Woong; Lee, Hajeong; Yang, Jaeseok; Kim, Min Jung; Choi, Yunhee; et al. (CHEST, 2022)
Background Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified. Research Question Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis? Study Design and Methods This retrospective study included 3,524 patients (hematologic diseases, 2,500; rheumatic diseases, 559; pre/post-solid organ transplantation, 465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n = 2,523) and a prophylaxis group (n = 1,001) according to the administration of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) during the first 28 days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). The primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. The secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX. Results Over 2,759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted subdistribution hazard ratio, 0.20 [95% CI, 0.10-0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (adjusted subdistribution hazard ratio, 0.01 [0.003-0.16]). The incidence of ADRs related to TMP-SMX was 18.1 (14.6-22.2)/100 person-years, and most were of mild to moderate severity. On the basis of 10 severe ADRs, the number needed to harm was 101 (61.9-261.1), whereas the number needed to prevent one PJP infection was 32 (24.8-39.4). Interpretation TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.

Anal Human Papillomavirus Infection in Kidney Transplant Recipients Compared With Immunocompetent Controls - Larsen, Helle Kiellberg; Kjaer, Susanne K.; Haedersdal, Merete; Kjaer, Alexander K.; Bonde, Jesper Hansen; Sørensen, Søren Schwartz; Thomsen, Louise T. (Clinical Infectious Diseases, 2022)
Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)–related anogenital (pre)cancers, including anal high-grade intraepithelial lesions and cancer. Previous studies on anal high-risk HPV (hrHPV) among KTRs are sparse.In a cross-sectional study, we included 247 KTRs and 248 controls from a dermatology department and 5 nephrology departments in Denmark during 2016–2017. All participants provided an anal cytobrush sample that was tested for HPV DNA. Participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of anal hrHPV in KTRs compared with controls and risk factors for anal hrHPV in KTRs.The anal hrHPV prevalence was higher in female KTRs (45.5%) than in controls (27.2%). Female KTRs had almost 3-fold higher adjusted odds of anal hrHPV than controls (adjusted OR, 2.87 [95% confidence interval, 1.57–5.22]). In contrast, among men we did not observe increased prevalence or odds of anal hrHPV in KTRs compared with controls (prevalence, 19.4% vs 23.6%; adjusted OR, 0.85 [95% 95% confidence interval, .44–1.64]). Among hrHPV-positive KTRs, 63% and 52% of men and women, respectively, were infected with hrHPV types covered by the nonavalent HPV vaccine (type 16, 18, 31, 33, 45, 52, or 58). Current smoking, >10 lifetime sexual partners, history of genital warts, and among men having had receptive anal sex were risk factors for anal hrHPV in KTRs.Female KTRs had an increased risk of anal hrHPV compared with immunocompetent controls. Our findings indicate that pretransplant HPV vaccination should be considered to prevent anal high-grade intraepithelial lesions and cancer caused by anal hrHPV infection in KTRs.

Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa) - Tamma, Pranita D.; Aitken, Samuel L.; Bonomo, Robert A.; Mathers, Amy J.; van Duin, David; Clancy, Cornelius J. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2022)
BACKGROUND: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. The initial guidance document on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa) was published on September 17th, 2020. Over the past year, there have been a number of important publications furthering our understanding of the management of ESBL-E, CRE, and DTR-P. aeruginosa infections, prompting a rereview of the literature and this updated guidance document. METHODS: A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections reviewed, updated, and expanded previously developed questions and recommendations about the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. RESULTS: Preferred and alternative treatment recommendations are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Recommendations apply for both adult and pediatric populations. CONCLUSIONS: The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of October 24th, 2021. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance/.
Keywords: Antimicrobial resistance; cefiderocol; ceftazidime-avibactam; ceftolozane-tazobactam; imipenem-cilastatin-relebactam; meropenem-vaborbactam

Fluconazole-resistant Candida parapsilosis clonally related genotypes: first report proving the presence of endemic isolates harbouring the Y132F ERG11 gene substitution in Spain - Alcoceba, Eva; Gómez, Ana; Lara-Esbrí, Paula; Oliver, Antonio; Beltrán, Adrián Ferre; Ayestarán, Ignacio; Muñoz, Patricia; Escribano, Pilar; Guinea, Jesús (Clinical Microbiology and Infection, 2022)
Keywords: Candida parapsilosis; EUCAST E.Def 7.2.3; Fluconazole; Resistance; Y132F

Immunogenicity and Risk Factors Associated With Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant - Manothummetha, Kasama; Chuleerarux, Nipat; Sanguankeo, Anawin; Kates, Olivia S.; Hirankarn, Nattiya; Thongkam, Achitpol; Dioverti-Prono, M. Veronica; Torvorapanit, Pattama; Langsiri, Nattapong; Worasilchai, Navaporn; Moonla, Chatphatai; Plongla, Rongpong; et al. (JAMA Network Open, 2022)
This systematic review and meta-analysis assesses the current evidence on vaccine response and risk factors associated with diminished immune response in recipients of solid organ transplant.

Utility of Broad-Range PCR Sequencing for Infectious Diseases Clinical Decision Making: a Pediatric Center Experience - Naureckas Li, Caitlin; Nakamura, Mari M. (Journal of Clinical Microbiology, 2022)

European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine) - Paul, Mical; Carrara, Elena; Retamar, Pilar; Tängdén, Thomas; Bitterman, Roni; Bonomo, Robert A.; Waele, Jan de; Daikos, George L.; Akova, Murat; Harbarth, Stephan; Pulcini, Celine; Garnacho-Montero, José; et al. (Clinical Microbiology and Infection, 2022)
Keywords: Acinetobacter baumannii; Carbapenem-resistant bacteria; ESCMID; GRADE; Multidrug resistant bacteria

Solid Organ Transplantation From Donors With COVID-19 Infection - Boan, Peter; Marinelli, Tina; Opdam, Helen (Transplantation, 2022)
An abstract is unavailable.

Pretransplant Patient Education in Solid-organ Transplant: A Narrative Review - Hamid, Marzan; Rogers, Emma; Chawla, Gaauree; Gill, Jasleen; Macanovic, Sara; Mucsi, Istvan (Transplantation, 2022)
Education for pretransplant, solid-organ recipient candidates aims to improve knowledge and understanding about the transplant process, outcomes, and potential complications to support informed, shared decision-making to reduce fears and anxieties about transplant, inform expectations, and facilitate adjustment to posttransplant life. In this review, we summarize novel pretransplant initiatives and approaches to educate solid-organ transplant recipient candidates. First, we review approaches that may be common to all solid-organ transplants, then we summarize interventions specific to kidney, liver, lung, and heart transplant. We describe evidence that emphasizes the need for multidisciplinary approaches to transplant education. We also summarize initiatives that consider online (eHealth) and mobile (mHealth) solutions. Finally, we highlight education initiatives that support racialized or otherwise marginalized communities to improve equitable access to solid-organ transplant. A considerable amount of work has been done in solid-organ transplant since the early 2000s with promising results. However, many studies on education for pretransplant recipient candidates involve relatively small samples and nonrandomized designs and focus on short-term surrogate outcomes. Overall, many of these studies have a high risk of bias. Frequently, interventions assessed are not well characterized or they are combined with administrative and data-driven initiatives into multifaceted interventions, which makes it difficult to assess the impact of the education component on outcomes. In the future, well-designed studies rigorously assessing well-defined surrogate and clinical outcomes will be needed to evaluate the impact of many promising initiatives.

Novel factors to predict respiratory viral disease progression in allogeneic hematopoietic cell transplant recipients - Ogimi, Chikara; Xie, Hu; Waghmare, Alpana; Jerome, Keith R.; Leisenring, Wendy M.; Ueda Oshima, Masumi; Carpenter, Paul A.; Englund, Janet A.; Boeckh, Michael (Bone Marrow Transplantation, 2022)
We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008–9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of  >1 transplant, age  ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7–12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.
Keywords: Epidemiology; Risk factors

Tackling the emerging threat of antifungal resistance to human health - Fisher, Matthew C.; Alastruey-Izquierdo, Ana; Berman, Judith; Bicanic, Tihana; Bignell, Elaine M.; Bowyer, Paul; Bromley, Michael; Brüggemann, Roger; Garber, Gary; Cornely, Oliver A.; Gurr, Sarah. J.; Harrison, Thomas S.; et al. (Nature Reviews Microbiology, 2022)
Invasive fungal infections pose an important threat to public health and are an under-recognized component of antimicrobial resistance, an emerging crisis worldwide. Across a period of profound global environmental change and expanding at-risk populations, humaninfecting pathogenic fungi are evolving resistance to all licensed systemic antifungal drugs. In this Review, we highlight the main mechanisms of antifungal resistance and explore the similarities and differences between bacterial and fungal resistance to antimicrobial control. We discuss the research and innovation topics that are needed for risk reduction strategies aimed at minimizing the emergence of resistance in pathogenic fungi. These topics include links between the environment and One Health, surveillance, diagnostics, routes of transmission, novel therapeutics and methods to mitigate hotspots for fungal adaptation. We emphasize the global efforts required to steward our existing antifungal armamentarium, and to direct the research and development of future therapies and interventions.

Impact of different urinary tract infection phenotypes within the first year post‐transplant on renal allograft outcomes - Brune, Jakob E.; Dickenmann, Michael; Wehmeier, Caroline; Sidler, Daniel; Walti, Laura; Golshayan, Dela; Manuel, Oriol; Hadaya, Karine; Neofytos, Dionysios; Schnyder, Aurelia; Boggian, Katia; Müller, Thomas; et al. (American Journal of Transplantation, 2022)

Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis - Jarvis, Joseph N.; Lawrence, David S.; Meya, David B.; Kagimu, Enock; Kasibante, John; Mpoza, Edward; Rutakingirwa, Morris K.; Ssebambulidde, Kenneth; Tugume, Lillian; Rhein, Joshua; Boulware, David R.; Mwandumba, Henry C.; et al. (New England Journal of Medicine, 2022)

Toward Simpler, Safer Treatment of Cryptococcal Meningitis - Moosa, Mahomed-Yunus S.; Lessells, Richard J. (New England Journal of Medicine, 2022)
Cryptococcal meningitis is one of the most common and serious human immunodeficiency virus (HIV)–related opportunistic infections among adults in sub-Saharan Africa, leading to an estimated 135,900 deaths every year.1 Under the best conditions, cryptococcal meningitis is a challenge to manage and involves high-quality medical and nursing care and often prolonged hospitalization. Much of this is driven by the fact that the best outcomes are seen when the key antifungal agent, amphotericin B, is administered intravenously daily for 1 or 2 weeks.2 However, treatment with amphotericin B–based regimens frequently results in substantial toxic effects, including blood dyscrasias, acute kidney injury, electrolyte . . .

Mycoplasma hominis infections in solid organ transplant recipients: Clinical characteristics, treatment outcomes, and comparison of phenotypic and genotypic susceptibility profiles - Chang, Sandy Y.; Price, Travis K.; Beaird, Omer E.; Gaynor, Pryce T.; Schaenman, Joanna M.; Carlson, Margrit E.; Kubak, Bernard M.; Yang, Shangxin; Multani, Ashrit (Transplant Infectious Disease, 2022)
Background: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M. hominis isolates identified from SOT patients. Methods: This is a single-center retrospective study evaluating SOT recipients with confirmed M. hominis infections. Patients’ demographic, clinical, microbiological, and radiographic data were collected. Culture of M. hominis isolates was performed according to current Clinical and Laboratory Standards Institute guidelines. Phenotypic susceptibility testing was performed by University of Alabama Diagnostic Mycoplasma Laboratory. Whole genome sequencing (WGS) was performed followed by bioinformatic analysis of known genetic determinants of resistance. Results: Seven SOT recipients with M. hominis infections were identified. Two out of seven (28.5%) patients had resistance detected by phenotypic susceptibility testing (Case 5 to levofloxacin and Case 7 to tetracycline). Genomic analyses confirmed the presence of mutations in the parC and parE topoisomerase genes at positions conferring to fluoroquinolone resistance in the isolate from Case 5, while the tetracycline-resistant isolate from Case 7 harbored the tetM gene. The median TAT from the date of specimen collection was 24 days for phenotypic susceptibility testing and 14 days for genotypic susceptibility testing. All seven patients received antimicrobials directed toward M. hominis and recovered with complete resolution of infection. Conclusions: WGS may offer a novel and more rapid methodology for M. hominis susceptibility testing to help optimize antimicrobial usage, but more data are needed.

Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated With Antithymocyte Globulin: A Randomized Clinical Trial - Páez-Vega, Aurora; Gutiérrez-Gutiérrez, Belén; Agüera, Maria L; Facundo, Carme; Redondo-Pachón, Dolores; Suñer, Marta; López-Oliva, Maria O; Yuste, Jose R; Montejo, Miguel; Galeano-Álvarez, Cristina; Ruiz-San Millan, Juan C; Los-Arcos, Ibai; et al. (Clinical Infectious Diseases, 2022)
Background. Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. Methods.  In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). Results.  A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Conclusions.  Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. Clinical Trials Registration. NCT03123627.

Non-invasive Testing and Surrogate Markers in Invasive Fungal Diseases - Thompson, George R; Boulware, David R; Bahr, Nathan C; Clancy, Cornelius J; Harrison, Thomas S; Kauffman, Carol A; Le, Thuy; Miceli, Marisa H; Mylonakis, Eleftherios; Nguyen, Hong; Ostrosky-Zeichner, Luis; Patterson, Thomas F; et al. (Open Forum Infectious Diseases, 2022)
Abstract Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandates the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival endpoints may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.

Immune control of cytomegalovirus reactivation in stem cell transplantation - Degli-Esposti, Mariapia A.; Hill, Geoffrey R. (Blood, 2022)
Abstract The reactivation of viruses from latency after allogeneic stem cell transplantation (SCT) continues to represent a major clinical challenge requiring sophisticated monitoring strategies in the context of prophylactic and/or preemptive antiviral drugs that are associated with significant expense, toxicity and rates of failure. Accumulating evidence has demonstrated the association of polyfunctional virus-specific T cells with protection from viral reactivation, affirmed by the ability of adoptively transferred virus-specific T cells to prevent and treat reactivation and disease. The roles of natural killer cells in early viral surveillance and of dendritic cells in priming of T cells have also been delineated. Most recently, a role for strain-specific humoral responses in preventing early cytomegalovirus (CMV) reactivation has been demonstrated in preclinical models. Despite these advances, many unknowns remain: what are the critical innate and adaptive responses over time; are the origin (eg, recipient vs donor) and localization (eg, in parenchymal tissue vs lymphoid organs) of these responses important; how does graft-versus-host disease and the prevention and treatment thereof (eg, high-dose steroids) affect the functionality and relevance of a particular immune axis; do the immune parameters that control latency, reactivation, and dissemination differ; and what is the impact of new antiviral drugs on the development of enduring antiviral immunity. Thus, although antiviral drugs have provided major improvements over the past two decades, understanding the immunological paradigms underpinning protective antiviral immunity after SCT offers the potential to generate nontoxic, immune-based therapeutic approaches for lasting protection from viral reactivation.

Antibiotic Stewardship and Inpatient Clostridioides difficile Testing in Solid Organ Transplant Recipients: The Need for Multilevel Checks and Balances - Kueht, Michael; Kharsa, Ahmad; Mujtaba, Muhammad; Kulkarni, Rupak; Britt, Rachel; Lea, A. Scott; Hafiz, Ghani; Fair, Jeffery; Reynoso, David (Transplantation Proceedings, 2022)
Background Diarrhea among recipients of solid organ transplants is a commonly encountered problem and is often multifactorial in etiology. Owing to the combination of perioperative antibiotic administration and the immunosuppressed status of transplant recipients, a high degree of suspicion for Clostridioides difficile (C. difficile) colitis is prudent. The purpose of this study is to demonstrate the association of an institutional integrated stewardship program with C. difficile testing practices after abdominal solid organ transplantation. Methods Starting in July 2017, a diagnostic stewardship was enacted in our institution requiring the ordering provider to answer a series of questions within the electronic medical record before ordering a C. difficile toxin test. The charts were reviewed for all solid organ transplant recipients on whom a test was ordered between January 2016 and September 2019. Results Orders for C. difficile toxin per quarter significantly decreased in the postintervention era (18 vs 8.5, P = .038). Median cost of inpatient treatment and days of therapy per thousand patient days was significantly lower in the postintervention era (median cost, $2,944.55 vs $416.92; P = .01) (days of therapy per thousand patient days, 521.9 vs 300.5; P < .01). Quarterly rates of negative tests were similar between the pre- and postintervention eras (65% vs 73%, P = .38). Conclusions Although no orders were blocked based on the responses, this multilevel intervention was associated with a 47% decrease in C. difficile testing without effecting the rate of negative testing. These results suggest that we have achieved significant cost savings, in testing and isolation, without sacrificing critical aspects of clinical care.

Toxoplasmosis after allogeneic haematopoietic cell transplantation: experience using a PCR-guided pre-emptive approach - Aerts, Robina; Mercier, Toine; Beckers, Mariëlle; Schoemans, Hélène; Lagrou, Katrien; Maertens, Johan (Clinical Microbiology and Infection, 2022)
Keywords: Allogeneic haematopoietic cell transplantation; Anti-Toxoplasmaprophylaxis; PCR; Pre-emptive approach; Toxoplasma gondii; Toxoplasmosis; Trimethoprim–sulphamethoxazole

Efficacy of Noncarbapenem β-Lactams Compared to Carbapenems for Extended-Spectrum β-Lactamase–Producing Enterobacterales Urinary Tract Infections - Anderson, Daniel T; Albrecht, Benjamin; Jones, K Ashley; Jacob, Jesse T; Sexton, Mary Elizabeth; Wiley, Zanthia; Dube, William C; Lee, Benjamin; Suchindran, Sujit (Open Forum Infectious Diseases, 2022)
Abstract Background Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are frequent causes of urinary tract infections (UTIs). Severe infections caused by ESBL Enterobacterales are often treated with carbapenems, but optimal treatment for less severe infections such as UTIs is unclear. Methods This retrospective cohort study included patients admitted to 4 hospitals in an academic healthcare system with an ESBL UTI treated with either a noncarbapenem β-lactam (NCBL) or a carbapenem for at least 48 hours from 1 April 2014 to 30 April 2018. Those who received an NCBL were compared to those receiving a carbapenem, with a primary outcome of hospital length of stay (LOS) and secondary outcomes of clinical and microbiological response, days until transition to oral therapy, rate of relapsed infection, and rate of secondary infections with a multidrug-resistant organism. Results Characteristics were similar among patients who received carbapenems (n = 321) and NCBLs (n = 171). There was no difference in LOS for the NCBL group compared to the carbapenem group (13 days vs 15 days, P = .66). The NCBL group had higher rates of microbiologic eradication (98% vs 92%, P = .002), shorter time to transition to oral therapy (5 days vs 9 days, P < .001), shorter overall durations of therapy (7 days vs 10 days, P < .001), and lower rates of relapsed infections (5% vs 42%, P = .0003). Conclusions Patients treated with NCBLs had similar LOS, higher rates of culture clearance, and shorter durations of antibiotic therapy compared to patients treated with carbapenems, suggesting that treatment for ESBL UTIs should not be selected solely based on phenotypic resistance.

Omitting Ciprofloxacin Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation and Its Impact on Clinical Outcomes and Microbiome Structure - Daoud-Asfour, Haneen; Henig, Israel; Ghersin, Itai; Rakedzon, Stav; Stern, Anat; Pitashny, Milena; Zuckerman, Tsila; Bar-Yoseph, Haggai (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2022)
Keywords: Allogeneic hematopoietic stem cell transplantation; Ciprofloxacin; Graft-versus-host disease; Microbiome; Prophylaxis

Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplantation Patients - Gardner, Julia C.; Courter, Joshua D.; Dandoy, Christopher E.; Davies, Stella M.; Teusink-Cross, Ashley (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2022)
Keywords: Acute graft-versus-host disease; Bloodstream infection prophylaxis; Clostridioides difficile; Hematopoietic stem cell transplantation; Levofloxacin; Multidrug-resistant organism

Donor-derived Ehrlichiosis: 2 Clusters Following Solid Organ Transplantation - Saha, Aditi; Browning, Charles; Dandamudi, Raja; Barton, Kevin; Graepel, Kevin; Cullity, Madeline; Abusalah, Wala; Christine, Du; Rossi, Carla; Drexler, Naomi; Basavaraju, Sridhar V; Annambhotia, Pallavi; et al. (Clinical Infectious Diseases, 2022)
Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor-derived clusters of ehrlichiosis are described here. During the summer of 2020, 2 cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to the CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis. Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All 3 were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization and the OPTN for further investigation by public health authorities.

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience - Verlinden, Anke; Jansens, Hilde; Goossens, Herman; Anguille, Sébastien; Berneman, Zwi N; Schroyens, Wilfried A; Gadisseur, Alain P (Open Forum Infectious Diseases, 2022)
Abstract Background There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients. Methods We studied 446 admissions after introduction of an ECIL-4–based protocol (hereafter “ECIL-4 group”) in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption. Results Bacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P = .001) and 7 daily antibiotic doses (17 vs 24; P < .001) per admission period. Conclusions Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

Human Polyomavirus 9—An Emerging Cutaneous and Pulmonary Pathogen in Solid Organ Transplant Recipients - Mishra, Nischay; Ng, James; Strom, Mark A.; Jain, Komal; Thakkar, Riddhi; Joshi, Shreyas; Pereira, Marcus; Shah, Lori; Grossman, Marc E.; Lee, Michael J.; De Michele, Simona; Silvers, David N.; et al. (JAMA Dermatology, 2022)
This case series describes previously undescribed hyperkeratotic lesions, clinical decline, and fatality associated with human polyomavirus 9 in solid organ transplant recipients in a single university medical center.

Epidemiology of candidemia in lung transplant recipients and risk factors for candidemia in the early posttransplant period in the absence of universal antifungal prophylaxis - Marinelli, Tina; Pennington, Kelly M.; Hamandi, Bassem; Donahoe, Laura; Rotstein, Coleman; Martinu, Tereza; Husain, Shahid (Transplant Infectious Disease, 2022)
Background: Lung transplant recipients are at increased risk of candidemia, especially in the early posttransplant period. However, the specific predisposing factors have not been established. The natural history of candidemia after lung transplantation, in the absence of universal antifungal prophylaxis, is not known. Methods: We retrospectively examined the epidemiology of candidemia at any time posttransplant in patients who underwent lung transplantation at our center between 2016 and 2019. We undertook a case-control study and used logistic regression to evaluate the risk factors for candidemia during the first 30 days posttransplantation. Results: During the study period 712 lung transplants were performed on 705 patients. Twenty-five lung transplant recipients (LTRs) (3.5%) experienced 31 episodes of candidemia. The median time to candidemia was 19.5 days (IQR 10.5–70.5), with 61.2% (n = 19) episodes of candidemia occurring within the first 30 days posttransplantation. Pretransplant hospitalization, posttransplant ECMO, and posttransplant renal replacement therapy were associated with an increased risk of candidemia in the first 30 days posttransplant. Of those with candidemia in the first 30 days, 31.2% died within 30 days of the index positive blood culture. Candidemia was associated with decreased survival within 30 days posttransplant. Conclusion: This study highlights the greatest risk period of lung transplant recipients for development of candidemia and identifies several factors associated with increased risk of candidemia. These findings will help guide future studies on antifungal prophylaxis.

American Society for Transplantation and Cellular Therapy Series: #5 - Management of Clostridioides difficile infection in hematopoietic cell transplant recipients - Alonso, Carolyn D.; Maron, Gabriela; Kamboj, Mini; Carpenter, Paul A.; Gurunathan, Arun; Mullane, Kathleen; Dubberke, Erik R. (Transplantation and Cellular Therapy, 2022)
The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy (ASTCT) partnered with its Transplant Infectious Disease Special Interest Group (TID-SIG) to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables and figures.1 Adult and pediatric infectious disease and HCT content experts developed, then answered FAQs, and finalized topics with harmonized recommendations that were made by assigning an A through E strength of recommendation paired with a level of supporting evidence graded I through III. This fifth guideline in the series focuses on Clostridioides difficile infection with FAQs that address the prevalence, incidence, clinical features, colonization versus infection, clinical complications, diagnostic considerations, pharmacological therapies for episodic or recurrent infection, and the roles of prophylactic antibiotics, probiotics, and fecal microbiota transplantation.

Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients - Mehta, Nirja; Wang, Tiffany; Friedman-Moraco, Rachel J.; Carpentieri, Cynthia; Mehta, Aneesh K.; Rouphael, Nadine; Dhere, Tanvi; Larsen, Christian P.; Kraft, Colleen S.; Woodworth, Michael H. (Journal of Clinical Microbiology, 2022)
In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difﬁcile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI); however, guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss the current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.

Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine - Kumar, Deepali; Ferreira, Victor H.; Hall, Victoria G.; Hu, Queenie; Samson, Reuben; Ku, Terrance; Ierullo, Matthew; Majchrzak-Kita, Beata; Tomlinson, George; Gingras, Anne-Claude; Humar, Atul (Annals of Internal Medicine, 2022)

Clinical Characteristics and Outcomes of Patients With COVID-19–Associated Acute Respiratory Distress Syndrome Who Underwent Lung Transplant - Kurihara, Chitaru; Manerikar, Adwaiy; Querrey, Melissa; Felicelli, Christopher; Yeldandi, Anjana; Garza-Castillon, Rafael, Jr; Lung, Kalvin; Kim, Samuel; Ho, Bing; Tomic, Rade; Arunachalam, Ambalavanan; Budinger, G. R. Scott; et al. (JAMA, 2022)
Lung transplantation is a potentially lifesaving treatment for patients who are critically ill due to COVID-19–associated acute respiratory distress syndrome (ARDS), but there is limited information about the long-term outcome.To report the clinical characteristics and outcomes of patients who had COVID-19–associated ARDS and underwent a lung transplant at a single US hospital.Retrospective case series of 102 consecutive patients who underwent a lung transplant at Northwestern University Medical Center in Chicago, Illinois, between January 21, 2020, and September 30, 2021, including 30 patients who had COVID-19–associated ARDS. The date of final follow-up was November 15, 2021.Lung transplant.Demographic, clinical, laboratory, and treatment data were collected and analyzed. Outcomes of lung transplant, including postoperative complications, intensive care unit and hospital length of stay, and survival, were recorded.Among the 102 lung transplant recipients, 30 patients (median age, 53 years [range, 27 to 62]; 13 women [43%]) had COVID-19–associated ARDS and 72 patients (median age, 62 years [range, 22 to 74]; 32 women [44%]) had chronic end-stage lung disease without COVID-19. For lung transplant recipients with COVID-19 compared with those without COVID-19, the median lung allocation scores were 85.8 vs 46.7, the median time on the lung transplant waitlist was 11.5 vs 15 days, and preoperative venovenous extracorporeal membrane oxygenation (ECMO) was used in 56.7% vs 1.4%, respectively. During transplant, patients who had COVID-19–associated ARDS received transfusion of a median of 6.5 units of packed red blood cells vs 0 in those without COVID-19, 96.7% vs 62.5% underwent intraoperative venoarterial ECMO, and the median operative time was 8.5 vs 7.4 hours, respectively. Postoperatively, the rates of primary graft dysfunction (grades 1 to 3) within 72 hours were 70% in the COVID-19 cohort vs 20.8% in those without COVID-19, the median time receiving invasive mechanical ventilation was 6.5 vs 2.0 days, the median duration of intensive care unit stay was 18 vs 9 days, the median post–lung transplant hospitalization duration was 28.5 vs 16 days, and 13.3% vs 5.5% required permanent hemodialysis, respectively. None of the lung transplant recipients who had COVID-19–associated ARDS demonstrated antibody-mediated rejection compared with 12.5% in those without COVID-19. At follow-up, all 30 lung transplant recipients who had COVID-19–associated ARDS were alive (median follow-up, 351 days [IQR, 176-555] after transplant) vs 60 patients (83%) who were alive in the non–COVID-19 cohort (median follow-up, 488 days [IQR, 368-570] after lung transplant).In this single-center case series of 102 consecutive patients who underwent a lung transplant between January 21, 2020, and September 30, 2021, survival was 100% in the 30 patients who had COVID-19–associated ARDS as of November 15, 2021.

A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients with Hematological Malignancies - Chaftari, Anne-Marie; Hachem, Ray; Malek, Alexandre E; Mulanovich, Victor; Szvalb, Ariel; Jiang, Ying; Yuan, Ying; Ali, Shahnoor; Deeba, Rita; Chaftari, Patrick; Raad, Issam (Open Forum Infectious Diseases, 2022)
Abstract Background With increased use of antibiotics in high risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial (NCT03485950), we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard-of-care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies. Methods We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21-28), and late follow-up (LFU; days 35-42). Results We analyzed 47 C/T patients and 50 SOC patients. C/T patients had a higher rate of favorable clinical response at EOIV (87% vs 72%). A one-sided non-inferiority analysis indicated that C/T was at least not inferior to the SOC for favorable clinical response at EOIV (p=0.002), TOC (p=0.004) and LFU (p=0.002). Superiority tests showed that C/T led to significantly lower rates of clinical failure at TOC (6% vs 30%; p=0.003) and LFU (9% vs 30%; p=0.008). C/T and SOC patients with documented infections had similar rates of favorable microbiological response. Serious adverse events leading to drug discontinuation (2% vs 0%; p=0.48), and overall mortality (6% vs 4%; p=0.67) were similar in both groups. Conclusions The empiric use of C/T in high-risk patients with hematological malignancies and febrile neutropenia is safe and associated with better clinical outcomes than SOC antimicrobial agents.

Applying mucosal barrier injury laboratory-confirmed bloodstream infection criteria in patients with solid tumors and hematologic malignancies: A retrospective cohort study looking for the real source of infection - Puin da Silva, Ana Carolina; Vieira, Michely Fernandes; Freire, Maristela Pinheiro; Vaz, Lumena; Bonazzi, Patrícia Rodrigues; Ibrahim, Karim Yaqub; Diz, Maria Del Pilar Esteves; Hoff, Paulo Marcelo; Pereira, Juliana; Rocha, Vanderson Geraldo; Abdala, Edson (Infection Control & Hospital Epidemiology, 2022)
We evaluated the interference of the mucosal barrier injury (MBI) laboratory-confirmed bloodstream infection (MBI-LCBI) criteria on the central-line–associated bloodstream infection (CLABSI) incidence density, and the proportion of catheter-related bloodstream infections (CRBSIs) among those classified as MBI. We detected 339 CLABSIs: 15.0% were classified as MBI-LCBIs, and among these, 19.6% were classified as CRBSIs.

The Case for Prolonged ECMO for COVID-19 ARDS as a Bridge to Recovery or Lung Transplantation - Bermudez, Christian A.; Crespo, Maria M. (Transplantation, 2022)

Serious and atypical presentations of Bartonella henselae infection in kidney transplant recipients - Bos, Feline; Chauveau, Bertrand; Ruel, Jules; Fontant, Gabriel; Campistron, Elise; Meunier, Camille; Jambon, Frédéric; Moreau, Karine; Delmas, Yahsou; Couzi, Lionel; Korbi, Skander; Charrier, Manon; et al. (Open Forum Infectious Diseases, 2022)
Description of five cases of bartonellosis with fever and atypical clinical presentations in kidney transplant recipients : thrombotic microangiopathies, recurrent haemophagocytosis and immune reconstitution syndrome after treatment. The diagnosis, the pathological lesions, and treatments are described. Bartonellosis must be researched in solid organ transplant recipients with fever of Accepted Manuscript undeterminedorigin.

Unexpected Cytomegalovirus (CMV) Replication Kinetics in CMV Donor-Seropositive, Recipient-Seronegative Liver Transplant Recipients Receiving Preemptive Antiviral Therapy - Singh, Nina; Winston, Drew J; Razonable, Raymund R; Marshall Lyon, G; Silveira, Fernanda P; Wagener, Marilyn M; Limaye, Ajit P (The Journal of Infectious Diseases, 2022)
Detailed cytomegalovirus (CMV) kinetics in donor CMV-seropositive, recipient CMV-seronegative (D+/R–) transplant recipients receiving preemptive therapy (PET) have not been fully defined.The study population consisted of the PET arm of a randomized CMV prevention trial in D+/R– liver transplant recipients. CMV DNA polymerase chain reaction (PCR) assays were performed weekly for 100 days using a sensitive assay. Viral load and clinical parameters were compared for patients with or without high-level increase (defined as higher than the group median log10 increase in viral load from baseline after PET initiation).Among 79 patients, 93.6% (74/79) developed an increase from baseline viral loads of median 120 IU/mL to 3350 IU/mL; 25.7% (19/74) of the patients had peak levels >10 000 IU/mL. None of the patients with rise in viral load underwent testing for CMV resistance, and viremia resolved with PET with valganciclovir. Patients with high-level increase in viral load had a significantly lower rate of recurrent viremia than those without such increase (16/40 [40%] vs 28/39 [71.8%], respectively; P = .004).A majority of D+/R– recipients had a marked increase in viral load after initiation of PET before resolution of viremia. This phenomenon is associated with lower rates of subsequent recurrent viremia and does not necessarily imply antiviral resistance.

Impact of donor multidrug-resistant organisms on solid organ transplant recipient outcomes - Anesi, Judith A.; Blumberg, Emily A.; Han, Jennifer H.; Lee, Dong Heun; Clauss, Heather; Hasz, Richard; Molnar, Esther; Alimenti, Darcy; Motzer, Andrew R.; West, Sharon; Bilker, Warren B.; Tolomeo, Pam; et al. (Transplant infectious disease : an official journal of the Transplantation Society, 2022)
Background: The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality. Methods: A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association. Results: Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01–2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15–1.36, p = .16). Conclusions: MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture maybe safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed.

Oral vancomycin for Clostridioides difficile prophylaxis in allogenic hematopoietic cell transplant - Altemeier, Olivia J.; Konrardy, Kelsey T. (Transplant Infectious Disease, 2022)
Background: Neutropenia and antibiotic use put patients at risk for Clostridioides difficile infection (CDI) following allogenic hematopoietic cell transplant (alloHCT). CDI following alloHCT has been associated with acute graft-versus-host disease (aGVHD), a significant cause of morbidity and mortality in this population. We sought to evaluate if prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients. Methods: We conducted a single-center retrospective chart review to compare the effectiveness of oral vancomycin prophylaxis versus no prophylaxis in alloHCT recipients at the University of Kansas Health System. Vancomycin for CDI prophylaxis was implemented in March of 2018 at the University of Kansas Health System. Review of 100 consecutive alloHCT patients before and after this implementation was used to compare outcomes. Patients received oral vancomycin 125 mg twice daily, starting on the day of inpatient admission for alloHCT and continued until discharge. The primary outcome is the incidence of CDI in patients with oral vancomycin prophylaxis compared to those who did not receive prophylaxis during hospital admission for alloHCT. The secondary endpoints include the incidence of acute grades 2–4 GVHD, and eventfree survival for each arm. Results: Eleven percent of patients developed CDI in the control group versus 2% of patients in the intervention group (p = .018). Oral vancomycin was not associated with a higher risk of acute GVHD grades 2–4 (36% vs. 38%; p = .77) at day 100 post transplant. No difference was seen in event-free survival. Conclusions: Oral vancomycin was associated with reduced CDI incidence in patients that underwent an alloHCT without negatively affecting posttransplant outcomes. The contribution of confounders cannot be excluded.

Daptomycin-Resistant Enterococcus Bacteremia Is Associated with Prior Daptomycin Use and Increased Mortality after Liver Transplantation - Lee, Rachael A; Goldman, Jason; Haidar, Ghady; Lewis, Jessica; Arif, Sana; Hand, Jonathan; La Hoz, Ricardo M; Pouch, Stephanie; Holaday, Eric; Clauss, Heather; Kaye, Keith S; Nellore, Anoma (Open Forum Infectious Diseases, 2022)
Risk factors for acquisition of vancomycin-resistant Enterococcus (VRE) include immunosuppression, antibiotic exposure, indwelling catheters, and manipulation of the gastrointestinal tract, all of which occur in liver transplant recipients. VRE infections are documented in liver transplantation (LT); however, only one single center study has assessed the impact daptomycin-resistant Enterococcus (DRE) in this patient population.We conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within one year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest.We identified 139 cases of Enterococcus bacteremia following LT, of which 78% were VRE and 22% were DRE. When adjusted for total ICU days in the first transplant year, liver-kidney transplantation, and calcineurin inhibitor use, patients with DRE bacteremia were 2.65 times more likely to die within one year of transplantation (aOR 2.648 [1.025-6.840], p = 0.044). Prior daptomycin exposure was found to be an independent predictor of DRE bacteremia (aOR 30.62 (10.087-92.955), p <0.001).In this multicenter study of LT recipients with Enterococcus bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared to VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 - Anderson, Tara C.; Masters, Nina B.; Guo, Angela; Shepersky, Leah; Leidner, Andrew J.; Lee, Grace M.; Kotton, Camille N.; Dooling, Kathleen L. (MMWR. Morbidity and Mortality Weekly Report, 2022)
What is already known about this topic? Immunocompromised persons experience a higher incidence of herpes zoster and related complications. On July 23, 2021, the Food and Drug Administration expanded the indication for use of recombinant zoster vaccine (RZV) to include immunodeficient or immunosuppressed adults. What is added by this report? On October 20, 2021, the Advisory Committee on Immunization Practices recommended 2 RZV doses for prevention of herpes zoster and related complications in immunodeficient or immunosuppressed adults aged ≥19 years. What are the implications for public health practice? RZV is the first herpes zoster vaccine approved for use in immunocompromised persons. With moderate to high vaccine efficacy and an acceptable safety profile, RZV has the potential to prevent considerable herpes zoster incidence and related complications.

Nitazoxanide treatment for norovirus infection in solid organ transplant recipients - Hedvat, Jessica; Salerno, David M.; Kovac, Danielle; Scheffert, Jenna L.; Corbo, Heather; Chen, Justin K.; Choe, Jason Y.; Jennings, Douglas L.; Anamisis, Anastasia; Liu, Esther C.; Lee, Jennifer H.; Shertel, Tara; et al. (Clinical Transplantation, 2022)

Cytomegalovirus Donor Seropositivity Negatively Affects Survival After Heart Transplantation - Heim, Christian; Müller, Philipp P.; Tandler, René; Cherikh, Wida S.; Toll, Alice E.; Stehlik, Josef; Weyand, Michael; Khush, Kiran K.; Ensminger, Stephan M. (Transplantation, 2022)
Objectives: Prior studies have shown that cytomegalovirus(CMV) infection is a risk factor for the development of cardiac allograft vasculopathy(CAV) and is associated with reduced long-term survival after heart transplantation. The aim of this ISHLT Transplant Registry study was to compare post-transplant survival in different CMV donor:recipient serologic combinations. Methods: We performed a retrospective cohort study, using the ISHLT Thoracic Transplant Registry, on 15,885 adult primary heart transplant recipients with known CMV serologic status between 7/2004 and 6/2014. Post-transplant survival and risk of developing CAV were compared across 4 groups: CMV-seronegative recipients(R-) receiving CMV-positive grafts(D+), intermediate-risk patients(D+R+ and D-R+), and low-risk patients(D-R-). Results: Baseline characteristics (donor/recipient age, BMI, recipient serum creatinine, blood group, donor cause of death, recipient diagnosis and ischemic time) were mostly balanced between the groups. Kaplan Meier survival analyses over a follow up of 10 years revealed significantly worse survival for both D+ groups as compared to the CMV low risk group (D+R+:56.61% (95%CI 53.94,59.41) vs. D-R-:63.09% (59.74,66.64) p<.01 and D+R-:57.69% (56.03,59.39) vs. D-R-; p<.001), whereas recipient seropositivity alone was not associated with reduced survival (D-R+ vs. D-R- p=.178). The risk of developing CAV after HTx was not significantly increased in D+ as compared to D- groups. Conclusion: In a large contemporary cohort, CMV status at the time of heart transplantation was not associated with CAV development. However, there was a significant association between donor CMV seropositivity and reduced short- and long-term survival after heart transplantation. Approaches to mitigate the impact of CMV on post-transplant survival are needed. Supplemental Visual Abstract; https://links.lww.com/TP/C292

Novel antifungal agents in clinical trials - Jacobs, Samantha E.; Zagaliotis, Panagiotis; Walsh, Thomas J. (F1000Research, 2022)
Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics.  The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics.  This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim.  We discuss three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.
Keywords: Antifungal Agents; Drug Resistance, Fungal; Fungi; Immunocompromised Host; clinical trials; novel treatments; pharmacokinetic and pharmacodynamic

High False-Positive Rate of (1,3)-β-D-Glucan in Onco-Hematological Patients Receiving Immunoglobulins and Therapeutic Antibodies - Tschopp, Jonathan; Brunel, Anne-Sophie; Spertini, Olivier; Croxatto, Anthony; Lamoth, Frederic; Bochud, Pierre-Yves (Clinical Infectious Diseases, 2022)
Immunoglobulins and/or therapeutic antibody preparations are associated with a high rate of false-positive (1,3)-β-D-glucan (BDG) tests in onco-hematological patients routinely screened for fungal infections. The benefit of BDG monitoring shall be balanced against the risk of false-positive tests leading to unnecessary investigations and costs in this population.

Investigational antifungal agents for invasive mycoses: a clinical perspective - Lamoth, Frederic; Lewis, Russell E.; Kontoyiannis, Dimitrios P. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2022)
Treatment of invasive fungal infections (IFI) remains challenging, because of the limitations of the current antifungal agents (i.e. mode of administration, toxicity, drug-drug interactions), and the emergence of resistant fungal pathogens. Therefore, there is an urgent need to expand our antifungal armamentarium. Several compounds are reaching the stage of phase II or III clinical assessment. These include new drugs within the existing antifungal classes or displaying similar mechanism of activity with improved pharmacologic properties (rezafungin, ibrexafungerp) or first-in-class drugs with novel mechanisms of action (olorofim, fosmanogepix). Although critical information regarding the performance of these agents in heavily immunosuppressed patients is pending, they may provide useful additions to current therapies in some clinical scenarios, including IFI caused by azole-resistant Aspergillus or multi-resistant fungal pathogens (e.g. Candida auris, Lomentospora prolificans). However, their limited activity against Mucorales and some other opportunistic molds (e.g. some Fusarium spp.) persists as a major unmet need.
Keywords: APX001; CD101; E1211; F901318; SCY078; VT-1129; VT-1161; VT-1598

Impact of letermovir primary Cytomegalovirus (CMV) prophylaxis on 1-year mortality after allogeneic hematopoietic cell transplantation (HCT): a retrospective cohort study - Su, Yiqi; Stern, Anat; Karantoni, Eleni; Nawar, Tamara; Han, Gyuri; Zavras, Phaedon; Dumke, Henry; Cho, Christina; Tamari, Roni; Shaffer, Brian; Giralt, Sergio; Jakubowski, Ann; et al. (Clinical Infectious Diseases, 2022)
CMV seropositive (R+) hematopoietic cell transplant (HCT) recipients have a survival disparity compared with CMV seronegative recipient/donor (R-D-) pairs. We hypothesized that primary letermovir prophylaxis (LET) may abrogate this disparity. We investigated the relationship between LET and mortality at 1year post-HCT.In this retrospective cohort study, we included adult R-D- or R+ patients who received HCT pre-LET (between January 1, 2013 through December 15, 2017) and post-LET (between December 16, 2017 through December 2019). R+ were categorized by LET receipt as R+/LET or R+/no-LET. Cox proportional hazard models were used to estimate the association of LET with all-cause mortality at one-year post-transplantation.Of 848 patients analyzed, 305 were R-D-, 364 R+/no-LET and 160 R+/LET. Because of similar mortality (adjusted hazard ratio [aHR] [95% confidence interval]); 1.29 [0.76-2.18; p=0.353] between pre-LET/R-D- and post-LET/R-D-, R-D- were combined into one group. Compared with R-D-, the aHR for mortality was 1.40 [1.01-1.93] for R+/no-LET and 0.89 [0.57-1.41] for R+/LET. Among R+, LET was associated with decreased risk of death (aHR 0.62 [0.40-0.98]); when conventional and T-cell depleted HCT were analyzed separately, the aHR was 0.86 [0.51-1.43] and 0.21 [0.07-0.65] respectively.At one-year post HCT, LET was associated with closing the mortality disparity between R-D- and R+. Among all R+, LET was associated with decreased mortality; driven by 79% reduced incidence of death in T-cell depleted HCT.

Prevalence and Healthcare Burden of Fungal Infections in the United States, 2018 - Rayens, Emily; Norris, Karen A (Open Forum Infectious Diseases, 2022)
Background.  Fungal infections are responsible for >1.5 million deaths globally per year, primarily in those with compromised immune function. This is concerning as the number of immunocompromised patients, especially in those without human immunodeficiency virus (HIV), has risen in the past decade. The purpose of this analysis was to provide the current prevalence and impact of fungal disease in the United States. Methods.  We analyzed hospital discharge data from the most recent (2018) Healthcare Cost and Utilization Project National Inpatient Sample, and outpatient visit data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. Costs are presented in 2018 United States (US) dollars. Results.  In the 35.5 million inpatient visits documented in 2018 in the US, approximately 666 235 fungal infections were diagnosed, with an estimated attributable cost of $6.7 billion. Aspergillus, Pneumocystis, and Candida infections accounted for 76.3% of fungal infections diagnosed, and 81.1% of associated costs. Most fungal disease occurred in patients with elevated risk of infection. The visit costs, lengths of stay, and risks of mortality in this population were more than twice that of those without fungal diagnoses. A further 6.6 million fungal infections were diagnosed during outpatient visits. Conclusions.  Fungal disease is a serious clinical concern with substantial healthcare costs and significant increases in morbidity and mortality, particularly among predisposed patients. Increased surveillance, standardized treatment guidelines, and improvement in diagnostics and therapeutics are needed to support the rising numbers of at-risk patients.
Keywords: HCUP; Healthcare Cost and Utilization Project; NIS; National Inpatient Sample; fungal disease; mortality; mycoses

Resolution of Cryptosporidiosis in Transplant Recipients: Review of the Literature and Presentation of a Renal Transplant Patient Treated With Nitazoxanide, Azithromycin, and Rifaximin - Tomczak, Ewa; McDougal, April N; White, A Clinton (Open Forum Infectious Diseases, 2022)
Background.  Cryptosporidium is a major cause of diarrheal disease worldwide, including chronic disease in malnourished children and patients with acquired immune deficiency syndrome. There are increasing reports of cryptosporidiosis in transplant patients, especially from middle-income countries. Methods.  The literature on treatment of cryptosporidiosis in transplant patients was reviewed and included no controlled trials but only small case series. Nitazoxanide, azithromycin, spiramycin, and combination therapies have been used, but none are consistently efficacious. Results.  We present a case of chronic diarrhea from cryptosporidiosis in a renal transplant patient. His illness resolved with decreasing immunosuppression and treatment with the 3-drug combination of nitazoxanide, azithromycin, and rifaximin. Conclusions.  Although current therapies are not reliably effective in the absence of an effective cellular immune response, combination therapies hold promise for improved responses.

An Open-label Randomized Controlled Parallel-group Pilot Study Comparing the Immunogenicity of a Standard-, Double-, and Booster-dose Regimens of the 2014 Seasonal Trivalent Inactivated Influenza Vaccine in Kidney Transplant Recipients - Odongo, Fatuma Catherine Atieno; Braga, Patrícia Emília; Palacios, Ricardo; Miraglia, João Luiz; Sartori, Ana Marli Christovam; Ibrahim, Karim Yaqub; Lopes, Marta Heloisa; Caiaffa-Filho, Helio Hehl; Timenetsky, Maria do Carmo Sampaio Tavares; Agena, Fabiana; Fonseca de Azevedo, Luiz Sergio; David-Neto, Elias; et al. (Transplantation, 2022)
Background. Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. Methods. We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV), and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59), and BDTIIV regimens (58). Antibody titers were determined by hemagglutination inhibition at enrollment and 21 d postvaccination. Seroprotection rates (SPRs), seroconversion rates (SCRs), and geometric mean ratios (GMRs) were analyzed separately for participants with low (<1:40) and high (≥1:40) prevaccination antibody titers. Results. Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided postvaccination blood samples. In the subgroup with high prevaccination antibody titers, all vaccination regimens induced SPR > 70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low prevaccination antibody titers, DDTIIV and BDTIIV regimens induced adequate SCR > 40% and GMR > 2.5 for all antigens, whereas SDTIIV achieved the same outcomes only for influenza B. SPRs were >70% only after DDTIIV (A/H1N1—77.8%) and BDTIIV (A/H3N2—77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR = 2.58; P = 0.021) and A/H3N2 (PR = 2.21; P = 0.004), whereas DDTIIV independently increased seroprotection to A/H1N1 (PR = 2.59; P = 0.021). Conclusions. Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients - van den Bogaart, Lorena; Lang, Brian M.; Neofytos, Dionysios; Egli, Adrian; Walti, Laura N.; Boggian, Katia; Garzoni, Christian; Berger, Christoph; Pascual, Manuel; van Delden, Christian; Mueller, Nicolas J.; Manuel, Oriol; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2022)
Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations.
Keywords: Bacterial Infections; Humans; Incidence; Organ Transplantation; Prospective Studies; Transplant Recipients; clinical research/practice; complication: infectious; epidemiology; infection and infectious agents - bacterial; infectious disease; patient safety

A comprehensive review of Strongyloides stercoralis infection after solid organ and hematopoietic stem cell transplantation - Abad, Cybele Lara R.; Bhaimia, Eric; Schuetz, Audrey N.; Razonable, Raymund R. (Clinical Transplantation, 2022)
Background: We reviewed the scientific literature to gain insight on the epidemiology and outcome of Strongyloides stercoralis infections after transplantation. Methods: CINAHL, PUBMED, and OVID/MEDLINE were reviewed from inception through March 31, 2022 using key words Strongyloides and transplantation. Results: Our review identified 108 episodes of Strongyloides infection among 91 solid organ transplant (SOT) and 15 hematopoietic cell transplant (HCT) recipients. Median time to infection was 10.8 (range, .14–417) and 8.8 (range, 0–208) weeks after SOT and HCT, respectively. Gastrointestinal symptoms were frequent (86/108 [79.6%]), while skin rash (22/108 [20.3%]) and fever (31/103 [30%]) were less common. Peripheral eosinophilia was observed in half of patients (41/77 [53.2%]). Bacteremia (31/59 [52.5%]) was frequently due to Gram-negative organisms (24/31 [77.4%]). Abnormal chest radiologic findings were reported in half (56/108 [51.9%]). The majority had hyperinfection syndrome (97/108 [89.8%]) while disseminated strongyloidiasis was less common (11/108 [10.2%]). Thirty-two cases were categorized as donorderived infection (DDI), with donors (23/24 [95.8%]) who had traveled to or lived in endemic areas. Median time to DDI was 8 weeks (range .5–34.3 weeks) after transplantation. Treatment consisted of ivermectin (n = 26), a benzimidazole (n = 27), or both drugs (n = 28). There was high all-cause mortality (48/107, 44.9%) and a high Strongyloides-attributable mortality (32/49, 65.3%). Conclusions: Strongyloidiasis should be strongly considered among recipients with epidemiologic risk factors for infection, even in the absence of eosinophilia or rash. A policy that provides guidance on pro-active screening is needed, to ensure preventive measures are provided to recipients at increased risk.
Keywords: Strongyloides; hematopoietic stem cell transplant; hyperinfection syndrome; ivermectin; solid organ transplant; strongyloidiasis

Tyrosine-Kinase Inhibitors - Abad, Cybele Lara R.; Razonable, Raymund R. (Infectious Complications in Biologic and Targeted Therapies, 2022)
Tyrosine kinases inhibitors (TKIs) are small molecules that have been developed as targeted therapies for various medical conditions. They act specifically on tyrosine kinases, a family of membrane-bound or intracellular molecules that regulate a variety of important cellular functions. TKIs have emerged as treatment for hematologic malignancies and autoimmune diseases. Each class of TKI has unique features and often acts on a specific receptor, minimizing the risk of adverse effects and infectious sequelae. Despite this targeted therapy, however, infectious complications have emerged as a major obstacle for many of these agents. Depending on the specific class of TKI, there is often an increased risk of neutropenia, or a higher risk for pneumonia and other respiratory infections. Reactivation of latent infections and opportunistic infections may also occur. Screening for latent infections prior to initiation of therapy and prophylaxis should be considered depending on the TKI agents used.
Keywords: Herpes zoster; Infection risk; Pneumonia; Tyrosine kinase; Tyrosine kinase inhibitor

Cell-Surface Receptors: EGFR- and VEGFR-Targeted Agents - Aguilar-Company, Juan; Ruiz-Camps, Isabel (Infectious Complications in Biologic and Targeted Therapies, 2022)
This review aims to analyze, from an infectious disease perspective, the safety profile of antineoplastic therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest recommendations.
Keywords: Bevacizumab; Cetuximab; Panitumumab; Ramucirumab; Sorafenib; Sunitinib

Interleukin-1 Targeted Agents - Alam, Mosaab; Mah, Allison; Belga, Sara (Infectious Complications in Biologic and Targeted Therapies, 2022)
Introduction and Aims: Inhibition of the IL-1 pathway has been the target of treatments for several inflammatory conditions. This clinical review aims to summarize the risk of infectious complications associated with the use of interleukin-1 (IL-1) targeted therapy.
Keywords: Anakinra; Autoimmune; Biologics; Canakinumab; Gevokizumab; Infection; Interleukin-1; Monoclonal antibody; Rilonacept

Impact of narrowing perioperative antibiotic prophylaxis for left ventricular assist device implantation - Allen, Lauren; Bartash, Rachel; Minamoto, Grace Y.; Cowman, Kelsie; Patel, Snehal; Vukelic, Sasa; Nnani, Daryl U.; Fauvel, Daphenie; Guo, Yi (Transplant Infectious Disease, 2022)
Background: Although infections are a significant potential complication among patients undergoing left ventricular assist device (LVAD) implantation, standardized surgical infection prophylaxis (SIP) regimens are not well defined. At Montefiore Medical Center, a 4-drug SIP regimen containing fluconazole, ciprofloxacin, rifampin, and vancomycin was previously utilized. In January 2020, the antimicrobial stewardship program implemented a 2-drug SIP regimen of vancomycin and cefazolin to limit exposure to broad-spectrum antibiotics. This study evaluated LVAD-associated infection rates prior to and following the SIP revision. Methods: A retrospective review of patients who underwent LVAD implantation from 1/2018 to 4/2021 was performed. Infections were classified using the International Society for Heart and Lung Transplantation definitions. Infection rates at 2 weeks, 30 days, and 90 days post-implantation in the 4-drug SIP regimen (1/2018-12/2019) and the 2-drug SIP regimen (1/2020 to 4/2021) were compared. Results: A total of 71 patients were included. The number of patients with LVADassociated infections (including surgical site infections) was not significantly different in either SIP group at 2 weeks (9% vs. 4%, p = .64), 30 days (9% vs. 11%, p = .99), or 90 days (19% vs. 14%, p = .75). There was no statistically significant difference in 30 or 90-day mortality. LVAD-associated gram-negative (7% vs. 7%; p > .99) and fungal (5% vs. 0%; p = .51) infections were uncommon. The most common organism isolated was Staphylococcus aureus, and the most common type of infection was pneumonia in both SIP groups. Conclusion: No significant difference in LVAD-associated infections or infectionrelated mortality was observed with de-escalation of perioperative antibiotics. Additional studies with larger sample sizes are needed to endorse the findings of this study.
Keywords: Antimicrobial stewardship; LVAD-associated infections; device infection; left ventricular assist devices; surgical infection prophylaxis; surgical site infections

Current state of antimicrobial stewardship and organ transplantation in Saudi Arabia - Almaziad, Sultan; Bosaeed, Mohammad (Transplant Infectious Disease, 2022)
Background Antimicrobial resistance constitutes a major public health issue that leads to poor outcomes and increased costs associated with healthcare. Solid organ transplant recipients are more prone due to prolonged exposure to antimicrobials. Methods We reviewed existing programs in the Kingdom of Saudi Arabia and pattern of drug resistance, and the extent of transplant medicine in the kingdom through published articles in databases and official documents from health authorities. Results A national committee for antimicrobial resistance (AMR) was established to set the guidelines required for an antimicrobial stewardship program (ASP), especially when there is a high prevalence of AMR. A survey noted that ASPs are implemented in only 26% of Saudi Ministry of Health hospitals. Factors affecting the implementation of ASPs in Saudi hospitals included a lack of necessary staff resources and specific ASP staff/teams to advocate adopting ASP in the organizations. Specific attention should be given to transplant patients as transplantations are expected to increase in the next few years. No antimicrobial stewardship programs are currently specifically tailored to transplant centers. Conclusion The current healthcare system transformation in Saudi Arabia should take into consideration the urgent need for effective ASP that might help face the increasing trends in the multidrug-resistant organisms (MDRO) prevalence rate.
Keywords: ASP; Saudi Arabia; antimicrobial stewardship; organ transplant

Treatment of asymptomatic bacteriuria in the first 2 months after kidney transplant: A controlled clinical trial - Antonio, Mendoza Enciso Emmanuel; Cassandra, Barajas García Carolina; Emiliano, Rodriguez Jimenez Dante; Guadalupe, Ortiz Lopez Margarita; Lilian, Reza Escalera Ana; Teresa, Tiscareño Gutiérrez María; Mario, Gonzalez Gamez; Ivan, Rodríguez Correa Gustavo; Mercedes, Ramos Velazco; Alfredo, Chew Wong; Rafael, Reyes Acevedo; Lilian, Guerrero Barrera Alma; et al. (Transplant Infectious Disease, 2022)
Background The incidence of urinary tract infections (UTIs) in the first 2 months postrenal transplantation (pRT) is very high. We evaluate the efficacy of asymptomatic bacteriuria (AB) screening and treatment on the incidence of UTI in the first 2 months pRT Methods We conducted a randomized controlled clinical trial. A urine culture was obtained in all patients on the day of the bladder catheter removal, on week three, and before removal of the ureteral catheter. The intervention group received treatment for AB. The control group did not receive treatment. The primary outcomes were the cumulative incidence of UTI and/or graft pyelonephritis and the time to the first episode of UTI and/or graft pyelonephritis Results Eighty patients were randomized, 40 in each group, and the median follow-up was 63 days (IQR 54–70). The average age was 29.8 years and 33.7% (n = 27) were women. The incidences of UTI (n = 10, 25 % vs. n = 4, 10%, p = .07) and pyelonephritis (n = 6, 15% vs. n = 1, 2.5%, p = .04) were greater in the intervention group, as also shown in the survival analysis: UTI (HR2.8, 95% CI 0.8–9.1, p = .07) and pyelonephritis (HR 6.5, 95% CI 0.8–54.7, p = .08), respectively. The most commonly isolated bacterium was Escherichia coli (n = 28, 59.5%), and over half were E. coli with extended-spectrum beta-lactamases (n = 15). A major limitation was not obtaining the calculated sample size due to a delay in patient recruitment resulting from the COVID-19 pandemic Conclusion Treatment of AB in the first 2 months pRT does not decrease the incidence of UTI or graft pyelonephritis and may actually increase their frequency. Routine treatment of AB during the first months after renal transplantation should not be a standard procedure.
Keywords: asymptomatic bacteriuria; graft pyelonephritis; renal transplantation; urinary tract infection

Cytokine Release Syndrome and Sepsis - Athale, Janhavi; Busch, Lindsay M.; O’Grady, Naomi P. (Infectious Disease Clinics of North America, 2022)

Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge - Avery, Robin Kimiko (Transplantation, 2022)
Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12-18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.

Management of Cytokine Release Syndrome (CRS) and HLH - Ayuketang, Francis Ayuk; Jäger, Ulrich (The EBMT/EHA CAR-T Cell Handbook, 2022)
Cytokine release syndrome (CRS) is caused by a rapid and mild to massive release of cytokines from immune cells involved in immune reactions, particularly after immunotherapy. The frequency and severity of CRS after CAR-T cell therapy varies between products (any grade: 37–93%, G3/4: 1–23%) (Neelapu et al. 2017; Schuster et al. 2019; Abramson et al. 2020).

Management of Cytokine Release Syndrome (CRS) and HLH - Ayuketang, Francis Ayuk; Jäger, Ulrich (The EBMT/EHA CAR-T Cell Handbook, 2022)
Abstract Cytokine release syndrome (CRS) is caused by a rapid and mild to massive release of cytokines from immune cells involved in immune reactions, particularly after immunotherapy. The frequency and severity of CRS after CAR-T cell therapy varies between products (any grade: 37–93%, G3/4: 1–23%) (Neelapu et al. 2017; Schuster et al. 2019; Abramson et al. 2020).

Risk factors and outcomes of COVID associated mucormycosis in kidney transplant recipients - Bansal, Shyam B.; Rana, Abhyuday; Babras, Mayur; Yadav, Dinesh; Jha, Pranaw; Jain, Manish; Sethi, Sidharth K. (Transplant Infectious Disease, 2022)
Background Invasive mucormycosis (IM) is a life-threatening fungal infection occurring mostly in solid organ transplant (SOT) recipients, patients with hematological malignancies, and diabetes. A sudden spurt of mucormycosis has been reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in India; however, there is little data about coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) in kidney transplant recipients (KTRs). Methods We describe the clinical presentations, risk factors, treatment and outcomes of 11 mucormycosis cases in KTRs post-COVID-19 infection from February 2020 to June 2021 at a single center in India. Results Mucormycosis was seen in 11/102 (10.7%) KTRs during the pandemic. Six patients had mild disease and rest five had moderate disease. Seven patients had pre-existing diabetes mellitus and four developed new onset hyperglycemia after receiving steroids for COVID-19 infection. All had poorly controlled sugars at the time of presentation. Most common presentation was rhino-orbital-cerebral mucormycosis (ROCM) in 10/11 (89%) patients and one has pulmonary mucormycosis. All patients received combination of amphotericin B and surgical debridement/excision of affected tissue followed by posaconazole prophylaxis. Nine patients recovered, however two patients succumbed to their illness after median of 14 (7–21) days from diagnosis. One patient developed acute T-cell-mediated rejection during the course of recovery. At last follow up, the mean serum creatinine was 2.05 mg/dl as compared to 1.4 mg/dl at presentation. Conclusions IM is a common fungal infection in transplant recipients in India after COVID-19. Early diagnosis and prompt treatment with combination of surgical debridement and liposomal amphotericin B are key to better outcomes in CAM. Judicious use of steroids and control of hyperglycemia is key to avoid flaring up of the fungal infection.
Keywords: CAM; COVID-19 infection; invasive fungal infection; kidney transplant; mucormycosis

Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia - Bergeron, Anne; Mikulska, Malgorzata; De Greef, Julien; Bondeelle, Louise; Franquet, Tomas; Herrmann, Jean-Louis; Lange, Christoph; Spriet, Isabel; Akova, Murat; Donnelly, J Peter; Maertens, Johan; Maschmeyer, Georg; et al. (The Lancet Infectious Diseases, 2022)

Antimicrobial stewardship programs in solid-organ transplant recipients in Switzerland - Bielicki, Julia A.; Manuel, Oriol; Study (STCS), the Swiss Transplant Cohort (Transplant Infectious Disease, 2022)
Introduction Antimicrobial stewardship programs (ASPs) are essential for minimizing the emergence of antimicrobial resistance, while improving patient outcomes. The current status of ASP in the field of organ transplantation in Switzerland has not been well characterized. Methods We describe in this article the current status of ASP and discuss challenges and opportunities of implementing ASP dedicated to solid-organ transplant (SOT) recipients in Switzerland. Results ASP have been implemented in the Swiss healthcare system over the last years, although specific strategies for SOT recipients are mostly based on transplant infectious diseases (TID) consultations rather than structured institutional interventions. Even so, there is a unique opportunity for developing a successful ASP in Switzerland that also specifically addresses areas of practice relevant to SOT recipients. This is due to the existent network of TID specialists in close collaboration with transplant physicians, the small number of centers involved in the care of transplant recipients, and the development of the Swiss Transplant Cohort Study (STCS), a prospective nationwide cohort of SOT recipients in Switzerland. The STCS can identify actual challenges through the updated reports on the epidemiology on transplant infections, accurately monitor the impact of potential antimicrobial stewardship interventions, and represent an opportunity for nesting of pragmatic randomized controlled trials to address key questions about optimized antibiotic use for SOT recipients. Conclusions Although ASP in SOT recipients rely more on specific TID consultations than in general antimicrobial stewardship teams, we identified several opportunities for the implementation of a successful ASP in Switzerland.
Keywords: antibiotic use; antimicrobial stewardship; transplant infections

Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study - Blumberg, Emily A.; Collins, Gary; Young, Jo-Anne H.; Nguyen, M. Hong; Michonneau, David; Temesgen, Zelelem; Origȕen, Julia; Barcan, Laura; Obeid, Karam M.; Belloso, Waldo H.; Gras, Julien; Corbelli, Giulio Maria; et al. (Transplant Infectious Disease, 2022)
Background Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. Methods Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. Results A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6–133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01). Conclusions Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.
Keywords: Clostridium difficile infection; hematopoietic stem cell transplantation; solid organ transplantation

Dissemination and implementation science and antimicrobial stewardship in solid organ transplantation: A perspective - Burnham, Jason P.; Kwon, Jennie H.; Newland, Jason G.; McKay, Virginia R. (Transplant Infectious Disease, 2022)
Background Recipients of solid organ transplants (SOTs) have unique risks for infections, but providers are often hesitant to apply the principles of antimicrobial stewardship to this patient population due to perceived excess risk. The methods of implementation science may move the field forward to simultaneously improve patient outcomes and patient safety. Methods Perspective piece on implementation science in SOT patients. Results Herein, we provide explanation of implementation science as it relates to SOT patients. In addition, we provide examples of how implementation science can be applied to antimicrobial stewardship in SOT patients. Conclusion Implementation science may offer insights and solutions to the challenges of implementing evidence-based antimicrobial stewardship interventions in patients with SOT, including uptake of new practices and the de-implementation of outdated or low-value practices.
Keywords: antimicrobial stewardship; dissemination and implementation science; solid organ transplant

Voriconazole therapeutic drug monitoring among lung transplant recipients receiving targeted therapy for invasive aspergillosis - Butler-Laporte, Guillaume; Langevin, Marie-Claude; Lemieux, Claude; Poirier, Charles; Ferraro, Pasquale; Théorêt, Yves; Luong, Me-Linh (Clinical Transplantation, 2022)
Background Voriconazole is the first line treatment for invasive aspergillosis (IA) Current guidelines suggest performing regular voriconazole therapeutic drug monitoring (TDM) to optimize treatment efficacy. We aimed to determine if TDM was predictive of clinical outcome in LTRs. Methods Retrospective chart review was performed for all LTRs with probable or proven IA, treated with voriconazole monotherapy and who underwent TDM during therapy. Clinical outcome and toxicity were measured at 12 weeks. Classification and regression tree (CART) analysis was used to determine the most predictive voriconazole level thresholds for successful outcome. Results One hundred and eighteen TDM samples from 30 LTRs with IA were analyzed. Three LTRs were excluded due to early treatment discontinuation. The median TDM level was 1.2 μg/ml (range 0.06–7.3). At 12 weeks, 62% (17/27) of patients had a successful outcome, while 37% (10/27) of patients failed therapy. CART analysis determined that the best predictor for successful outcome was a median TDM level >0.72 μg/ml. Seventy percent (14/20) of patients with median TDM above 0.72 μg/ml had a successful outcome, compared to 42.9% (3/7) of patients with a median TDM below 0.72 μg/ml (OR 3.11; 95% CI: 0.53–20.4; P = 0.21). CART analysis determined that a TDM level greater than 2.13 μg/ml was predictive of hepatotoxicity. Conclusions Our data suggests that a voriconazole TDM range between 0.72 μg/ml and 2.13 μg/ml may be associated with improved outcomes. Our study is in line with current recommendations on the use of voriconazole TDM in improving outcome and minimizing toxicity in LTR with IA.
Keywords: fungal infection; invasive aspergillosis; lung transplant; therapeutic drug monitoring; voriconazole

Hyperammonemia syndrome post-lung transplantation: Case series and systematic review of literature - Buzo, Bruno Fernando; Preiksaitis, Jutta K.; Halloran, Kieran; Nagendran, Jayan; Townsend, Derek R.; Zelyas, Nathan; Sligl, Wendy I. (Transplant Infectious Disease, 2022)
Background Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant recipients and its pathophysiology is not well understood. In addition to underlying metabolic abnormalities, it is postulated that HS may be associated with Ureaplasma or Mycoplasma spp. lung infections. Management of this condition is not standardized and may include preemptive antimicrobials, renal replacement, nitrogen scavenging, and bowel decontamination therapies, as well as dietary modifications. Methods In this case series, we describe seven HS cases, five of whom had metabolic deficiencies ruled out. In addition, a literature review was performed by searching PubMed following PRISMA-P guidelines. Articles containing the terms “hyperammonemia” and “lung” were reviewed from 1 January 1997 to 31 October 2021. Results All HS cases described in our center had positive airway samples for Mycoplasmataceae, neurologic abnormalities and high ammonia levels post-transplant. Mortality in our group (57%) was similar to that published in previous cases. The literature review supported that HS is an early complication post-transplant, associated with Ureaplasma spp. and Mycoplasma hominis infections and of worse prognosis in patients presenting cerebral edema and seizures. Conclusion This review highlights the need for rapid testing for Ureaplasma spp. and M. hominis after lung transplant, as well as the necessity for future studies to explore potential therapies that may improve outcomes in these patients.
Keywords: Ureaplasma; hyperammonemia syndrome; lung transplant; mortality; outcomes

What is the optimal antimicrobial prophylaxis to prevent postoperative infectious complications after liver transplantation? A systematic review of the literature and expert panel recommendations - Campos-Varela, Isabel; Blumberg, Emily A.; Giorgio, Patricia; Kotton, Camille N.; Saliba, Fauzi; Wey, Emmanuel Q; Spiro, Michael; Raptis, Dimitri Aristotle; Villamil, Federico; Group, the ERAS4OLT org Working (Clinical Transplantation, 2022)
Background Antimicrobial prophylaxis is well-accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined. Objectives To identify the optimal antimicrobial prophylaxis to prevent post-LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short-term outcomes, and to provide international expert panel recommendations. Data sources Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Methods Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID: CRD42021244976. Results Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included. Conclusions Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong).
Keywords: antibiotic; antifungal; antimicrobial; antimycotic; hepatic; liver; prophylactic; prophylaxis; transplant; transplantation

Use of hepatitis B viremic donors in kidney transplant recipients: A single center experience - Carnemolla, Brooke T.; Kutzler, Heather L.; Kuzaro, Hillary A.; Morgan, Glyn; Serrano, Oscar K.; Ye, Xiaoyi; Cheema, Faiqa (Transplant Infectious Disease, 2022)
Utilization of Hepatitis B virus (HBV)-infected kidney allografts represents an opportunity to bridge the gap between organ supply and demand. Highly efficacious vaccines and antiviral therapies allow these allografts to be transplanted with negligible risk to the recipient. The purpose of this study was to describe the prophylactic strategies and related clinical outcomes of kidney transplant recipients who received a kidney from an HBV viremic donor. Eight patients received an allograft from an HBV viremic deceased kidney donor between January 1, 2017 and December 4, 2020. All recipients were immune to hepatitis B with a surface antibody titer greater than or equal to 10 mIU/ml (range: 12 - > 1000 mIU/ml). After transplant, 62.5% demonstrated HBV core antibody seroconversion at an average of 47.4 ± 28.5 days post-transplant. Anti-viral prophylaxis was initiated in 87.5% of patients; 62.5% preemptively during the transplant admission (range 1–3 days post-transplant) and 25% following HBcAb seroconversion (range 45–304 days post-transplant). Of the four patients who were started on entecavir preemptively, two subsequently core converted. These two patients had an HBV surface antibody less than 100 mIU/ml at the time of transplant. None of the recipients converted to HBV surface antigen positivity. The average estimated glomerular filtration rate was 41 ± 19 ml/min/1.73m2, and there were no significant elevations in liver enzymes through one year post-transplant. The use of HBV viremic kidney allografts may represent an additional source of transplant organs; however, more studies are needed to better elucidate the optimal protective strategies for these recipients.
Keywords: HBV; entecavir; hepatitis B; kidney transplant; solid organ transplant; transplant

Could cell-free DNA and host biomarkers assist in antimicrobial stewardship with organ transplant recipients? - Chang, Sandy Y.; Santos, Carlos A. Q. (Transplant Infectious Disease, 2022)
Background Antimicrobial stewardship in solid organ transplant (SOT) recipients is important to prevent antimicrobial-associated complications, but traditional stewardship principles are challenging to implement for SOT patients. Newer methodologies to optimize stewardship efforts are needed. Methods PubMed was searched using the keywords “cell free DNA,” “metagenomic sequencing,” “host biomarker,” “antimicrobial stewardship,” and “SOT.” Results Metagenomic sequencing of cell free DNA has the potential to be a stewardship tool for SOT recipients. Various studies have shown its use for antimicrobial de-escalation and duration shortening. Host gene expression profiles can differentiate between infectious and noninfectious syndromes and may assist in stewardship efforts. However, information in immunocompromised hosts is conflicting. Conclusion Microbial cell free DNA sequencing and host gene expression profiling show promise as stewardship tools in SOT recipients. Future studies on antimicrobial stewardship in SOT recipients should focus on their clinical use and feasibility.
Keywords: antimicrobial stewardship; cell-free DNA; gene expression profiling; solid organ transplant

Vaccination in pediatric solid organ transplant: A primer for the immunizing clinician - Chen, Justin K.; Cheng, Jennifer; Liverman, Rochelle; Serluco, Anastacia; Corbo, Heather; Yildirim, Inci (Clinical Transplantation, 2022)
Pediatric solid organ transplant (SOT) recipients are at a uniquely elevated risk for vaccine preventable illness (VPI) secondary to a multitude of factors including incomplete immunization at the time of transplant, inadequate response to vaccines with immunosuppression, waning antibody titers observed post-SOT, and uncertainty among providers on the correct immunization schedule to utilize post-SOT. Multiple guidelines are in existence from the Infectious Diseases Society of America and the American Society of Transplantation, which require use in adjunct with additional published references. We summarize the present state of SOT vaccine recommendations from relevant resources in tandem with the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidance utilizing both routine and rapid catch-up schedules. The purpose of this all-inclusive review is to provide improved clarity on the most optimal pre- and post-transplant vaccine management within a one-stop-shop for the immunizing clinician.
Keywords: immunizations; immunosuppression; pediatric; solid organ transplant; vaccine

Infectious complications in acute graft‐versus‐host disease after liver transplantation - Chesdachai, Supavit; Udompap, Prowpanga; Yetmar, Zachary A.; Watt, Kymberly D.; Aqel, Bashar A.; Yang, Liu; Beam, Elena (Transplant Infectious Disease, 2022)

Association between gut colonization of vancomycin-resistant enterococci and liver transplant outcomes - Chiang, Diana; Dingle, Tanis C.; Belga, Sara; Kabbani, Dima; Bhanji, Rahima A.; Walter, Jens; Abraldes, Juan G.; Cervera, Carlos (Transplant Infectious Disease, 2022)
Background Vancomycin-resistant enterococci (VRE) colonization is common in liver transplant recipients and has been associated with worse posttransplant outcomes. Methods We conducted a retrospective cohort study at the University of Alberta Hospital including patients who underwent a liver transplant between September 2014 and December 2017. Results Of 343 patients, 68 (19.8%) had pretransplant VRE colonization and 27 (27/275, 9.8%) acquired VRE posttransplant, 67% were males and the median age was 56.5 years. VRE colonized patients at baseline had higher MELD scores and required longer posttransplant hospitalization. VRE colonization was associated with increased risk of early acute kidney injury (AKI) (64% vs. 52%, p = .044), clinically significant bacterial/fungal infection (29% vs. 17%, p = .012) and invasive VRE infection (5% vs. 1%, p = .017). Mortality at 2 years was 13% in VRE-colonized versus 7% in noncolonized (p = .085). On multivariate analysis, VRE colonization increased the risk of posttransplant AKI (HR 1.504, 95% CI: 1.077-2.100, p = .017) and clinically significant bacterial or fungal infection at 6 months (HR 2.038, 95% CI: 1.222–3.399, p = .006), and was associated with nonsignificant trend toward increased risk of mortality at 2 years posttransplant (HR 1.974 95% CI 0.890–4.378; p = .094). Conclusions VRE colonization in liver transplant patients is associated with increased risk of early AKI, clinically significant infections, and a trend toward increased mortality at 2 years.
Keywords: MELD; VRE colonization; acute kidney injury; liver transplantation; microbiota; mortality; posttransplant outcomes; vancomycin-resistant enterococci

Current state of antimicrobial stewardship and organ transplantation in Thailand - Chotiprasitsakul, Darunee; Bruminhent, Jackrapong; Watcharananan, Siriorn P. (Transplant Infectious Disease, 2022)
Background Antimicrobial stewardship (AMS) is a coherent set of actions to optimize antimicrobial use, improve patient outcomes, and reduce antimicrobial resistance (AMR). Thailand's national strategic plan has included AMS since 2017. Due to an increased risk of infection and AMR, solid organ transplant (SOT) recipients can benefit from antimicrobial stewardship programs (ASPs). However, the AMS in SOT has not been well defined. Balancing ASPs with the need for early and frequent antimicrobial treatment in this population is challenging. This review assesses the barriers and potential strategies of AMS in SOT in the setting of Thailand. Methods We used PubMed to identify published articles on AMS in organ transplantation in Thailand from January 2013 to January 2022. We also searched local literature and local data from Google Scholar and Google. Finally, we described the AMS experience at Ramathibodi hospital as a proxy for transplant centers in Thailand. Results There was no specific article on AMS in SOT in Thailand. At our hospital, ASPs have been part of the hospital's routine patient care, including the practice in the transplant unit. Modifiable challenges to AMS in SOT include prescriber opposition, diagnosis uncertainty, and lack of high quality. Both systems and individualized approaches should be implemented to overcome these barriers. The potential interventions include shortening antibiotic time-out, updating clinical guidelines, continuing education, handshake ASP, adopting new technology, and further research. Conclusions There are limited data on AMS in organ transplantation in Thailand. Strategic priorities should focus on modifiable barriers tailored to organ transplantation. Quality improvement should be ensured by process and outcome measures.
Keywords: antimicrobial resistance; antimicrobial stewardship; kidney transplantation; multidrug-resistant bacteria; solid organ transplantation

Anti-tumor Necrosis Factor-Alpha Agents - Chua, Joel V.; Baddley, John W. (Infectious Complications in Biologic and Targeted Therapies, 2022)
Tumor necrosis factor-α (TNF-α) plays a central role in the immunopathogenesis of a wide variety of inflammatory conditions from diseases such as rheumatoid arthritis to inflammatory bowel diseases. Development of TNF-α inhibitors (TNFI) has revolutionized the ability to treat these conditions, resulting in substantial improvement in clinical outcomes. Since the introduction of infliximab and etanercept in 1998, indications for the use of TNFI have expanded, and these medications are predominately prescribed by rheumatologists, dermatologists, and gastroenterologists for moderate to severe inflammatory and autoimmune diseases. As a result of widespread use of these effective therapies, there have been safety concerns related to immunosuppression, the foremost of which is the increased incidence of infections caused by a broad range of pathogens. In this chapter, we review available data on the epidemiology of infectious complications in patients receiving TNFI for the treatment of inflammatory conditions.
Keywords: Anti-TNF-α infections; Anti-tumor necrosis factor-alpha; Herpes zoster; Infection; Tuberculosis; Tumor necrosis factor-alpha

Current state of antimicrobial stewardship in organ transplantation in Singapore - Chung, Shimin Jasmine; Liew, Yixin; Lee, Winnie Hui Ling; Kwa, Andrea Lay Hoon; Tan, Thuan Tong; Tan, Ban Hock (Transplant Infectious Disease, 2022)
Background Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non-organ transplant patients (improved use of broad-spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients. Methods We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program. Results Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug-resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, “handshake stewardship”, is more appropriate. Conclusion To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy-in is key; empowering transplant physicians to be stewardship-focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi-disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.
Keywords: antimicrobial stewardship; handshake stewardship; hematopoietic stem cell transplantation; organ transplantation; solid organ transplantation

Delayed diagnosis and treatment of secondary syphilis in pancreas–kidney transplant recipient: Need for increased awareness of sexually transmitted infections in solid organ transplantation - Crossman, Hayley; Guterman, Elan; Fung, Monica (Transplant Infectious Disease, 2022)

Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial - de Jonge, Nick A; Sikkens, Jonne J; Zweegman, Sonja; Beeker, Aart; Ypma, Paula; Herbers, Alexandra H; Vasmel, Wies; de Kreuk, Arne; Coenen, Juleon L L M; Lissenberg-Witte, Birgit; Kramer, Mark H H; van Agtmael, Michiel A; et al. (The Lancet Haematology, 2022)

Utility of microbiologic testing in surveillance bronchoscopy following lung transplantation: A retrospective cohort study - Dillon, William P.; Acosta, Tommy Parraga; Failla, Andrew; Corrales, Julio; Alangaden, George; Ramesh, Mayur (Transplant Infectious Disease, 2022)
Background The utility of surveillance bronchoscopy (SB) for the clinical management of lung transplant recipients (LTRs) is undefined. This study evaluates the role of SB in the monitoring and care of LTRs. Methods We retrospectively analyzed all LTRs who had SB at Henry Ford Hospital in Detroit, Michigan between August 2014 and August 2019. Bronchoscopies performed for clinical symptoms, new radiographic abnormalities, and to assess stents or acute rejection were excluded. A total of 107 LTRs and 449 bronchoscopies were analyzed. The primary outcome was the rate of change in clinical care based on microbiologic and pathologic test results. Secondary outcomes were rates of microbiologic and pathologic test positivity and rates of adverse effects. Results The most common microbiologic tests performed on bronchoalveolar lavage were bacterial (96.9%), fungal (95.3%), and acid-fast bacillus (95.1%) stains and cultures. Of 2560 microbiologic tests, 22.0% were positive and resulted in therapy changes for 2.9%. Positive galactomannan, acid-fast bacillus tests, and Pneumocystis jirovecii antigen/polymerase chain reaction did not result in therapy changes. Of the 370 transbronchial biopsies performed, 82.2% were negative for acute rejection and 13% were positive for A1/A2 rejection. Immunosuppressive therapy changes occurred after 15.8% with reduction in immunosuppression due to positive microbiologic tests in 16.9%. Adverse events occurred in 8.0% of patients. Conclusion Diagnostic stewardship is warranted when performing SB in LTRs.
Keywords: antimicrobial stewardship; immunosuppression; lung transplants; rejection; surveillance bronchoscopy

Desirability of outcome ranking and quality life measurement for antimicrobial research in organ transplantation - Doernberg, Sarah B.; Group, MAS for the Antibacterial Resistance Leadership (Transplant Infectious Disease, 2022)
Background Current clinical trials of new antibiotics facilitate bringing new drugs to market but often fail to provide useful information for clinical decision making. Methods Literature review of desirability of outcome ranking (DOOR) in antibiotic clinical trials and description how DOOR can fit into design, administration, and assessment of clinical trials. Results DOOR is an approach that addresses many of the shortcomings of current trials by incorporating efficacy and safety into a single outcome to analyze the patient experience in its entirety. Application of partial credit, tiebreaker strategies including response adjusted for duration of antibiotic risk (RADAR), and DOOR for Management of Antimicrobial Therapy (DOOR MAT) provides additional nuance and granularity. To address pitfalls of DOOR, investigators must develop the DOOR a priori, ideally with input from and incorporation of patient voices, and should perform component analysis to ensure that imbalances in key components are detected. Conclusion Inclusion of DOOR in clinical trials will enrich our understanding of how new antibiotics might benefit patients who have had transplantation. Additional work to develop best practices for DOOR selection, analysis, and interpretation must continue, and incorporation of the patient perspective is essential.
Keywords: antibiotic-resistant bacteria; clinical trial design; desirability of outcome ranking; health-related quality of life

CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 - Drgona, Lubos; Masarova, Lucia (Infectious Complications in Biologic and Targeted Therapies, 2022)
This chapter is focused on the agents targeting lymphoid and myeloid cell surface antigens CD22, CD30, CD33, CD38, CD40, SLAMF-7 (CD319), and CCR-4. Over the past 20 years, many monoclonal antibodies targeting these antigens have been developed and introduced into clinical practice. Many of them are used successfully for the treatment of leukemia, lymphoma, multiple myeloma, and systemic autoimmune diseases (e.g. systemic lupus erythematosus, Sjogren’s syndrome) both in monotherapy and in combination with other drugs. Targeting these antigens, which are normally also present on immune system cells, is always concerning for the increased risk of infections in patients who are already immunocompromised due to hematologic malignancies. Furthermore, a longer follow-up would be needed to determine the real risk of some rare infections. This chapter evaluates the incidence, risk factors, and proposed prevention for infectious complications related to these drugs.
Keywords: Brentuximab vedotin; Daratumumab; Elotuzumab; Gemtuzumab ozogamicin; Infection; Inotuzumab ozogamicin; Mogamulizumab; Moxetumomab pasudotox

Management of Other Toxicities - Einsele, Hermann; Yakoub-Agha, Ibrahim (The EBMT/EHA CAR-T Cell Handbook, 2022)
Secondary haemophagocytic lymphohistiocytosis (sHLH) or macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur in patients with severe infections, e.g., COVID-19 infection, malignancy or autoimmune diseases. It is also a rare complication of allogeneic haematopoietic cell transplantation (allo-HCT), independent of the underlying trigger mechanism or underlying disorders associated with high mortality. There have been increasing reports of sHLH/MAS occurrence following CAR-T cell therapy, but its differentiation from cytokine release syndrome (CRS) is often difficult (Sandler et al. 2020).

Antimicrobial stewardship in solid organ transplantation: Perspective from a Veterans Affairs Medical Center - Felkner, Rebecca; Barnett, Susanne G.; Misch, Elizabeth A.; Safdar, Nasia; Balasubramanian, Prakash (Transplant Infectious Disease, 2022)
Background The importance of antimicrobial stewardship (AMS) activities specifically focused on solid organ transplant (SOT) recipients is increasingly recognized. In 2014, the Veterans Health Administration (VHA) created national guidance and committed resources to establish AMS programs at Veterans Affairs (VA) medical centers across the country. However, the AMS implementation is at the discretion of individual VA centers. Methods We undertook an environmental scan of AMS activities in a tertiary care VA medical center. Results We describe AMS activities focused on SOT recipients. Strategies based on local epidemiology that leverage the electronic medical record together with engagement by transplant infectious diseases personnel are likely to be beneficial. Conclusion AMS in SOT recipients is challenging yet impactful. Strategies described here may be useful for AMS activities focused on the SOT population.
Keywords: antimicrobial stewardship; organ transplant

Interleukin-12 and -23 Targeted Agents - Fernández-Ruiz, Mario (Infectious Complications in Biologic and Targeted Therapies, 2022)
The role of the structurally related interleukin-(IL) 12 and IL-23, as key drivers of Th1 and Th17 differentiation, in the pathogenesis of inflammatory chronic conditions has led to the development of various monoclonal antibodies targeted either at the common p40 subunit shared both cytokines (ustekinumab) or at the IL-23-specific p19 subunit (guselkumab, tildrakizumab, and risankizumab). These IL-12/23-targeted agents are currently approved for the treatment of plaque psoriasis, psoriatic arthritis, and inflammatory bowel disease in patients with inadequate response or intolerance to conventional or antitumor necrosis factor (TNF)-α therapies. Pivotal trials from the clinical development programs and post-marketing observational studies have shown an overall favorable safety profile in terms of infectious complications, with rates comparable to control groups. Although IL-12 and IL-23 blockade entails a theoretical risk of tuberculosis (TB) and superficial candidiasis, respectively, available clinical evidence suggests that the incidence of such events is actually lower compared to anti-TNF-α or anti-IL-17 agents. Pretreatment screening for latent TB infection and viral hepatitis, however, remains mandatory.
Keywords: Briakinumab; Guselkumab; Inflammatory bowel disease; Interleukin-12; Interleukin-23; Psoriasis; Risankizumab; Secukinumab; Tildrakizumab; Ustekinumab

Comparison of short-course antibiotic therapy of 6 or less days with a longer treatment in patients with cholangitis after liver transplantation - Ferstl, Philip G.; Queck, Alexander; Bremer, Katharina; Filmann, Natalie; Weiler, Nina; Welker, Martin-W.; Waidmann, Oliver; Knabe, Mate; Bechstein, Wolf O.; Hogardt, Michael; Kempf, Volkhard A. J.; Zeuzem, Stefan; et al. (Transplant Infectious Disease, 2022)
Objectives Stenosis of the biliary anastomosis predisposes liver graft recipients to bacterial cholangitis. Antibiotic therapy (AT) is performed according to individual clinical judgment, but duration of AT remains unclear. Methods All liver graft recipients with acute cholangitis according to the Tokyo criteria grade 1 and 2 after endoscopic retrograde cholangiography (ERC) were included. Outcome of patients treated with short AT (<7 days) was compared to long AT (>6 days). Recurrent cholangitis (RC) within 28 days was the primary end point. Results In total, 30 patients were included with a median of 313 (range 34–9849) days after liver transplantation until first proven cholangitis. Among 62 cases in total, 51/62 (82%) were graded as Tokyo-1 and 11/62 (18%) as Tokyo-2. Overall median duration of AT was 6 days (1–14) with 36 cases (58%) receiving short AT and 26 (42%) receiving long AT. RC was observed in 10 (16%) cases, without significant difference in occurrence of RC in short versus long AT cases. CRP and bilirubin were significantly higher in patients with long AT, while low serum albumin and low platelets were associated with risk of RC. Conclusion A shorter antibiotic course than 7 days shows good results in selected, ERC-treated patients for post-transplantation biliary strictures.
Keywords: biliary stricture; liver transplantation; multidrug resistance; recurrent cholangitis; short-course antibiotic therapy

Antimicrobial stewardship in solid organ transplantation—A call for action! - Forrest, Graeme N.; So, Miranda; Hand, Jonathan; Pouch, Stephanie; Husain, Shahid (Transplant Infectious Disease, 2022)

Challenges in implementing antimicrobial stewardship (AMS) in organ transplant centers in India - Ghafur, Abdul; Bansal, Nitin (Transplant Infectious Disease, 2022)
Introduction We, in India, have unique challenges in implementing antimicrobial stewardship (AMS) in our institutions, especially the transplant settings. Identifying challenges, addressing them, and finding innovative solutions to these are the need of the hour. Challenges Several challenges in India exists, which hamper implementation of effective AMS like lack of adequately trained personnel (infectious diseases [ID] physicians and clinical pharmacists), missing opportunities of AMS during the timeline, and lack of India-specific outcome measures for AMS programme. Solutions Finding local solutions can make our AMS implementation more effective. Numbers of ID physicians are increasing (24 in 2011 to >300 in 2020), and we expect the specialty to grow more and make rapid progress in AMS. We propose that cost savings and overall improvement in clinical outcome to be included in outcomes measures, rather than rates of C. difficle infection. Effective implementations of National Medical Commission mandatory AMS training regulation are few such steps that can fill the gaps. Conclusion Antimicrobial stewardship programs is one of the several components of tackling the antimicrobial resistance-related negative consequences in transplant patients. Transplant physicians, surgeons, and institutions should understand the bigger picture and strive hard to convince the policymakers to act for the benefit of the transplant recipients and the transplant programs across the country.
Keywords: Chennai Declaration; antimicrobial stewardship; transplant infectious diseases

Isoniazid prophylaxis in liver transplant recipient with latent tuberculosis: Is it harmful for transplanted liver? - Ghayumi, Seiyed Mohammad Ali; Shamsaeefar, Alireza; Motazedian, Nasrin; Mashhadiagha, Amirali; Sayadi, Mehrab; Nikeghbalian, Saman; Malekhosseini, Seyed Ali (Transplant Infectious Disease, 2022)

Letermovir for cytomegalovirus prophylaxis in high-risk heart transplant recipients - Golob, Stephanie; Batra, Jaya; DeFilippis, Ersilia M.; Uriel, Matan; Carey, Matt; Gaine, Maureen; Mabasa, Angelo; Fried, Justin; Raikelkar, Jayant; Restaino, Susan; Hi Lee, Sun; Latif, Farhana; et al. (Clinical Transplantation, 2022)
Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2–8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.
Keywords: CMV; heart transplant; letermovir

Perioperative antibiotic stewardship in the organ transplant setting - Graziano, Elena; Peghin, Maddalena; Grossi, Paolo Antonio (Transplant Infectious Disease, 2022)
Background Solid organ transplant (SOT) recipients can benefit from traditional antimicrobial stewardship (AMS) activities directed to improve judicious perioperative prescribing and management, but evidence is lacking. The aim of this expert opinion review is to provide an update on the current landscape of application of AMS practices for optimization of perioperative prophylaxis (PP). Methods We reviewed the available literature on early postoperative infectious complications in SOT and PP management, on modified perioperative approaches in case of infection or colonization in recipients and donors and on AMS in transplantation PP. Results SOT recipients are at high risk for early postoperative infectious complications due to the complexity of surgical procedures, severity of end stage organ disease, net state of immunosuppression in the posttransplant period and to the high risk for multidrug resistant organism. Moreover, SOT may be exposed to preservation fluid infections and expected or unexpected donor-derived infections. We summarize main factors to take into account when prescribing transplant PP. Conclusion Creating personalized PP to avoid unwanted consequences of antimicrobials while improving outcomes is an emerging and critical aspect in SOT setting. Further studies are needed to offer best PP tailored to SOT type and to evaluate interventions efficacy and safety.
Keywords: MDR; SOT; antimicrobial stewardship; donor derived infections; perioperative prophylaxis; preservation fluid

Solid Organ Transplantation From Deceased Donors With Infective Endocarditis: The UK Experience - Greenhall, George H. B.; Robb, Matthew L.; Brown, Chloe; Johnson, Rachel J.; Tomlinson, Laurie A.; Callaghan, Chris J.; Watson, Christopher J. E. (Transplantation, 2022)

An initiative to increase organ donor registration among persons with HIV - Haidar, Ghady; Bhamidipati, Divya; Despines, Linda; Sullivan, Colleen; Stuart, Susan; Beckham, J. Michael; McMahon, Deborah K.; Veldkamp, Peter (American Journal of Transplantation, 2022)