Antifungal resistance, combinations and pipeline: oh my! - Stover, Kayla R; Hawkins, Brandon K; Keck, J Myles; Barber, Katie E; Cretella, David A (Drugs in Context, 2023)
Invasive fungal infections are a strong contributor to healthcare costs, morbidity and mortality, especially amongst hospitalized patients. Historically, Candida was responsible for approximately 15% of all nosocomial bloodstream infections. In the past 10 years, the epidemiology of Candida species has altered, with increasing prevalence of resistant species. With rising fungal resistance, especially in Candida spp., the demand for novel antifungal therapies has exponentially increased over the last decade. Newer antifungal agents have become an attractive option for patients needing long-term therapy for infections or those requiring antifungal prophylaxis. Despite advances in coverage of non-Candida pathogens with newer agents, clinical scenarios involving multidrug-resistant fungal pathogens continue to arise in practice. Combination antifungal therapy can lead to a host of side-effects, some of which can be drug limiting. Additional antifungal therapies with enhanced fungal spectrum of activity and decreased rates of adverse effects are warranted.

Invasive fusariosis - Nucci, Marcio; Anaissie, Elias (Clinical Microbiology Reviews, 2023)
SUMMARY Invasive fusariosis is a serious invasive fungal disease, affecting immunocompetent and, more frequently, immunocompromised patients. Localized disease is the typical clinical form in immunocompetent patients. Immunocompromised hosts at elevated risk of developing invasive fusariosis are patients with acute leukemia receiving chemotherapeutic regimens for remission induction, and those undergoing allogeneic hematopoietic cell transplant. In this setting, the infection is usually disseminated with positive blood cultures, multiple painful metastatic skin lesions, and lung involvement. Currently available antifungal agents have poor in vitro activity against Fusarium species, but a clear-cut correlation between in vitro activity and clinical effectiveness does not exist. The outcome of invasive fusariosis is largely dependent on the resolution of immunosuppression, especially neutrophil recovery in neutropenic patients.

Long-term dalbavancin for suppression of Gram-positive chronic left ventricular assist device infections - Rowe, Sarah; Green, Sarah; Albrecht, Benjamin; Pouch, Stephanie M (Open Forum Infectious Diseases, 2023)
Infection is the leading cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). Prolonged suppressive therapy should be strongly considered and is often utilized in patients with recurrent infections when source control cannot be achieved. Dalbavancin is a promising option in VAD patients requiring prolonged durations of antibiotic therapy, especially when no oral alternatives are available.This case series included eight patients receiving dalbavancin for the chronic suppression of Gram-positive infections at Emory University Hospital and Emory St. Joseph’s Hospital.The overall incidence of breakthrough infections occurred in five out of the eight patients included in the study. One patient experienced an early breakthrough infection within 1 month of dalbavancin initiation. Another patient experienced a breakthrough infection within 3 and 6 months of dalbavancin initiation and the final three patients experienced a breakthrough infection within 6 and 12 months. The average duration of dalbavancin suppression therapy amongst all patients was 229 days and no adverse effects were reported.Dalbavancin is a promising option in patients who require long-term suppression for chronic Gram-positive LVAD infections given its unique pharmacokinetic profile and excellent tissue penetration. The utilization of biweekly dalbavancin infusions in our 8 patients prevented infection for an extended period of time despite some of the patients not being able to consistently receive infusions. Larger studies are needed to determine the efficacy and safety of utilizing dalbavancin for long term suppression of Gram-positive LVAD infections.

Phage Therapy in Lung Transplantation: Current Status and Future Possibilities - Aslam, Saima (Clinical Infectious Diseases, 2023)
Patients with chronic lung disease and lung transplantation have high rates of colonization and infection from multidrug-resistant (MDR) organisms. This article summarizes the current state of knowledge regarding phage therapy in the setting of lung transplantation. Phage therapy has been used in several lung transplant candidates and recipients on a compassionate use basis targeting mostly MDR gram-negative infections and atypical mycobacterial infections with demonstrated clinical safety. Phage biodistribution given intravenously or via nebulization has not been extensively studied, though preliminary data are presented. Phage interacts with both the innate and adaptive immune system; current literature demonstrates the development of serum neutralization in some cases of phage therapy, although the clinical impact seems variable. A summary of current clinical trials involving patients with chronic lung disease is presented, though none are specifically targeting lung transplant candidates or recipients. In addition to treatment of active infections, a variety of clinical scenarios may benefit from phage therapy, and well-designed clinical trials involving this vulnerable patient population are needed: pre- or peritransplantation use of phage in the setting of MDR organism colonization may lead to waitlisting of candidates currently declined by many centers, along with potential reduction of waitlist mortality rates and posttransplant infections; phage may be used for biofilm-related bronchial stent infections; and, finally, there is a possibility that phage use can affect allograft function and chronic rejection.

Superior Accuracy of Aspergillus Plasma Cell-Free DNA Polymerase Chain Reaction Over Serum Galactomannan for the Diagnosis of Invasive Aspergillosis - Mah, Jordan; Nicholas, Veronica; Tayyar, Ralph; Moreno, Angel; Murugesan, Kanagavel; Budvytiene, Indre; Banaei, Niaz (Clinical Infectious Diseases, 2023)
Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice.We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan.Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7–95.7) and 93.1% (121 of 130; 95% CI, 87.4–96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3–82.1) and 89.8% (53 of 59; 95% CI, 79.5–95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9–98.5) in patients with a new diagnosis of IA.Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA.

Renal Transplantation in Patients With Tuberculosis: A Single-center Experience From an Endemic Region - Gadde, Ashwini B.; Jha, Pranaw Kumar; Bansal, Shyam B.; Rana, Abhyudaysingh; Jain, Manish; Bansal, Dinesh; Yadav, Dinesh Kumar; Mahapatra, Amit Kumar; Sethi, Sidharth Kumar; Kher, Vijay (Transplantation Direct, 2023)
Background. Despite being a common infection in end-stage kidney disease patients, there are no evidence-based guidelines to suggest the ideal time of transplantation in patients on antitubercular therapy (ATT). This study aimed to examine the outcome of transplantation in patients while on ATT compared with those without tuberculosis (TB). Methods. This was a retrospective study. Renal transplant recipients transplanted while on ATT were compared with a 1:1 matched group (for age, sex, diabetic status, and type of induction agent) of patients without TB at the time of transplant. Patient outcomes included relapse of TB and graft and patient survival. Results. There were 71 patients in each group. The mean duration for which ATT was given pretransplant was 3.8 ± 2.47 mo. The average total duration of ATT received was 12.27 ± 1.25 mo. Mortality in both the groups was similar (8.4% in the TB group versus 4.5% in the non-TB group; P = 0.49). None of the surviving patients had recurrence of TB during the follow-up. Death-censored graft survival (98.5% in the TB group versus 97% in the non-TB group; P = 1) and biopsy-proven acute rejection rates (9.86% in the TB group versus 8.45% in the non-TB group; P = 1) were also similar in both the groups. Conclusions. Successful transplantation in patients with end-stage kidney disease on ATT is possible without any deleterious effect on patient and graft survival and no risk of disease recurrence. Multicentric prospective studies are needed.

How I treat posttransplant lymphoproliferative disorder - Amengual, Jennifer E.; Pro, Barbara (Blood, 2023)
Abstract Posttransplant lymphoproliferative disorder (PTLD) is an important and potentially life-threatening complication of solid organ transplant and hematopoietic stem cell transplant (HSCT). Given the heterogeneity of PTLD and the risk of infectious complications in patients with immunosuppression, the treatment of this disease remains challenging. Monomorphic PTLD and lymphoma of B-cell origin account for the majority of cases. Treatment strategies for PTLD consist of response-adapted, risk-stratified methods using immunosuppression reduction, immunotherapy, and/or chemotherapy. With this approach, ∼25% of the patients do not need chemotherapy. Outcomes for patients with high risk or those who do not respond to frontline therapies remain dismal, and novel treatments are needed in this setting. PTLD is associated with Epstein-Barr virus (EBV) infection in 60% to 80% of cases, making EBV-directed therapy an attractive treatment modality. Recently, the introduction of adoptive immunotherapies has become a promising option for refractory cases; hopefully, these treatment strategies can be used as earlier lines of therapy in the future.

In vitro susceptibility patterns for slowly growing non-tuberculous mycobacteria in the USA from 2018 to 2022 - Calado Nogueira De Moura, Vinicius; Nguyen, Minh-Vu H; Hunkins, Joshua J; Daley, Charles L; Khare, Reeti (Journal of Antimicrobial Chemotherapy, 2023)
Background: Treatment of slowly growing non-tuberculous mycobacteria (SGM) is challenging. In vitro antimicrobial susceptibility testing (AST) is needed to optimize a multidrug regimen but requires weeks to result. Aggregated AST patterns, or an antibiogram, of SGM would be helpful to providers. Objectives: We aggregated and analysed human SGM isolates sent to our laboratory from across the USA between 2018 and 2022 to describe their in vitro susceptibility patterns and construct an antibiogram. Methods: SGM isolates’ species/subspecies and mutations in rrs or rrl were identified by a line probe assay. AST was done primarily by broth microdilution and interpreted using the latest CLSI guideline. Mutational and AST results for SGM with ≥15 isolates were collated and analysed with descriptive statistics. Results: There were 32 different species/subspecies of SGM from 10 131 isolates between January 2018 and December 2022 from across the USA, 80% of which were from organisms in Mycobacterium avium complex (MAC). Most specimens were sputum and came from Florida (2892). MAC ranged from 94% to 100% susceptible to clarithromycin, 64% to 91% to amikacin, 2% to 31% to linezolid, and 4% to 41% to moxifloxacin. Non-MAC SGM ranged from 82% to 100% susceptible to clarithromycin, 49% to 100% to amikacin, and 76% to 100% to rifabutin, but susceptibilities to other antimicrobials varied widely. WT rrs and rrl predicted >96% of phenotypic non-resistance to amikacin and clarithromycin, respectively, whereas mutant genotypes predicted >90% of phenotypic resistance. Conclusions: Most SGM are likely to be susceptible to clarithromycin and amikacin, complementing their treatment guidance by mycobacterial experts. Molecular identification of resistant genotypes is accurate and helpful. This antibiogram for SGM will help providers.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes - El Ghali, Amer; Morrisette, Taylor; Alosaimy, Sara; Lucas, Kristen; Tupayachi-Ortiz, Maria G.; Vemula, Raaga; Wadle, Carly; Philley, Julie V.; Mejia-Chew, Carlos; Hamad, Yasir; Stevens, Ryan W.; Zeuli, John D.; et al. (Antimicrobial Agents and Chemotherapy, 2023)
Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49–67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4–14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients - Feldman, Amy G.; Beaty, Brenda L.; Ferrolino, Jose A.; Maron, Gabriela; Weidner, Hillary K.; Ali, Saira A.; Bitterfeld, Leandra; Boulware, Mary Alice; Campbell, Kathleen M.; Carr, Emily; Chapman, Shelley; Chang, Yeh-Chung; et al. (JAMA Network Open, 2023)
This cohort study assesses the safety and immunogenicity of live viral vaccines in pediatric liver and kidney transplant recipients.

Is short-course antibiotic therapy suitable for Pseudomonas aeruginosa bloodstream infections in onco-hematology patients with febrile neutropenia? Results of a multi-institutional analysis - Feng, Xiaomeng; Qian, Chenjing; Fan, Yuping; Li, Jia; Wang, Jieru; Lin, Qingsong; Jiang, Erlie; Mi, Yingchang; Qiu, Lugui; Xiao, Zhijian; Wang, Jianxiang; Hong, Mei; et al. (Clinical Infectious Diseases, 2023)
Several studies have suggested that short-course antibiotic therapy was effective in Pseudomonas aeruginosa (PA) bloodstream infections (BSI) in immunocompetent patients. While similar studies in patients with hematological malignancies were rare.This cohort study included onco-hematology patients at two hematology centers in China. Inverse probability of treatment weighting was used to balance the confounding factors. Multivariate regression model was used to evaluate the effect of short-course antibiotic therapy on clinical outcomes.434 patients met eligibility criteria (short-course, 7-11 days, n=229; prolonged, 12-21 days, n=205). In the weighted cohort, the univariate and multivariate analysis indicated that short course antibiotic therapy had similar outcomes to the prolonged course. The recurrent PA infection at any site or mortality within 30 days of completing therapy occurred in 8 (3.9%) patients in the short-course group and in 10 (4.9%) in the prolonged-course group (p = 0.979). The recurrent infection within 90 days occurred in 20 (9.8%) patients in the short-course group and in 13 (6.3%) patients in the prolonged-course group (p =0.139), and the recurrent fever within 7 days occurred in 17 (8.3%) patients in the short-course group and in 15 (7.4%) in the prolonged-course group (p = 0.957). On average, patients who received short-course antibiotic therapy spent 3.3 fewer days in the hospital (p<0.001).In the study, short-course therapy was non-inferior to prolonged-course therapy in terms of clinical outcomes. However, due to its biases and limitations, further prospective randomized controlled trials are needed to generalize our findings.

Breakthrough invasive fungal infections on isavuconazole prophylaxis in hematologic malignancy & hematopoietic stem cell transplant patients - Khatri, Akshay M.; Natori, Yoichiro; Anderson, Anthony; Jabr, Ra'ed; Shah, Shreya A.; Natori, Akina; Chandhok, Namrata S.; Komanduri, Krishna; Morris, Michele I.; Camargo, Jose F.; Raja, Mohammed (Transplant Infectious Disease, 2023)
Abstract Background Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side‐effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported. Methods In this single‐center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs. Results We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21–91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs–nine proven [ Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus , and six possible infections. Twelve patients were neutropenic for a median of 28 (8–253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 μg/mL) were comparable to industry‐sponsored clinical trials. All‐cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co‐infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups. Conclusion ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side‐effect and drug‐interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs. image

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023) - Senneville, Éric; Albalawi, Zaina; van Asten, Suzanne A; Abbas, Zulfiqarali G; Allison, Geneve; Aragón-Sánchez, Javier; Embil, John M; Lavery, Lawrence A; Alhasan, Majdi; Oz, Orhan; Uçkay, Ilker; Urbančič-Rovan, Vilma; et al. (Clinical Infectious Diseases, 2023)
The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus.The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations.The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems.We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand - Coussement, Julien; Heath, Christopher H; Roberts, Matthew B; Lane, Rebekah J; Spelman, Tim; Smibert, Olivia C; Longhitano, Anthony; Morrissey, Orla; Nield, Blake; Tripathy, Monica; Davis, Joshua S; Kennedy, Karina J; et al. (Clinical Infectious Diseases, 2023)
Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete.We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included.Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89).Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

American Society of Transplantation and Cellular Therapy Series: #7 - Management of Respiratory Syncytial Virus Infections in Hematopoietic Cell Transplant Recipients - Chaer, Firas El; Kaul, Daniel R.; Englund, Janet A.; Boeckh, Michael; Batista, Marjorie V.; Seo, Susan K.; Carpenter, Paul A.; Navarro, David; Hirsch, Hans H.; Ison, Michael G.; Papanicolaou, Genovefa A.; Chemaly, Roy F. (Transplantation and Cellular Therapy, 2023)
The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy (ASTCT) partnered with its Transplant Infectious Disease Special Interest Group (TID-SIG) to update the 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A new approach was adopted to better serve clinical providers by publishing each standalone topic in the infectious disease series in a concise format of frequently asked questions (FAQ), tables, and figures. Experts in HCT and infectious diseases identified FAQs and then provided answers based on the strength of the recommendation and the level of supporting evidence. In the seventh guideline in the series, we focus on the respiratory syncytial virus (RSV) with FAQs addressing epidemiology, clinical diagnosis, prophylaxis, and treatment. Special consideration was given to RSV in pediatric, cord blood, haploidentical, and T cell-depleted HCT and chimeric antigen receptor T cell therapy recipients, as well as to identify future research directions.

Real world experience with conversion from valganciclovir to letermovir for cytomegalovirus prophylaxis: Letermovir reverses leukopenia and avoids mycophenolate dose reduction - Jorgenson, Margaret R.; Descourouez, Jillian L.; Saddler, Christopher M.; Smith, Jeannina A.; Odorico, Jon S.; Rice, John P.; Mandelbrot, Didier A. (Clinical Transplantation, 2023)
Purpose: Valganciclovir (VGC) is the gold-standard for cytomegalovirus (CMV) prophylaxis (PPX) after solid organ transplant (SOT). Letermovir (LTV) was recently approved in high-risk kidney transplant and has reduced myelosuppressive toxicity. Conversion from VGC to LTV may be pursued in the setting of leukopenia. It is unknown if this strategy is effective. Methods: Adult patients receiving abdominal SOT were included if converted from VGC to LTV between January 1, 2018 and January 31, 2023. Primary objective was to describe the impact of LTV conversion as measured by WBC recovery, mycophenolate modification, and use of GCSF, and prophylaxis efficacy assessed by course completion and breakthrough DNAemia. Secondary objective was to evaluate rates of post-prophylaxis CMV. Results: Seventy five SOT recipients met inclusion criteria. Mean change in WBC in response to LTV conversion by day 14 was +2.02 ± 2.52 k/uL. 75%(56/75) of the population did not require mycophenolate adjustment or had their dose increased after conversion. GCSF was required in 38.7%(29/75) prior to conversion; only 21.3%(16/75) of patients required GCSF after conversion. Early termination was uncommon, 14.7%(11/75) stopped due to lack of ongoing insurance approval, only one patient stopped due to adverse effects (1.3%). One patient had clinically significant breakthrough (1.3%) that was successfully managed with VGC. Incidence of post prophylaxis CMV was 40%. Conclusion: Withholding of VGC with LTV conversion may improve leukopenia without need for additional supportive measures. Most importantly, this strategy avoided additional mycophenolate modifications. In our study, LTV was associated with low rates of breakthrough. Post-prophylaxis CMV was similar to VGC prophylaxis.

Aspectos básicos de la vacunación contra la viruela símica (mpox en inglés) | Viruela símica (mpox en inglés) | Poxvirus | CDC - CDC (2023)
Mpox (monkeypox) is a viral disease that occurs mostly in central and western Africa. It was first identified in laboratory monkeys. However, it is much more common among animals such as rats, mice, rabbits, and the African Squirrel.

RSV Infection in Older Adults - Linder, Kathleen A.; Malani, Preeti N. (JAMA, 2023)
Respiratory syncytial virus (RSV) causes respiratory infections in humans.

Beginners guide to protocol writing in transplant infectious diseases - Kumar, Rebecca N.; Gorsline, Chelsea A.; Harris, Courtney E. (Transplant Infectious Disease, 2023)
Creating protocols surrounding the guidance of the prevention and treatment of infections in transplantation is an integral part of being a transplant infectious disease physician. This piece outlines the key components for success in developing a protocol, with an example protocol and protocol template available for readers. Collaborating effectively within the multi-disciplinary team to develop, implement, and assess the efficacy of a protocol is a skill that enhances the relationship with our transplantation colleagues and improves patient outcomes by standardizing the care delivered.

Immune monitoring-guided vs fixed duration of antiviral prophylaxis against cytomegalovirus in solid-organ transplant recipients. A Multicenter, Randomized Clinical Trial - Manuel, Oriol; Laager, Mirjam; Hirzel, Cédric; Neofytos, Dionysios; Walti, Laura N; Hoenger, Gideon; Binet, Isabelle; Schnyder, Aurelia; Stampf, Susanne; Koller, Michael; Mombelli, Matteo; Kim, Min Jeong; et al. (Clinical Infectious Diseases, 2023)
The use of assays detecting cytomegalovirus (CMV)-specific T-cell-mediated immunity may individualize the duration of antiviral prophylaxis in transplant recipients.In this open-label randomized trial, adult kidney and liver transplant recipients from six centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving anti-thymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune-monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV-specific interferon gamma release assay (T-Track® CMV); prophylaxis in the intervention group was stopped if the assay was positive. The primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus.Overall, 193 patients were randomized (92 in the immune-monitoring and 101 in the control group) of which 185 had evaluation of the primary endpoint (87 and 98 patients, respectively). Clinically significant CMV infection occurred in 26/87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32/98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference -0.1, 95%CI -13.0%, 12.7%; p = 0.064). The duration of antiviral prophylaxis was shorter in the immune-monitoring group (adjusted difference -26.0 days, 95%-CI -41.1 to -10.8 days, p < 0.001).Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary endpoint of CMV infection.

Mucormycosis in 2023: an update on pathogenesis and management - Alqarihi, Abdullah; Kontoyiannis, Dimitrios P.; Ibrahim, Ashraf S. (Frontiers in Cellular and Infection Microbiology, 2023)
Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with Rhizopus , Mucor , and Lichtheimia , accounting for > 90% of all cases. MCR is seen in patients with severe immunosuppression such as those with hematologic malignancy or transplantation, Diabetes Mellitus (DM) and diabetic ketoacidosis (DKA) and immunocompetent patients with severe wounds. The recent SARS COV2 epidemy in India has resulted in a tremendous increase in MCR cases, typically seen in the setting of uncontrolled DM and corticosteroid use. In addition to the diversity of affected hosts, MCR has pleiotropic clinical presentations, with rhino-orbital/rhino-cerebral, sino-pulmonary and necrotizing cutaneous forms being the predominant manifestations. Major insights in MCR pathogenesis have brought into focus the host receptors (GRP78) and signaling pathways (EGFR activation cascade) as well as the adhesins used by Mucorales for invasion. Furthermore, studies have expanded on the importance of iron availability and the complex regulation of iron homeostasis, as well as the pivotal role of mycotoxins as key factors for tissue invasion. The molecular toolbox to study Mucorales pathogenesis remains underdeveloped, but promise is brought by RNAi and CRISPR/Cas9 approaches. Important recent advancements have been made in early, culture-independent molecular diagnosis of MCR. However, development of new potent antifungals against Mucorales remains an unmet need. Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals. Reversal of underlying immunosuppression, if feasible, rapid DKA correction and in selected patients, surgical debulking are crucial for improved outcomes.

Infections in haematology patients treated with CAR-T therapies: A systematic review and meta-analysis - Reynolds, Gemma K; Sim, Beatrice; Spelman, Tim; Thomas, Ashmitha; Longhitano, Anthony; Anderson, Mary Ann; Thursky, Karin; Slavin, Monica; Teh, Benjamin W (Critical Reviews in Oncology/Hematology, 2023)
A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for haematological malignancy. Meta-analysis of pooled incidence, using random effects model, was conducted. Cochran’s Q test examined heterogeneity. 2678 patients across 33 studies were included in the primary outcome. Forty-percent of patients (95% CI: 0.33 – 0.48) experienced an infection of any grade. Twenty-five percent of infection events (95% CI: 0.16 – 0.34) were severe. Late infections were as common as early infections (IRR = 0.86, 95% CI: 0.38 – 1.98). All-grade infections, bacterial and viral infections were highest in myeloma patients at 57%, 37% and 28% respectively. Patients with NHL more commonly experienced late infections. Pooled rate of invasive candidiasis/yeast infections was 2% in studies utilizing anti-yeast prophylaxis. This review identified a high rate of all-grade infections, moderate rate of severe infections, and myeloma as a high-risk haematological group.
Keywords: CAR-T; Cellular therapies; Infections; Lymphoma; Myeloma

Opciones de alimentos más seguras para personas con el sistema inmunitario debilitado | Food Safety | CDC - CDC (2023)

ß-D-Glucan Assay in the Cerebrospinal Fluid for the Diagnosis of Non-cryptococcal Fungal Infection of the Central Nervous System: A Retrospective Multicentric Analysis and a Comprehensive Review of the Literature - Bigot, Jeanne; Leroy, Jordan; Chouaki, Taieb; Cholley, Laurence; Bigé, Naïke; Tabone, Marie-Dominique; Brissot, Eolia; Thorez, Sophie; Maizel, Julien; Dupont, Hervé; Sendid, Boualem; Hennequin, Christophe; et al. (Clinical Infectious Diseases, 2023)
Background. Except for cryptococcosis, fungal infection of the central nervous system (FI-CNS) is a rare but severe complication. Clinical and radiological signs are non-specific, and the value of conventional mycological diagnosis is very low. This study aimed to assess the value of β1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal noncryptococcosis patients. Methods. Cases associated with BDG assay in the CSF performed in 3 French University Hospitals over 5 years were included. Clinical, radiological, and mycological results were used to classify the episodes as proven/highly probable, probable, excluded, and unclassified FI-CNS. Sensitivity and specificity were compared to that calculated from an exhaustive review of the literature. Results. In total, 228 episodes consisting of 4, 7, 177, and 40 proven/highly probable, probable, excluded, and unclassified FICNS, respectively, were analysed. The sensitivity of BDG assay in CSF to diagnose proven/highly probable/probable FI-CNS ranged from 72.7% [95% confidence interval {CI}: 43.4%‒90.2%] to 100% [95% CI: 51%‒100%] in our study and was 82% in the literature. For the first time, specificity could be calculated over a large panel of pertinent controls and was found at 81.8% [95% CI: 75.3%‒86.8%]. Bacterial neurologic infections were associated with several false positive results Conclusions. Despite its sub-optimal performance, BDG assay in the CSF should be added to the diagnostic armamentarium for FI-CNS.

Safer Food Choices for People With Weakened Immune Systems | Food Safety | CDC - CDC (2023)

Infectious complications of car T‐cell therapy: A longitudinal risk model - Czapka, Michael T.; Riedell, Peter A.; Pisano, Jennifer C. (Transplant Infectious Disease, 2023)
Abstract Background CAR T‐cell therapy, where a patient's own T cells are re‐engineered to express a receptor to a target of interest, is becoming an increasingly utilized cancer‐directed therapy. There are significant toxicities that contribute to a novel state of immunocompromise, leading to new patterns of infectious complications that require further detailed study. Methods We created a single‐center cohort of adult recipients of CD19‐directed CAR T‐cell therapy and assessed infectious outcomes, supportive care received, toxicities, and markers of immune function up to 2 years following CAR T‐cell therapy. Descriptive statistics were used as appropriate for analysis. We additionally conducted time‐to‐event analysis assessing time‐to‐first infection with either log‐rank testing or Cox regression with univariate analysis, before including significant predictors into a multivariate Cox model of time to infection. Results We identified 73 patients who received CD19‐directed CAR T‐cell therapy who predominantly had diffuse large B‐cell lymphoma. Within 30 days of cell infusion, bacterial and Candida infections were the most common, with 64% of infections due to these organisms. Between 30 days and 2 years postinfusion, respiratory viruses and pneumonia were the most frequent infections, with 68% of infections due to these etiologies. Receipt of tocilizumab, development of immune effector cell‐associated neurotoxicity syndrome (ICANS), or lower neutrophil count were associated with quicker onset of infection in a multivariate Cox model. image Conclusions Respiratory viruses remain an important infectious complication of CAR T‐cell therapy following the first year. The model may be a useful tool to identify patients at the highest risk of infection.

Letermovir for pre‐emptive cytomegalovirus therapy after allogeneic hematopoietic cell transplantation - Kaur, Raena; Purtill, Duncan; Cooney, Julian; Cannell, Paul; Wright, Matthew; Copeland, Tandy‐Sue; McGuire, Matthew; Boan, Peter (Transplant Infectious Disease, 2023)
Abstract Background Cytomegalovirus (CMV) is a common cause of morbidity after allogeneic haematopoietic cell transplantation (alloHCT). Pre‐emptive therapy (PET) with valganciclovir (VGC) is associated with haematological toxicity. Methods We included alloHCT patients from 2018 to 2021 where letermovir (LTV) was used for CMV PET because of cytopenias. Results Ten patients were included. Six received VGC prior to LTV. VGC was commenced at median d42, given for median 40 days. LTV was commenced at median d90, given for median 54 days. At commencement of antiviral, CMV viral load was higher for VGC at 3.7 log 10 IU/mL, compared to LTV at 2.9 log 10 IU/mL. Viral load reduction occurred at 0.18 log 10 IU/mL per week for VGC, compared to 0.17 log 10 IU/mL per week for LTV. There was no clinically significant CMV viremia after stopping LTV. Cytopenias improved on LTV. Conclusion LTV was effective in controlling CMV viremia when it was given at a lower starting CMV viral load and later post alloHCT than VGC. Further study is required of LTV as upfront PET following alloHCT. image

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis - Tekin, Aysun; Truong, Hong Hieu; Rovati, Lucrezia; Lal, Amos; Gerberi, Danielle J; Gajic, Ognjen; O’Horo, John C (Open Forum Infectious Diseases, 2023)
Pneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests’ performance in detecting PCP.Five databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used.Eleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90–0.99), and specificity was 0.96 (95% CI, 0.92–0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01–0.05) and 19.31 (95% CI, 10.26–36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78–0.99) and 0.93 (95% CI, 0.80–0.98) and a specificity of 0.96 (95% CI, 0.88–0.99) and 0.98 (95% CI, 0.76–1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90–0.98) and 0.94 (95% CI, 0.84–0.98), respectively. The overall confidence in the estimates was low.Despite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Mpox Vaccination Basics - CDC (Centers for Disease Control and Prevention, 2023)
Learn more about mpox in the United States.

Invasive fungal infections in liver diseases - Barros, Nicolas; Rosenblatt, Russell E.; Phipps, Meaghan M.; Fomin, Vladislav; Mansour, Michael K. (Hepatology Communications, 2023)
Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.

Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial - Boulware, David R; Atukunda, Mucunguzi; Kagimu, Enock; Musubire, Abdu K; Akampurira, Andrew; Tugume, Lillian; Ssebambulidde, Kenneth; Kasibante, John; Nsangi, Laura; Mugabi, Timothy; Gakuru, Jane; Kimuda, Sarah; et al. (Clinical Infectious Diseases, 2023)
Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed.In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA).We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin.Grade 3–4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P = .05), particularly for anemia (21% vs 44%; P = .01) and potassium (5% vs 17%; P = .04).This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin.NCT04031833.

Mpox Vaccine Recommendations - CDC (Centers for Disease Control and Prevention, 2023)
Learn more about mpox vaccine recommendations.

Recomendaciones sobre la vacuna contra la viruela símica - CDC (Centers for Disease Control and Prevention, 2023)
Más información sobre las recomendaciones de vacunación contra la viruela símica.

Antimicrobials in patients with hematologic malignancies and recipients of hematopoietic cell transplantation and other cellular therapies - Tverdek, Frank; Escobar, Zahra Kassamali; Liu, Catherine; Jain, Rupali; Lindsay, Julian (Transplant Infectious Disease, 2023)
Background: Appropriate use of antimicrobials for hematologic malignancy, hematopoietic stem cell transplant recipients, and other cellular therapies is vital, with infection causing significant morbidity and mortality in this unique population of immunocompromised hosts. However, often in this population the choice and management of antimicrobial therapy is complex. When selecting an antimicrobial agent, key considerations include the need for dose adjustments due to renal or hepatic impairment, managing drug interactions, the potential for additive drug toxicity among those receiving polypharmacy and therapeutic drug monitoring. Other factors include leveraging pharmacodynamic principles to enable optimization of directed therapy against challenging pathogens, as well as judicious use of antimicrobials to limit drug resistance and adverse drug reactions.

Respiratory virus infections after allogeneic stem cell transplantation: Current understanding, knowledge gaps, and recent advances - Piñana, Jose L.; Pérez, Ariadna; Chorão, Pedro; Guerreiro, Manuel; García‐Cadenas, Irene; Solano, Carlos; Martino, Rodrigo; Navarro, David; the Infectious Complications Subcommittee of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH‐TC) (Transplant Infectious Disease, 2023)
Before the COVID‐19 pandemic, common community‐acquired seasonal respiratory viruses (CARVs) were a significant threat to the health and well‐being of allogeneic hematopoietic cell transplant (allo‐HCT) recipients, often resulting in severe illness and even death. The pandemic has further highlighted the significant risk that immunosuppressed patients, including allo‐HCT recipients, face when infected with SARS‐CoV‐2. As preventive transmission measures are relaxed and CARVs circulate again among the community, including in allo‐HSCT recipients, it is crucial to understand the current state of knowledge, gaps, and recent advances regarding CARV infection in allo‐HCT recipients. Urgent research is needed to identify seasonal respiratory viruses as potential drivers for future pandemics.

Real-World use of Mold-Active Triazole Prophylaxis in the Prevention of Invasive Fungal Diseases: Results from a Subgroup Analysis of a Multicenter National Registry - Nguyen, M Hong; Ostrosky-Zeichner, Luis; Pappas, Peter G; Walsh, Thomas J; Bubalo, Joseph; Alexander, Barbara D; Miceli, Marisa H; Jiang, Jeanette; Song, Yi; Thompson III, George R (Open Forum Infectious Diseases, 2023)
Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed real-world use of mold-active triazoles (MATs) for the prevention of IFDs.This subgroup analysis of a multicenter, observational, prospective registry in the US from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient characteristics and patterns of MAT use. Exploratory assessments included the frequency of breakthrough IFDs, and MAT-related adverse drug reactions (ADRs).A total of 1177 patients (256 isavuconazole, 397 posaconazole, 272 voriconazole, and 252 multiple/sequenced MATs at/after index/enrollment) were included in the prophylaxis subgroup analysis. Patient characteristics were similar across MAT groups, but risk factors varied. Hematological malignancy predominated (76.5%) across all groups. Breakthrough IFDs occurred in 7.1% (73/1030) of patients with an investigator’s assessment (5.0% [11/221] isavuconazole; 5.3% [20/374] posaconazole; 4.0% [9/226] voriconazole; and 15.8% [33/209] multiple/sequenced MATs). Aspergillus (29.5% [18/61]) and Candida (36.1% [22/61]) species were the most common breakthrough pathogens recovered. ADRs were reported in 14.1% of patients, and discontinuation of MATs due to ADRs was reported in 11.1% of patients (2.0% [5/245] isavuconazole; 8.2% [30/368] posaconazole; and 10.1% [27/267] voriconazole).Breakthrough IFDs were uncommon in patients who received MATs for prophylaxis. Candida and Aspergillus species were the most commonly reported breakthrough pathogens. The discontinuation of MATs due to ADRs was infrequent. These findings support prophylactic strategies with isavuconazole, posaconazole, and voriconazole in high-risk patients.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement - McDonald, Emily G.; Aggrey, Gloria; Tarık Aslan, Abdullah; Casias, Michael; Cortes-Penfield, Nicolas; Dong, Mei Qin (Denise); Egbert, Susan; Footer, Brent; Isler, Burcu; King, Madeline; Maximos, Mira; Wuerz, Terence C.; et al. (JAMA Network Open, 2023)
Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence.To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength.This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches.A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)–only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions.In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Emerging Resistance Trends in Viridans Group Streptococci Bloodstream Infections Among Immunocompromised Children Receiving Levofloxacin Prophylaxis - Quintero, Ana M; Cruz Vidal, Diego A; Klamer, Brett G; Ardura, Monica I; Oyeniran, Sophonie J (Journal of the Pediatric Infectious Diseases Society, 2023)
Background. Levofloxacin prophylaxis (LVXp) is often used for patients with underlying leukemia and severe neutropenia to reduce the risk of fever and bacteremia. This study evaluated trends in viridans group streptococci (VGS) antibiotic susceptibilities over time and clinical outcomes of children with VGS bloodstream infections (BSIs) during institutional adoption of LVXp. Methods. VGS blood culture isolates between 1/1/2010 and 12/31/2021 with susceptibility testing reported were included. Available isolates were re-identified to the species level and additional susceptibility testing was performed. Demographic and clinical data were abstracted from medical records. Results: A total of 264 VGS BSI isolates were identified in immunocompromised (IC, n = 125) and non-immunocompromised subjects, (non-IC, n = 139). IC subjects had lower rates of VGS isolates susceptible (S) to LVX and higher minimum inhibitory concentration (MICs) to LVX (p = 0.004) and ciprofloxacin (p = 0.0005) compared with non-IC subjects. No other evaluated antibiotic had increased MICs in either group. Fifteen of 19 (74%) LVX not susceptible (NS) isolates occurred in IC subjects, 13 represented breakthrough infections. IC subjects had higher rates of VGS-related shock (p = 0.012), need for pressor support (p = 0.039), and longer duration of hospitalization than non-IC subjects (p < 0.001). Clinical outcomes were comparable between subjects with LVX S and NS VGS BSI isolates. Conclusions. VGS with reduced susceptibility to LVX emerged during institutional adoption of LVXp in high-risk children with immunocompromising conditions, but did not result in significant differences in clinical outcomes. Ongoing surveillance and susceptibility testing are critical in weighing the utility of LVXp against emerging antimicrobial resistance in this high-risk population.

Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients - Chou, Sunwen; Alain, Sophie; Cervera, Carlos; Chemaly, Roy F.; Kotton, Camille N.; Lundgren, Jens; Papanicolaou, Genovefa A.; Pereira, Marcus R.; Wu, Jingyang J.; Murray, Rose Ann; Buss, Neil E.; Fournier, Martha (The Journal of Infectious Diseases, 2023)
BACKGROUND: This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24% respectively cleared cytomegalovirus DNA at week 8 (treatment responders). METHODS: Baseline and post-treatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54 and UL27. RESULTS: At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n=1) and UL97 F342Y (n=3). Post-treatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 non-responders and 25 (86%) of the 29 non-responders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n=34), H411Y (n=26) and C480F (n=21), first detected 26 to 130 (median 56) days after starting maribavir. CONCLUSIONS: Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance. CLINICAL TRIALS REGISTRATION: NCT02931539 (SOLSTICE).
Keywords: Antiviral drug resistance; antiviral therapy; cytomegalovirus; maribavir

Living kidney donors with HIV: experience and outcomes from a case series by the HOPE in Action Consortium - Durand, Christine M.; Martinez, Nina; Neumann, Karl; Benedict, Reed C.; Baker, Arthur W.; Wolfe, Cameron R.; Stosor, Valentina; Shetty, Aneesha; Dietch, Zachary C.; Goudy, Leah; Callegari, Michelle A.; Massie, Allan B.; et al. (The Lancet Regional Health – Americas, 2023)
Publisher: Elsevier
Keywords: HIV Organ Policy Equity Act; HIV donation; HIV to HIV transplantation; HOPE Act; Living kidney donation; Transplantation from donors with HIV to recipients with HIV

Infectious Complications of Lung Transplant for Coronavirus Disease 2019–Associated Lung Injury: A Single-Center Case-Control Cohort Study - Osborn, Rebecca; Alamri, Maha; Tomic, Rade; Ison, Michael G (Clinical Infectious Diseases, 2023)
Lung transplantation is one of the only options for patients with severe coronavirus disease 2019 (COVID-19)–associated lung injury (CALI). Studies on patients who received a lung transplant for CALI have, to date, not looked at the infectious outcomes.After institutional review board approval, a retrospective case-control cohort study, matched 1:1, collected data on patients who underwent lung transplantation for CALI (case) and for non–COVID-19 end-stage lung disease (control) between 1 June 2020 and 1 April 2022 at a large academic hospital in Chicago. We assessed infectious complications and other key outcomes pre-transplant and for 1 year post-transplant.Among 78 patients (39 CALI and 39 matched control lung transplant patients), those in the CALI cohort were less likely to be vaccinated pre-transplant and were more likely to have diabetes, to be obese, to not be ambulatory, and to require pre-transplant extracorporeal membrane oxygenation and mechanical ventilation. Patients transplanted for CALI had higher rates of infection pre-transplant (66.7% vs 15.4% of patients in the control) and in the first 30 days post-transplant (43.6% vs 20.5%). Numbers and types of infection were similar in both groups at other time points. One-year mortality was similar for CALI and control groups (12.8% vs 10.3%, respectively).Patients who received a lung transplant for CALI are more deconditioned with prolonged hospital stays and experience more infectious complications immediately pre- and post-transplant. Infections due to multidrug-resistant organisms are important contributors to morbidity and mortality in this population. Antimicrobial stewardship is urgently needed.

Vaccines for COVID-19 - CDC (Vaccines for COVID-19, 2023)

Vacunas contra el COVID-19 - CDC (2023)

Upper and/or Lower Respiratory Tract Infection Caused by Human Metapneumovirus After Allogeneic Hematopoietic Stem Cell Transplantation - Piñana, Jose Luis; Tridello, Gloria; Xhaard, Aliénor; Wendel, Lotus; Montoro, Juan; Vazquez, Lourdes; Heras, Inmaculada; Ljungman, Per; Mikulska, Malgorzata; Salmenniemi, Urpu; Perez, Ariadna; Kröger, Nicolaus; et al. (The Journal of Infectious Diseases, 2023)
Background. Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. Methods. This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. Results. We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. Conclusions. These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.

Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management - Thompson, George R.; Jenks, Jeffrey D.; Baddley, John W.; Lewis, James S.; Egger, Matthias; Schwartz, Ilan S.; Boyer, Johannes; Patterson, Thomas F.; Chen, Sharon C.-A.; Pappas, Peter G.; Hoenigl, Martin (Clinical Microbiology Reviews, 2023)
Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (.70%), and presents numerous challenges during clinical care. Candida spp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed by Aspergillus and Histoplasma spp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use. The signs and symptoms of fungal endocarditis are nonspeciﬁc, and a high degree of clinical suspicion coupled with the judicious use of diagnostic tests is required for diagnosis. In addition to microbiological diagnostics (e.g., blood culture for Candida spp. or galactomannan testing and PCR for Aspergillus spp.), echocardiography remains critical for evaluation of potential infective endocarditis, although radionuclide imaging modalities such as 18F-ﬂuorodeoxyglucose positron emission tomography/computed tomography are increasingly being used. A multimodal treatment approach is necessary: surgery is usually required and should be accompanied by long-term systemic antifungal therapy, such as echinocandin therapy for Candida endocarditis or voriconazole therapy for Aspergillus endocarditis.

A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients - Kumar, Lakshin; Murray-Krezan, Cristina; Singh, Nina; Brennan, Daniel C.; Rakita, Robert M.; Dasgupta, Sayan; Fisher, Cynthia E.; Limaye, Ajit P. (Transplantation Direct, 2023)
Background. The optimal strategy for cytomegalovirus (CMV) disease prevention in CMV donor/recipient kidney transplant recipients remains uncertain. Conclusions of prior meta-analyses that CMV disease rates with preemptive therapy (PET) and universal prophylaxis (UP) were comparable may have been affected by inclusion of studies lacking key determinants of efficacy of the respective strategies. Methods. We conducted a systematic review and meta-analysis of PET with weekly CMV polymerase chain reaction monitoring for ≥3 mo and UP with 6 mo of valganciclovir. PubMed and Embase databases were reviewed from January 1, 2010, to April 1, 2022. Risk of bias was assessed with 3 instruments (Cochrane RoB, Cochrane RoBINS-I, and an instrument for assessing risk in observational studies). The primary outcome was CMV disease incidence by 1-y posttransplant. Secondary outcomes by 1-y were graft loss, acute allograft rejection, and mortality. Results were synthesized using generalized linear mixed model meta-analysis. PET studies were stratified into low-threshold (LT) and high-threshold (HT) PET based on the viral load threshold for initiation of antiviral therapy. Results. Twenty-five studies met inclusion criteria (6 PET, 19 UP). CMV disease incidence was significantly higher in HT (0.30 [95% confidence interval (CI), 0.22-0.39]) versus LT PET (0.06 [95% CI, 0.03-0.12]). LT PET was associated with a significantly lower CMV disease incidence (0.06 [95% CI, 0.03-0.12]) versus UP (0.21 [95% CI, 0.17-0.27]). Incidence of graft loss, acute allograft rejection, or mortality was not significantly different between LT PET and UP ( P > 0.05 for all comparisons). Receipt of lymphocyte-depleting antibodies was not associated with a significant difference in CMV disease incidence (odds ratio = 1.34 [95% CI, 0.80-2.25]). Conclusions. LT PET is associated with a significantly lower incidence of CMV disease compared to UP with similar rates of other clinical outcomes. These findings provide rationale and preliminary data for a randomized superiority trial of optimized LT-PET versus UP in donor seropositive recipient seronegative kidney transplant recipients.

Serial Quantitation of Plasma Microbial Cell-Free DNA Before and After Diagnosis of Pulmonary Invasive Mold Infections After Hematopoietic Cell Transplant - Heldman, Madeleine R; Ahmed, Asim A; Liu, Winnie; Vo, Alythia; Keane-Candib, Jacob; Stevens-Ayers, Terry; Boeckh, Michael; Blauwkamp, Timothy A; Fisher, Cynthia E; Hill, Joshua A (The Journal of Infectious Diseases, 2023)
Background. Plasma microbial cell-free DNA sequencing (mcfDNA-Seq) is a noninvasive test for microbial diagnosis of invasive mold infection (IMI). The utility of mcfDNA-Seq for predicting IMI onset and the clinical implications of mcfDNA concentrations are unknown. Methods. We retrospectively tested plasma from hematopoietic cell transplant (HCT) recipients with pulmonary IMI and ≥1 mold identified by mcfDNA-Seq in plasma collected within 14 days of clinical diagnosis. Samples collected from up to 4 weeks before and 4 weeks after IMI diagnosis were evaluated using mcfDNA-Seq. Results. Thirty-five HCT recipients with 39 IMIs (16 Aspergillus and 23 non-Aspergillus infections) were included. Pathogenic molds were detected in 38%, 26%, 11%, and 0% of samples collected during the first, second, third, and fourth week before clinical diagnosis, respectively. In non-Aspergillus infections, median mcfDNA concentrations in samples collected within 3 days of clinical diagnosis were higher in infections with versus without extrapulmonary spread (4.3 vs 3.3 log10 molecules per microliter [mpm], P = .02), and all patients (8/8) with mcfDNA concentrations >4.0 log10 mpm died within 42 days after clinical diagnosis. Conclusions. Plasma mcfDNA-Seq can identify pathogenic molds up to 3 weeks before clinical diagnosis of pulmonary IMI. Plasma mcfDNA concentrations may correlate with extrapulmonary spread and mortality in non-Aspergillus IMI.

Long-term Safety and Tolerability of Omadacycline for the Treatment of Mycobacterium abscessus Infections - Mingora, Christina M; Bullington, Wendy; Faasuamalie, Paige E; Levin, Adrah; Porter, Gabriella; Stadnik, Ryan; Varley, Cara D; Addrizzo-Harris, Doreen; Daley, Charles L; Olivier, Kenneth N; Winthrop, Kevin L; Dorman, Susan E; et al. (Open Forum Infectious Diseases, 2023)
Mycobacterium abscessus is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of M abscessus infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability.We conducted a multicenter retrospective chart review of adults with M abscessus infections. All patients treated with omadacycline as part of a multidrug therapeutic regimen through December 2021 were included. Clinical data from time of omadacycline initiation and up to 12 months of follow-up were collected. Descriptive statistics were performed.Analysis included 117 patients. Among patients with M abscessus isolate subspeciation, 58 of 71 (81.7%) were M abscessus spp abscessus. In isolates with reported drug susceptibility testing, 15 of 70 (21.4%) had confirmed susceptibility to macrolides. The most common site of infection was lungs. Median duration omadacycline treatment was 8 months (range, 0.25–33 months; interquartile range, 4–15 months). Omadacycline was discontinued in 60 patients (51.3%); 20 completed planned treatment course, 23 experienced intolerance or adverse event leading to drug cessation, and 17 stopped due to cost, death (unrelated to NTM infection or therapy), or another reason. In those with pulmonary disease, 44 of 95 (46%) had 1 or more negative cultures at time of final microbiological assessment, with 17 of 95 (18%) achieving culture conversion.This study reports data supporting long-term safety and tolerability of omadacycline along with signal of effectiveness in treatment of M abscessus infections.

Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae - Pérez-Nadales, Elena; Fernández-Ruiz, Mario; Natera, Alejandra M.; Gutiérrez-Gutiérrez, Belén; Mularoni, Alessandra; Russelli, Giovanna; Pierrotti, Ligia Camera; Pinheiro Freire, Maristela; Falcone, Marco; Tiseo, Giusy; Tumbarello, Mario; Raffaelli, Francesca; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2023)
We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.
Keywords: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Drug Combinations; Humans; INCREMENT-SOT project; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Sepsis; bloodstream infections; carbapenem-resistant Klebsiella pneumoniae; ceftazidime-avibactam; solid-organ transplantation

Prophylaxis Against Pneumocystis jirovecii Pneumonia in Adults - Zhou, Shiwei; Aitken, Samuel L. (JAMA, 2023)
This JAMA Insights Clinical Update discusses current recommendations regarding prevention of Pneumocystis pneumonia in patients who are immunocompromised.

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections - Cairns, Kelly A.; Udy, Andrew A.; Peel, Trisha N.; Abbott, Iain J.; Dooley, Michael J.; Peleg, Anton Y. (Clinical Microbiology Reviews, 2023)
Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Signiﬁcant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VREactive agents; however, there are signiﬁcant gaps in the literature for predicting antimicrobial efﬁcacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Seguridad de los alimentos | CDC - CDC (2023)
Each year, 1 in 6 Americans get sick from eating contaminated food. Visit CDC's food safety site for simple tips to help prevent food poisoning and for information on foodborne disease outbreaks.

Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial - Lafaurie, Matthieu; Chevret, Sylvie; Fontaine, Jean-Paul; Mongiat-Artus, Pierre; de Lastours, Victoire; Escaut, Lélia; Jaureguiberry, Stéphane; Bernard, Louis; Bruyere, Franck; Gatey, Caroline; Abgrall, Sophie; Ferreyra, Milagros; et al. (Clinical Infectious Diseases, 2023)
The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial.To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3–4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events.Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, –21.9 [95% confidence interval, −33.3 to −10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups.A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended.NCT02424461; Eudra-CT: 2013-001647-32.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019–Associated End-Stage Lung Disease in the United States - Okumura, Kenji; Jyothula, Soma; Kaleekal, Thomas; Dhand, Abhay (Clinical Infectious Diseases, 2023)
Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)–associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up.Characteristics of deceased donors and adult lung transplant recipients for COVID-19–associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non–COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection.During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non–COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non–COVID, 86.3%). Post-transplant, COVID-19–associated deaths were 9.2% of all deaths among lung transplant recipients.Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non–COVID-19 etiology.

Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis - Piché-Renaud, Pierre-Philippe; Yue Lee, Erika; Ji, Catherine; Qing Huang, Jenny Yu; Uleryk, Elizabeth; Teoh, Chia Wei; Morris, Shaun K.; Top, Karina A.; Upton, Julia E. M.; Vyas, Manav V.; Allen, Upton D. (American Journal of Transplantation, 2023)
This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.
Keywords: Varicella; chicken pox; immunization; live-attenuated vaccines; solid organ transplant

Guidance on the Use of Convalescent Plasma to Treat Immunocompromised Patients With Coronavirus Disease 2019 - Bloch, Evan M; Focosi, Daniele; Shoham, Shmuel; Senefeld, Jonathon; Tobian, Aaron A R; Baden, Lindsey R; Tiberghien, Pierre; Sullivan, David J; Cohn, Claudia; Dioverti, Veronica; Henderson, Jeffrey P; So-Osman, Cynthia; et al. (Clinical Infectious Diseases, 2023)
Abstract Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

Road map to success: Advice for transplant infectious diseases job interviews, negotiation, and early career development - Harris, Courtney E.; Kumar, Rebecca N.; Gorsline, Chelsea A. (Transplant Infectious Disease, 2023)

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial - Limaye, Ajit P.; Budde, Klemens; Humar, Atul; Vincenti, Flavio; Kuypers, Dirk R. J.; Carroll, Robert P.; Stauffer, Nicole; Murata, Yoshihiko; Strizki, Julie M.; Teal, Valerie L.; Gilbert, Christopher L.; Haber, Barbara A. (JAMA, 2023)
Valganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression.To compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor.Randomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022).Participants were randomized in a 1:1 ratio (stratified by receipt of lymphocyte-depleting induction immunosuppression) to receive letermovir, 480 mg, orally daily (with acyclovir) or valganciclovir, 900 mg, orally daily (adjusted for kidney function) for up to 200 days after transplant, with matching placebos.The primary outcome was CMV disease, confirmed by an independent masked adjudication committee, through posttransplant week 52 (prespecified noninferiority margin, 10%). CMV disease through week 28 and time to onset of CMV disease through week 52 were secondary outcomes. Exploratory outcomes included quantifiable CMV DNAemia and resistance. The rate of leukopenia or neutropenia through week 28 was a prespecified safety outcome.Among 601 participants randomized, 589 received at least 1 dose of the study drug (mean age, 49.6 years; 422 [71.6%] men). Letermovir (n = 289) was noninferior to valganciclovir (n = 297) for prevention of CMV disease through week 52 (10.4% vs 11.8% of participants with committee-confirmed CMV disease; stratum-adjusted difference −1.4% [95% CI, −6.5% to 3.8%]). No participants who received letermovir vs 5 participants (1.7%) who received valganciclovir developed CMV disease through week 28. Time to onset of CMV disease was comparable between the groups (hazard ratio, 0.90 [95% CI, 0.56-1.47]). Quantifiable CMV DNAemia was detected in 2.1% of participants in the letermovir group vs 8.8% in the valganciclovir group by week 28. Of participants evaluated for suspected CMV disease or CMV DNAemia, none (0/52) who received letermovir and 12.1% (8/66) who received valganciclovir had resistance-associated substitutions. The rate of leukopenia or neutropenia through week 28 was lower with letermovir vs valganciclovir (26% vs 64%; difference, −37.9% [95% CI, −45.1% to −30.3%]; P < .001). Fewer participants in the letermovir group than the valganciclovir group discontinued prophylaxis due to adverse events (4.1% vs 13.5%) or drug-related adverse events (2.7% vs 8.8%).Among adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication.ClinicalTrials.gov Identifier: NCT03443869; EudraCT: 2017-001055-30

Evaluating antimicrobial duration for Gram‐negative bacteremia in patients with neutropenia due to hematologic malignancy or hematopoietic stem cell transplantation - Ranganath, Nischal; Yetmar, Zachary A.; McCandless, Audrey R.; Rivera, Christina G.; Lahr, Brian D.; Tande, Aaron J.; Shah, Aditya S. (Transplant Infectious Disease, 2023)
Background: In the management of Gram-negative bloodstream infection (GN-BSI), short antimicrobial courses have been increasingly demonstrated to be non-inferior to prolonged therapy, with lower risk of Clostridioides difficile infection (CDI) and emergence of multi-drug resistant (MDR) organisms. However, immunocompromised hosts were excluded from these studies. We investigated outcomes of short (≤10 days), intermediate (11–14 days), and prolonged (≥15 days) antimicrobial durations for GN-BSI in neutropenic patients. Methods: A retrospective cohort study was conducted on neutropenic patients with monomicrobial GN-BSI between 2018 and 2022. The primary outcome was a composite of all-cause mortality and microbiologic relapse within 90 days after therapy completion. The secondary outcome was a composite of 90-day CDI and development of MDR-GN bacteria. Cox regression analysis with propensity score (PS) adjustment was used to compare outcomes between the three groups. Results: A total of 206 patients were classified into short (n = 67), intermediate (n = 81), or prolonged (n = 58) duration. Neutropenia was predominantly secondary to hematopoietic stem cell transplantation (48%) or hematologic malignancy (35%). The primary sources of infection included intra-abdominal (51%), vascular catheter (27%), and urinary (8%). Most patients received definitive therapy with cefepime or carbapenem. No significant difference in the primary composite endpoint was observed for intermediate versus short (PS-adjusted hazard ratio [aHR] 0.89; 95% confidence interval [95% CI] 0.39–2.03) or prolonged versus short therapy (PS-aHR 1.20; 95% CI 0.52–2.74). There was no significant difference in the secondary composite endpoint of CDI or MDR-GN emergence. Conclusion: Our data suggest that short antimicrobial courses had comparable 90-day outcomes as intermediate and prolonged regimens for GN-BSI among immunocompromised patients with neutropenia.

Donor‐derived fulminant herpes simplex virus hepatitis after liver transplantation: Two cases and review of literature - Reinhold, Ilana; Teasca, Laurent; Rodriguez, Elena Requejo; Berney, Thierry; Mueller, Nicolas J; Hilty, Matthias; Andermatt, Rea; Saro, Francesca; Dutkowski, Philipp; Müllhaupt, Beat; Van Delden, Christian; Swiss Transplant Cohort Study (STCS) (Transplant Infectious Disease, 2023)

Single High-dose of Liposomal Amphotericin B in HIV/AIDS-related Disseminated Histoplasmosis: a Randomized Trial - Pasqualotto, Alessandro C; Dalla Lana, Daiane; Godoy, Cassia S M; Leitão, Terezinha do Menino Jesus Silva; Bay, Monica B; Damasceno, Lisandra Serra; Soares, Renata B A; Kist, Roger; Silva, Larissa R; Wiltgen, Denusa; Melo, Marineide; Guimarães, Taiguara F; et al. (Clinical Infectious Diseases, 2023)
Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.Prospective randomized multicenter open-label trial of one or two-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) Single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14.A total of 118 subjects were randomizedMedian CD4+ counts and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for Single-dose L-AmB, 69% Two-dose L-AmB, and 74% Control arm (p=0.69). Overall survival on D14 was 89.0% (34/38) for Single-dose L-AmB, 78.0% (29/37) for Two-dose L-AmB, and 92.1% (35/38) for Control arm (p=0.82).One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection - Bhattacharya, Debika; Aronsohn, Andrew; Price, Jennifer; Lo Re, III, Vincent; the AASLD-IDSA HCV Guidance Panel (Clinical Infectious Diseases, 2023)
The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.

Prevalence of Ocular Candidiasis and Candida Endophthalmitis in Patients With Candidemia: A Systematic Review and Meta-Analysis - Phongkhun, Kasidis; Pothikamjorn, Thananop; Srisurapanont, Karan; Manothummetha, Kasama; Sanguankeo, Anawin; Thongkam, Achitpol; Chuleerarux, Nipat; Leksuwankun, Surachai; Meejun, Tanaporn; Thanakitcharu, Jaedvara; Walker, Morgan; Gopinath, Shilpa; et al. (Clinical Infectious Diseases, 2023)
Abstract Background Infectious diseases and ophthalmology professional societies have disagreed regarding ocular screening in patients with candidemia. We aimed to summarize the current evidence on the prevalence of ocular candidiasis (OC) and Candida endophthalmitis (CE) according to the standardized definitions. Methods A literature search was conducted from the inception date through 16 October 2022 using PubMed, Embase, and SCOPUS. Pooled prevalence of ocular complications was derived from generalized linear mixed models (PROSPERO CRD42022326610). Results A total of 70 and 35 studies were included in the meta-analysis for OC and concordant CE (chorioretinitis with vitreous involvement), respectively. This study represented 8599 patients with candidemia who underwent ophthalmologic examination. Pooled prevalences (95% CI) of OC, overall CE, concordant CE, and discordant CE were 10.7% (8.4–13.5%), 3.1% (2.1–4.5%), 1.8% (1.3–2.6%), and 7.4% (4.5–12%) of patients screened, respectively. Studies from Asian countries had significantly higher concordant CE prevalence (95% CI) of patients screened (3.6%; 2.9–4.6%) compared with studies from European countries (1.4%; .4–5%) and American countries (1.4%; .9–2.2%) (P <.01). Presence of total parenteral nutrition and Candida albicans was associated with CE, with pooled odds ratios (95% CI) of 6.92 (3.58–13.36) and 3.02 (1.67–5.46), respectively. Conclusions Prevalence of concordant CE overall and among Asian countries was 2 and 4 times higher than the prevalence previously reported by the American Academy of Ophthalmology (AAO) of <0.9%, respectively. There is an urgent need to study optimal screening protocols and to establish joint recommendations by the Infectious Diseases Society of America and AAO.

Review of Clinical and Laboratory Diagnostics for Coccidioidomycosis - McHardy, Ian H.; Barker, Bridget; Thompson, George R. (Journal of Clinical Microbiology, 2023)
Coccidioidomycosis is a fungal disease associated with soil exposure that frequently goes undiagnosed due at least in part to its nonspeciﬁc presentation and the lack of clinical suspicion by health care providers. Currently available diagnostics for coccidioidomycosis offer qualitative results that can suffer from low speciﬁcity, while semiquantitative assays are labor-intensive and complex and can require multiple days to complete. Furthermore, signiﬁcant confusion exists regarding the optimal diagnostic algorithms and appropriate usage of available diagnostic tests. This review aims to inform clinical laboratorians and treating clinicians about the current diagnostic landscape, appropriate diagnostic strategies, and future diagnostic directions for coccidioidomycosis, which is expected to become more prevalent due to increased migration into areas of endemicity and climate changes.

How I treat refractory CRS and ICANS after CAR T-cell therapy - Jain, Michael D.; Smith, Melody; Shah, Nirali N. (Blood, 2023)
The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities.

Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder - Yetmar, Zachary A.; Duffy, Dustin; Smith, Byron H.; Vikram, Holenarasipur R.; Brumble, Lisa; Limper, Andrew H.; Beam, Elena (Clinical Transplantation, 2023)
Background: Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). Methods: We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes. Results: Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count < .5 × 109/L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7–114.5; p = .014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2–20.7; p < .001). PJP was associated with mortality within 90 days of diagnosis (p < .001), but not after 90 days (p = .317). PJP was also associated with 90-day death-censored renal allograft loss (p = .026). Conclusions: PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90 days. PJP prophylaxis should be considered in SOT recipients with PTLD.

Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case‐control study - Yetmar, Zachary A.; Chesdachai, Supavit; Duffy, Dustin; Smith, Byron H.; Challener, Douglas W.; Seville, Maria Teresa; Bosch, Wendelyn; Beam, Elena (Clinical Transplantation, 2023)
Background: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. Methods: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients. Results: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35). Conclusions: Multiple measures of immunosuppression and lack of trimethoprimsulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Bacteremia During the First Year After Solid Organ Transplantation: An Epidemiological Update - Neofytos, Dionysios; Stampf, Susanne; Hoessly, Linard D; D’Asaro, Matilde; Tang, Gael Nguyen; Boggian, Katia; Hirzel, Cedric; Khanna, Nina; Manuel, Oriol; Mueller, Nicolas J; Van Delden, Christian (Open Forum Infectious Diseases, 2023)
Background There are limited contemporary data on the epidemiology and outcomes of bacteremia in solid organ transplant recipients (SOTr). Methods Using the Swiss Transplant Cohort Study registry from 2008 to 2019, we performed a retrospective nested multicenter cohort study to describe the epidemiology of bacteremia in SOTr during the first year post-transplant. Results Of 4383 patients, 415 (9.5%) with 557 cases of bacteremia due to 627 pathogens were identified. One-year incidence was 9.5%, 12.8%, 11.4%, 9.8%, 8.3%, and 5.9% for all, heart, liver, lung, kidney, and kidney-pancreas SOTr, respectively (P = .003). Incidence decreased during the study period (hazard ratio, 0.66; P < .001). One-year incidence due to gram-negative bacilli (GNB), gram-positive cocci (GPC), and gram-positive bacilli (GPB) was 5.62%, 2.81%, and 0.23%, respectively. Seven (of 28, 25%) Staphylococcus aureus isolates were methicillin-resistant, 2/67 (3%) enterococci were vancomycin-resistant, and 32/250 (12.8%) GNB produced extended-spectrum beta-lactamases. Risk factors for bacteremia within 1 year post-transplant included age, diabetes, cardiopulmonary diseases, surgical/medical post-transplant complications, rejection, and fungal infections. Predictors for bacteremia during the first 30 days post-transplant included surgical post-transplant complications, rejection, deceased donor, and liver and lung transplantation. Transplantation in 2014–2019, CMV donor-negative/recipient-negative serology, and cotrimoxazole Pneumocystis prophylaxis were protective against bacteremia. Thirty-day mortality in SOTr with bacteremia was 3% and did not differ by SOT type. Conclusions Almost 1/10 SOTr may develop bacteremia during the first year post-transplant associated with low mortality. Lower bacteremia rates have been observed since 2014 and in patients receiving cotrimoxazole prophylaxis. Variabilities in incidence, timing, and pathogen of bacteremia across different SOT types may be used to tailor prophylactic and clinical approaches.

Utility of urine cultures during febrile neutropenia workup in hematopoietic stem cell transplantation recipients without urinary symptoms - Tran, Mya; Palmer, Shannon; Moore, Dominic T; Bartelt, Luther; Friedland, Anne; Grgic, Tatjana; Lachiewicz, Anne; Ptachcinski, Jon; Sena, Arlene; Trepte, Morgan; Van Duin, David; Andermann, Tessa M; et al. (Open Forum Infectious Diseases, 2023)
Abstract The utility of obtaining screening urine cultures for febrile neutropenia (FN) during hematopoietic stem cell transplant (HCT) is unknown. In 667 adult HCT patients with FN, only 40 (6%) were found with bacteriuria. Antibiotics were modified in 3 patients (0.4%) based on urine cultures and none developed urinary-associated infectious complications.

Patients | Hand Hygiene | CDC (2023)
Patients can reduce the risk of infection by proper handwashing.

Transplanting hepatitis B surface antigen-positive livers in the United States: outcomes and opportunities - Bhatnagar, Anshul; Prakash, Sameer; Lymberopoulos, Peter; Goff, Cameron; Shaikh, Anjiya; Kim, Donghee; Ahmed, Aijaz; Berg, Carl; Naggie, Susanna; Kanwal, Fasiha; Cholankeril, George; Lee, Tzu-Hao (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2023)
Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B virus. The 1- and 3-year post-LT survival for hepatitis B virus-negative patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared with patients who received livers from hepatitis C virus viremic donors (96.5%/93.0%, P = .961/.427), donation after cardiac death donors (93.0%/86.0%, P = .651/.598), average-risk donors (89.5%/86.0%, P = 0.264/0.617), and a combination of extended-criteria donors, including donation after cardiac death, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P = .621/.785). Recipients of HBsAg+ livers have similar post-LT survival compared with those receiving other types of grafts. Increasing the utilization of HBsAg+ livers could safely expand the donor pool.
Keywords: extended-criteria donors; hepatitis B virus; liver transplantation; organ utilization; posttransplant survival

Therapy with Allogeneic SARS-CoV-2-specific T-cells for Persistent COVID-19 in Immunocompromised Patients - Haidar, Ghady; Jacobs, Jana L; Hughes Kramer, Kailey; Naqvi, Asma; Heaps, Amy; Parikh, Urvi; McCormick, Kevin D; Sobolewski, Michele D; Agha, Mounzer; Bogdanovich, Tatiana; Bushunow, Vasilii; Farah, Rafic; et al. (Clinical Infectious Diseases, 2023)
We administered SARS-CoV-2 VST under emergency IND to 6 immunocompromised patients with persistent COVID-19 and characterized clinical and virologic responses: three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VST in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to two courses of remdesivir and experienced sustained recovery after VST. The use VST in immunocompromised patient with persistent COVID-19 requires further study.

Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults - Walsh, Edward E.; Pérez Marc, Gonzalo; Zareba, Agnieszka M.; Falsey, Ann R.; Jiang, Qin; Patton, Michael; Polack, Fernando P.; Llapur, Conrado; Doreski, Pablo A.; Ilangovan, Kumar; Rämet, Mika; Fukushima, Yasushi; et al. (New England Journal of Medicine, 2023)
Keywords: Aged; Antibodies; Viral; Double-Blind Method; Humans; Injections; Intramuscular; Middle Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Tract Infections; Treatment Outcome; Vaccine Efficacy; Vaccines; Combined

Risk Factors and Outcomes of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study of United States Renal Data System Data - Friedman, Daniel Z P; Johnson, Bradley K; Beam, Elena; Kremers, Walter K; Vergidis, Paschalis (Clinical Infectious Diseases, 2023)
Background. Kidney transplant recipients are at increased risk for invasive aspergillosis (IA), a disease with poor outcomes and substantial economic burden. We aimed to determine risk factors for posttransplant IA by using a national database and to assess the association of IA with mortality and allograft failure. Methods. Using the United States Renal Data System database, we performed a retrospective case-control study of patients who underwent kidney transplant from 1998 through 2017. To evaluate risk factors for IA, we performed conditional logistic regression analysis by comparing characteristics between IA-infected patients and their matched uninfected controls. We performed Cox regression analysis to evaluate the effects of IA on mortality and death-censored allograft failure. Results. We matched 359 patients with IA to 1436 uninfected controls (1:4). IA was diagnosed at a median of 22.5 months (interquartile range, 5.4–85.2 months) after kidney transplant. Risk factors for IA were Black/African American race, duration of pretransplant hemodialysis, higher Elixhauser Comorbidity Index score, weight loss, chronic pulmonary disease, need for early posttransplant hemodialysis, and a history of cytomegalovirus infection. Receiving an allograft from a living donor was protective against IA. IA was a strong independent predictor of 1-year mortality (adjusted hazard ratio [aHR], 5.02 [95% confidence interval {CI}, 3.58–7.04], P < .001). Additionally, IA was associated with 1-year allograft failure (aHR, 3.37 [95% CI, 1.96–5.77], P < .001). Conclusions. Our findings emphasize the importance of timely transplant to mitigate the risk of posttransplant IA. An individualized approach to disease prevention is essential to decrease mortality and allograft failure.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients - Friedland, Anne E.; Maziarz, Eileen K.; Wolfe, Cameron R.; Patel, Chetan B.; Patel, Priyesh; Milano, Carmelo A.; Schroder, Jacob N.; Daneshmand, Mani A.; Wallace, Richard J.; Alexander, Barbara D.; Baker, Arthur W. (American Journal of Transplantation, 2023)
Publisher: Elsevier
Keywords: DL; ICD; ICM; MABC; Mycobacterium abscessus complex; Mycobacterium abscessus infections; NICM; NTM; OHT; VAD; driveline; implantable cardioverter-defibrillator; ischemic cardiomyopathy; nonischemic cardiomyopathy; nontuberculosis Mycobacterial infections; nontuberculous mycobacteria; orthotopic heart transplant; orthotopic heart transplantation; ventricular assist device

Swimming-related Illnesses | Healthy Swimming | Healthy Water | CDC - CDC (2023)

New ISHLT COVID-19 Therapeutics Guidance - Ging, Patricia; Ison, Michael; Patel, Jignesh; Campos, Silvia Vidal; Vos, Robin; Aslam, Saima (2023)

Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group - Kimura, Shun-ichi; Akahoshi, Yu; Shiratori, Souichi; Okinaka, Keiji; Harada, Kaito; Uchida, Naoyuki; Doki, Noriko; Ikegame, Kazuhiro; Nakamae, Hirohisa; Tanaka, Masatsugu; Takada, Satoru; Kawakita, Toshiro; et al. (Open Forum Infectious Diseases, 2023)
Background. α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients. Methods. Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019. Results. Noninfectious IP was observed in 694 patients at a median (range) of 63 (0–1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0–903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48–4.25), along with total body irradiation (>8 Gy; HR, 1.57; 95% CI, 1.18–2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004–1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45–0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49–0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P < .001). Conclusions. Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.

Cytomegalovirus Infections in Patients Treated With Immune Checkpoint Inhibitors for Solid Malignancies - Anastasopoulou, Amalia; Samarkos, Michael; Diamantopoulos, Panagiotis; Vourlakou, Christina; Ziogas, Dimitrios C; Avramopoulos, Pantelis; Kouzis, Panagiotis; Haanen, John; Gogas, Helen (Open Forum Infectious Diseases, 2023)
Cytomegalovirus (CMV) infection/disease has been repeatedly reported in patients treated with immune-checkpoint inhibitors (ICIs) and most commonly involves patients with relapsed/refractory (R/R) immune-related adverse events (irAEs). In the current study, we present a patient with melanoma who developed CMV gastritis during treatment with pembrolizumab in the absence of irAEs and without previous or current immunosuppression. Moreover, we review the literature regarding CMV infection/disease in patients treated with ICIs for solid malignancies. We present the currently available data on the pathogenesis, clinical characteristics, endoscopic findings, and histologic features and highlight the potential differences among cases complicating R/R irAEs versus those occurring in patients who are immunosuppression naive. Finally, we discuss the currently available data regarding potential useful diagnostic tools as well as the management of these patients.

The International Society for Heart and Lung Transplantation/Heart Failure Society of America Guideline on Acute Mechanical Circulatory Support - Bernhardt, Alexander M.; Copeland, Hannah; Deswal, Anita; Gluck, Jason; Givertz, Michael M.; Bernhardt, Alexander M.; Gluck, Jason; Garan, Arthur Reshad; Hall, Shelley; Hayanga, Awori; Knezevic, Ivan; Pappalardo, Federico; et al. (The Journal of Heart and Lung Transplantation, 2023)
Publisher: Elsevier
Keywords: ACHD; ACT; ADHF; AHA; AI; AMI; ARDS; American Heart Association; BMI; BiV; C. difficile; CO; CPB; CS; CT; CVP; CXR; Clostridium difficile infection; CrCl; DC cardioversion; DCCV; ECG; ECLS; ECMO; ELSO; EN; ESC; European Society of Cardiology; Extracorporeal Life Support Organization; FAC; GP; HF; IABP; ICH; INR; INTERMACS; IV; Interagency Registry for Mechanically Assisted Circulatory Support; LAP; LMWH; LV; LVAD; LVEDP; LVEF; MAP; MCS; MR; MS; MV; NIS; NSTEMI; Nationwide Inpatient Sample; PA; PAC; PAPi; PCI; PCWP; RCTs; RHC; ROSC; RV; RVAD; RVSWI; SC; SCAI; ST elevation myocardial infarction; STEMI; SVR; Society for Cardiovascular Angiography and Interventions; TAPSE; TDI; TEE; TEG; TTE; UFH; UTI; VA-ECMO; VAD; VKA; VTE; VV-ECMO; VWF; aPTT; activated clotting time; activated partial thromboplastin time; acute decompensated heart failure; acute myocardial infarction; acute respiratory distress syndrome; adult congenital heart disease; aortic insufficiency; biventricular; body mass index; cardiac output; cardiogenic shock; cardiopulmonary bypass; central venous pressure; chest radiograph; computerized tomography; creatinine clearance; eCPR

Intravesical aminoglycoside instillations as prophylaxis for recurrent urinary tract infection: patient satisfaction, long-term safety and efficacy - Bilsen, Manu P; van Uhm, Janneke I M; Stalenhoef, Janneke E; van Nieuwkoop, Cees; Groenwold, Rolf H H; Visser, Leo G; Lambregts, Merel M C (JAC-Antimicrobial Resistance, 2023)
Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial resistance, intravesical aminoglycoside instillations (IAIs) are a non-systemic alternative.To assess treatment satisfaction, long-term safety and efficacy of IAIs for recurrent UTI.We conducted a cohort study using data collected between January 2013 and June 2022 at the Leiden University Medical Center. Adult patients with recurrent UTI who received prophylactic IAI were eligible for inclusion. Treatment satisfaction was assessed through a survey. Data on serum aminoglycoside concentrations, cystoscopy results and number of recurrences were obtained through chart review. Number of recurrences and UTI characteristics were compared between patients on and off IAI using Poisson and logistic mixed effects models.Forty-four patients were included (median follow-up time 976 days) and 323 UTIs occurred during follow-up. Overall treatment satisfaction was high (median 79.2/100). All but one patient had undetectable serum aminoglycoside levels and no malignancies were found on follow-up cystoscopy. IAI increased the time to first recurrence (102 days versus 36 days, P = 0.02), reduced the number of recurrences (rate ratio 0.75, 95% CI 0.56–0.99, P = 0.04) and the necessity for systemic antibiotics (OR 0.33, 95% CI 0.13–0.86, P = 0.02).In patients with recurrent UTI, IAI was associated with high treatment satisfaction, and was found to be a safe and effective alternative to oral antimicrobial prophylaxis.

CMV Infection After Letermovir Primary Prophylaxis Discontinuation in Allogeneic Hematopoietic Cell Transplant Recipients - Chavaz, Lara; Royston, Léna; Masouridi-Levrat, Stavroula; Mamez, Anne-Claire; Giannotti, Federica; Morin, Sarah; Van Delden, Christian; Chalandon, Yves; Neofytos, Dionysios (Open Forum Infectious Diseases, 2023)
In this single-center study of 61 allogeneic hematopoietic cell transplant (HCT) recipients receiving letermovir primary cytomegalovirus (CMV) prophylaxis for the first 100 days, we report 23% incidence of clinically significant CMV infection during the first 100 days after letermovir discontinuation, predominately in haploidentical HCT recipients, without any associations with CMV-DNAemia under letermovir.

Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis - Lortholary, Olivier; El-Sissy, Carine; Leporrier, Jérémie; Sze Wah Wong, Sarah; Dannaoui, Eric; Fremeaux-Bacchi, Véronique; Aimanianda, Vishukumar (Open Forum Infectious Diseases, 2023)
Eculizumab, a recombinant humanized monoclonal antibody (mAb), is used for the treatment of patients (both adults and children) with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. This mAb binds to complement protein 5 (C5), thereby inhibiting its cleavage. On the other hand, one of the C5 cleavage products, C5a, is a potent anaphylatoxin with proinflammatory properties, involved in antimicrobial surveillance. Administration of eculizumab has been reported to make patients more susceptible to infection by encapsulated bacteria. Here, we are reporting an adult case of disseminated infection due to the encapsulated yeast Cryptococcus neoformans following eculizumab therapy and discuss its pathogenesis.

Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention - Wilson Dib, Rita; Ariza-Heredia, Ella; Spallone, Amy; Chemaly, Roy F (Open Forum Infectious Diseases, 2023)
Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor–modified T cells, natural killer cells, and genetically modified T-cell receptors are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune-related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventive and therapeutic options for common RVIs, and appropriate infection control and preventive strategies.

Fatal Human Rabies Infection with Suspected Host-mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure—Minnesota, 2021 - Holzbauer, Stacy M; Schrodt, Caroline A; Prabhu, Rajesh M; Asch-Kendrick, Rebecca J; Ireland, Malia; Klumb, Carrie; Firestone, Melanie J; Liu, Gongping; Harry, Katie; Ritter, Jana M; Levine, Min Z; Orciari, Lillian A; et al. (Clinical Infectious Diseases, 2023)
Conclusion: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized D impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is E any suspicion for immunocompromise.

Triple combination therapy with two antivirals and monoclonal antibodies for persistent or relapsed SARS-CoV-2 infection in immunocompromised patients - Mikulska, Malgorzata; Sepulcri, Chiara; Dentone, Chiara; Magne, Federica; Balletto, Elisa; Baldi, Federico; Labate, Laura; Russo, Chiara; Mirabella, Michele; Magnasco, Laura; Di Grazia, Carmen; Ghiggi, Chiara; et al. (Clinical Infectious Diseases, 2023)
Severely immunocompromised patients are at risk for prolonged or relapsed COVID-19 leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients.We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with two antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (Mabs), between February and October 2022. The main outcomes were virological response at day 14 (negative SARS-CoV-2 swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up.Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of two antivirals and Mabs and 4 received two antivirals only; in 20/22 (91%) two antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received second course of combination treatment. Response rate at day 14, 30 and last follow-up was, respectively, 75% (15/20 evaluable), 73% (16/22) and 82% (18/22). Day 14 and 30 response rates were significantly higher when combination therapy included Mabs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects: bradycardia leading to remdesivir discontinuation and myocardial infarction.Combination therapy including two antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and Mabs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

Mycoplasma hominis and Ureaplasma urealyticum infections in the immediate post‐lung transplant period: A case series and literature review - Divithotewala, Chandima; Sweeney, Emma L.; Burke, Andrew; Graves, Bianca; Stewart, Adam; Whiley, David; Heney, Claire; Hopkins, Peter M.; Chambers, Daniel C. (Transplant Infectious Disease, 2023)
Mycoplasma hominis and Ureaplasma species infections in the post-transplant setting are believed to be donor-derived and can be associated with poor outcomes. Difficulty in culturing and identifying these organisms is a significant barrier to diagnosis and early intervention. Tetracyclines, macrolides and fluoroquinolones are the mainstay treatments to cure these infections; however, there are increasing reports of antibiotic resistance. In this case series, we report our single-centre experience with M. hominis and U. urealyticum infection after lung transplantation (9 recipients, all men, mean age 56 years). Delayed diagnosis was common. Young donor age (mean age 23 yrs) and high-risk donor social history (67%) were repeatedly noted in these cases, and all infections were associated with significant morbidity (anastomosis and sternal wound infection, empyema, mediastinitis, pericarditis). Two patients died; with one directly related to Ureaplasma urealyticum infection. In conclusion post lung transplant M. hominis, and U. urealyticum infections are challenging and carry high morbidity. More prospective studies are required to assess the true prevalence, full spectrum of complications and utility of molecular diagnostics to aid early diagnosis and identify antibiotic susceptibility of Mycoplasma and Ureaplasma infections in the post-lung transplant setting.

Screening and Management of PTLD - Zaffiri, Lorenzo; Chambers, Eileen T. (Transplantation, 2023)
Posttransplant lymphoproliferative disorder (PTLD) represents a heterogeneous group of lymphoproliferative diseases occurring in the setting of immunosuppression following hematopoietic stem cells transplant and solid organ transplantation. Despite its overall low incidence, PTLD is a serious complication following transplantation, with a mortality rate as high as 50% in transplant recipients. Therefore, it is important to establish for each transplant recipient a personalized risk evaluation for the development of PTLD based on the determination of Epstein-Barr virus serostatus and viral load following the initiation of immunosuppression. Due to the dynamic progression of PTLD, reflected in the diverse pathological features, different therapeutic approaches have been used to treat this disorder. Moreover, new therapeutic strategies based on the administration of virus-specific cytotoxic T cells have been developed. In this review, we summarize the available data on screening and treatment to suggest a strategy to identify transplant recipients at a higher risk for PTLD development and to review the current therapeutic options for PTLD.

COVID-19 Vaccination Guidance For Patients - AST (2023)

Mold-Active Antifungal Prophylaxis in Pediatric Patients with Cancer or Undergoing Hematopoietic Cell Transplantation - Lehrnbecher, Thomas; Bochennek, Konrad; Groll, Andreas H. (Journal of Fungi, 2023)
Invasive fungal diseases (IFDs), in particular invasive mold infections, still pose considerable problems in the care of children and adolescents treated for cancer or undergoing hematopoietic cell transplantation. As these infections are difﬁcult to diagnose, and the outcomes for IFDs are still unsatisfactory, antifungal prophylaxis has become an important strategy in the clinical setting. Antifungal prophylaxis is indicated in patients at high risk for IFD, which is commonly deﬁned as a natural incidence of at least 10%. As there is a growing interest in pediatric-speciﬁc clinical trials and pediatric-speciﬁc guidelines, this review focuses on the available data of mold-active antifungal prophylaxis in children and adolescents. The data demonstrate that a major effort is needed to characterize the pediatric patient population in which the net effect of prophylactic antifungals will be beneﬁcial as well as to ﬁnd the optimal prophylactic antifungal compound and dosage.

Isavuconazole in the Treatment of Chronic Forms of Coccidioidomycosis - Heidari, Arash; Sharma, Rupam; Shakir, Qusai; Shah, Madiha; Clement, Josh; Donnelly, Monica; Reynolds, Trina; Trigg, Kate; Jolliff, Jeff; Kuran, Rasha; Johnson, Royce; Thompson, III, George R (Clinical Infectious Diseases, 2023)
Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles necessitating evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis.

Real-world Application of Oral Therapy for Infective Endocarditis: A Multicenter Retrospective, Cohort Study - Freling, Sarah; Wald-Dickler, Noah; Banerjee, Josh; Canamar, Catherine P; Tangpraphaphorn, Soodtida; Bruce, Dara; Davar, Kusha; Dominguez, Fernando; Norwitz, Daniel; Krishnamurthi, Ganesh; Fung, Lilian; Guanzon, Ashley; et al. (Clinical Infectious Diseases, 2023)
We sought to compare the outcomes of patients treated with intravenous (IV)-only vs. oral transitional antimicrobial therapy for infective endocarditis (IE) after implementing a new Expected Practice within The Los Angeles County Department of Health Services (LAC DHS).We conducted a multi-centered, retrospective cohort study of adults with definite or possible IE treated with IV-only vs. oral therapy at the three acute care, public hospitals in the LAC DHS system between December 2018 to June 2022. The primary outcome was clinical success at 90 days, defined as being alive, and without recurrence of bacteremia or treatment-emergent infectious complications.We identified 257 patients with IE treated with IV-only (n=211) or oral transitional (n=46) therapy who met study inclusion criteria. Study arms were similar for many demographics; however, the IV cohort was older, and had more aortic valve involvement, hemodialysis patients, and central venous catheters present. In contrast, the oral cohort had a higher percentage of IE caused by methicillin-resistant S. aureus. There was no significant difference between the groups in clinical success at 90 days or last follow-up. There was no difference in recurrence of bacteremia or readmission rates. However, patients treated with oral therapy had significantly fewer adverse events. Multivariable regression adjustments did not find significant associations between any selected variables and clinical success across treatment groups.These results demonstrate similar outcomes of real-world use of oral vs. IV-only therapy for IE, in accord with prior randomized controlled trials and meta-analyses.

Management of nontuberculous mycobacteria in lung transplant cases: an international Delphi study - Asif, Huda; Rahaghi, Franck F.; Ohsumi, Akihiro; Philley, Julie; Emtiazjoo, Amir; Hirama, Takashi; Baker, Arthur W.; Shu, Chin-Chung; Silveira, Fernanda; Poulin, Vincent; Rizzuto, Pete; Nagao, Miki; et al. (ERJ Open Research, 2023)
Rationale Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii. Methods Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to −5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <−4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated. Results Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx. Conclusion This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions. Tweetable abstract @ERSpublications click to tweetExperts recommend performing sputum cultures and a chest CT scan for NTM screening in lung transplant candidates. They recommend against absolute contraindication to lung transplantation even with multiple positive sputum cultures for NTM. https://bit.ly/3WaSwLe
Publisher: European Respiratory Society Section: Original research articles

Babesia microti Variant With Multiple Resistance Mutations Detected in an Immunocompromised Patient Receiving Atovaquone Prophylaxis - Holbrook, Nolan R; Klontz, Erik H; Adams, Gordon C; Schnittman, Samuel R; Issa, Nicolas C; Bond, Sheila A; Branda, John A; Lemieux, Jacob E (Open Forum Infectious Diseases, 2023)
We report Babesia microti genomic sequences with multiple mutations in the atovaquone-target region of cytochrome b, including a newly identified Y272S mutation, plus 1 mutation of undetermined significance in the azithromycin-associated ribosomal protein L4. The parasite was sequenced from an immunocompromised patient on prophylactic atovaquone for Pneumocystis pneumonia before diagnosis of babesiosis.

Risk Factors and Outcomes of Nocardiosis in Hematopoietic Stem Cell Transplantation Recipients - Yetmar, Zachary A.; Thoendel, Matthew J.; Bosch, Wendelyn; Seville, Maria Teresa; Hogan, William J.; Beam, Elena (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2023)
Publisher: Elsevier
Keywords: Graft-versus-host disease; Nocardia; Opportunistic infection; Stem cell transplantation; Trimethoprim-sulfamethoxazole

Banking on virus-specific T cells to fulfill the need for off-the-shelf cell therapies - Quach, David H.; Lulla, Premal; Rooney, Cliona M. (Blood, 2023)
Abstract Adoptively transferred virus-specific T cells (VSTs) have shown remarkable safety and efficacy for the treatment of virus-associated diseases and malignancies in hematopoietic stem cell transplant (HSCT) recipients, for whom VSTs are derived from the HSCT donor. Autologous VSTs have also shown promise for the treatment of virus-driven malignancies outside the HSCT setting. In both cases, VSTs are manufactured as patient-specific products, and the time required for procurement, manufacture, and release testing precludes their use in acutely ill patients. Further, Good Manufacturing Practices–compliant products are expensive, and failures are common in virus-naive HSCT donors and patient-derived VSTs that are rendered anergic by immunosuppressive tumors. Hence, highly characterized, banked VSTs (B-VSTs) that can be used for multiple unrelated recipients are highly desirable. The major challenges facing B-VSTs result from the inevitable mismatches in the highly polymorphic and immunogenic human leukocyte antigens (HLA) that present internally processed antigens to the T-cell receptor, leading to the requirement for partial HLA matching between the B-VST and recipient. HLA mismatches lead to rapid rejection of allogeneic T-cell products and graft-versus-host disease induced by alloreactive T cells in the infusion product. Here, we summarize the clinical outcomes to date of trials of B-VSTs used for the treatment of viral infections and malignancies and their potential as a platform for chimeric antigen receptors targeting nonviral tumors. We will highlight the properties of VSTs that make them attractive off-the-shelf cell therapies, as well as the challenges that must be overcome before they can become mainstream.

Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults - Papi, Alberto; Ison, Michael G.; Langley, Joanne M.; Lee, Dong-Gun; Leroux-Roels, Isabel; Martinon-Torres, Federico; Schwarz, Tino F.; Van Zyl-Smit, Richard N.; Campora, Laura; Dezutter, Nancy; De Schrevel, Nathalie; Fissette, Laurence; et al. (New England Journal of Medicine, 2023)
Keywords: Adjuvants; Immunologic; Aged; Antibodies; Viral; Humans; Internationality; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus; Human; Respiratory Tract Infections; Vaccine Efficacy

Improved Survival After Liver Transplantation for Patients With Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus Coinfection in the Integrase Strand Transfer Inhibitor and Direct-Acting Antiviral Eras - Jacob, Jake Sheraj; Shaikh, Anjiya; Goli, Karthik; Rich, Nicole E; Benhammou, Jihane N; Ahmed, Aijaz; Kim, Donghee; Rana, Abbas; Goss, John A; Naggie, Susanna; Lee, Tzu-Hao; Kanwal, Fasiha; et al. (Clinical Infectious Diseases, 2023)
People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear.This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. In secondary analysis, we compared the outcomes in the different eras with those of propensity score–matched control cohorts of LT recipients without HIV or HCV infection.LT recipients with HIV monoinfection did not experience a significant improvement in survival between the pre-INSTI and INSTI recipients with HIV (adjusted hazard ratio [aHR], 0.70 [95% confidence interval {CI}, .36–1.34]). However, recipients with HIV/HCV coinfection in the DAA era had a 47% reduction (aHR, 0.53 [95% CI, .31–9.2] in 1-year mortality compared with coinfected recipients in the pre-DAA era. Compared to recipients without HIV or HCV, HIV-monoinfected recipients had higher mortality during the pre-INSTI era, but survival was comparable between groups during the INSTI era. HIV/HCV-coinfected recipients also experienced comparable survival during the DAA era compared to recipients without HCV or HIV.Post-LT survival for people with HIV monoinfection and HIV/HCV coinfection has improved with the introduction of INSTI and DAA therapy, suggesting that LT has become safer in these populations.

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer - Maertens, Johan; Lodewyck, Tom; Donnelly, J Peter; Chantepie, Sylvain; Robin, Christine; Blijlevens, Nicole; Turlure, Pascal; Selleslag, Dominik; Baron, Frédéric; Aoun, Mickael; Heinz, Werner J; Bertz, Hartmut; et al. (Clinical Infectious Diseases, 2023)
Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown.Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization.Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%–98.3%) when compared with arm A (93.1%; 95% CI, 89.3%–95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%–10.8%) in arm B vs 6.6% (95% CI, 3.6%–9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001).The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

A Double-Blind Placebo-Controlled Trial of Fecal Microbiota Transplantation in Allogeneic Hematopoietic Cell Transplantation Recipients - Rashidi, Armin; Ebadi, Maryam; Rehman, Tauseef Ur; Elhusseini, Heba; Kazadi, David; Halaweish, Hossam; Khan, Mohammad H.; Hoeschen, Andrea; Cao, Qing; Luo, Xianghua; Holtan, Shernan Grace; Weisdorf, Daniel J.; et al. (Tandem Meetings, 2023)
Gut microbiota injury in allogeneic HCT recipients has been associated with adv...

Utility of deceased donor cultures in solid organ transplantation in preventing donor‐derived bacterial and fungal infectious diseases transmission - Boutin, Catherine‐Audrey; Pouch, Stephanie M.; Ison, Michael G. (Transplant Infectious Disease, 2023)
Deceased donor and organ perfusion fluid cultures are obtained in order to inform recipient antimicrobial management and therefore reduce the risk of donor-derived bacterial and fungal infections. However, important heterogeneity exists in laboratory practice across organ procurement organizations and clinical management of culture results across transplant centers. While not standardized, the clinical approach to donors with positive bacterial and/or fungal cultures should be informed by the risk of donor-derived infection (DDI) and the consequence of organ non-utilization and account for potential unintended effects of antimicrobial use in the recipient. In this review, we summarize the literature on bacterial and fungal DDIs, describe the significance of positive cultures by anatomic site, and summarize current guidance on the management of positive cultures from donors or preservation fluids.

BK DNAemia and native kidney polyomavirus nephropathy following lung transplantation - Dube, Geoffrey K.; Batal, Ibrahim; Shah, Lori; Robbins, Hilary; Arcasoy, Selim M.; Husain, Syed Ali (American Journal of Transplantation, 2023)
BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.
Keywords: clinical research/practice; infectious agents viral: BK/JC/polyoma; infectious disease; kidney (native) function/dysfunction; kidney transplantation/nephrology infection; lung transplantation/pulmonology

Noninfectious Pulmonary Complications after Hematopoietic Stem Cell Transplantation - Fraebel, Johnathan; Engelhardt, Brian G.; Kim, Tae Kon (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2023)
Publisher: Elsevier
Keywords: Hematopoietic stem cell transplantation; Pulmonary complications

Invasive Scedosporium and Lomentospora prolificans Infections in Australia: A Multicenter Retrospective Cohort Study - Neoh, Chin Fen; Chen, Sharon C A; Crowe, Amy; Hamilton, Kate; Nguyen, Quoc A; Marriott, Debbie; Trubiano, Jason A; Spelman, Tim; Kong, David C M; Slavin, Monica A (Open Forum Infectious Diseases, 2023)
Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure.We conducted a retrospective Australian-based observational study of proven/probable Scedosporium/L prolificans infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed.Of 61 infection episodes, 37 (60.7%) were attributable to L prolificans. Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) L prolificans infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) Scedosporium spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post–IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both P < .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%.Outcomes associated with Scedosporium/L prolificans infections is poor, particularly with L prolificans infections or in the highly immunosuppressed population.

Infectious diarrhea after allogeneic hematopoietic cell transplantation assessed by a multiplex polymerase chain reaction assay - Praet, Jens T. Van; Huysman, Andreas; Knijf, Eline De; Buyser, Stefanie De; Snauwaert, Sylvia; Droogenbroeck, Jan Van; Lodewyck, Tom; Schauwvlieghe, Alexander; Selleslag, Dominik; Reynders, Marijke (International Journal of Infectious Diseases, 2023)
Publisher: Elsevier
Keywords: Allogeneic hematopoietic cell transplantation; Infectious diarrhea; Multiplex polymerase chain reaction assay

Transplantid.net: A Pilot Crowdsourced, Living, Online Library of Resources for the Teaching and Practice of Transplant Infectious Diseases - Puius, Yoram A; Azar, Marwan M; Tsai, Helen; Vergidis, Paschalis; Harris, Courtney E; Anjan, Shweta; Barros, Nicolas; Belga, Sara; Chuang, Sally T; Czeresnia, Jonathan M; Goel, Shipra; Ince, Dilek; et al. (Open Forum Infectious Diseases, 2023)
The field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.

Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial - Veringa, Anette; Brüggemann, Roger J.; Span, Lambert F. R.; Biemond, Bart J.; de Boer, Mark G. J.; van den Heuvel, Edwin R.; Klein, Saskia K.; Kraemer, Doris; Minnema, Monique C.; Prakken, Niek H. J.; Rijnders, Bart J. A.; Swen, Jesse J.; et al. (International Journal of Antimicrobial Agents, 2023)
Objectives Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treatment is superior to standard treatment for invasive aspergillosis. Methods A multicentre (n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged ≥18 years treated with voriconazole. All patients received standard voriconazole dose at the start of treatment. Blood/serum/plasma was periodically collected after treatment initiation of voriconazole and repeated during treatment in both groups. The TDM group had measured voriconazole concentrations reported back, with dose adjustments made as appropriate, while the non-TDM group had voriconazole concentrations measured only after study completion. The composite primary endpoint included response to treatment and voriconazole treatment discontinuation due to an adverse drug reaction related to voriconazole within 28 days after treatment initiation. Results In total, 189 patients were enrolled in the study. For the composite primary endpoint, 74 patients were included in the non-TDM group and 68 patients in the TDM group. Here, no significant difference was found between both groups (P = 0.678). However, more trough concentrations were found within the generally accepted range of 1–6 mg/L for the TDM group (74.0%) compared with the non-TDM group (64.0%) (P < 0.001). Conclusions In this trial, TDM-guided dosing of voriconazole did not show improved treatment outcome compared with standard dosing. We believe that these findings should open up the discussion for an approach to voriconazole TDM that includes drug exposure, pathogen susceptibility and host defence. Clinical trial registration ClinicalTrials.gov registration no. NCT00893555.
Keywords: Haematological malignancy; Invasive fungal infection; Therapeutic drug monitoring; Voriconazole

Noroviral diarrhea in solid organ transplant recipients: An analysis of interventions and outcomes - Nair, Sashi N.; Bhaskaran, Archana; Chandorkar, Aditya; Fontana, Lauren; Obeid, Karam M. (Clinical Transplantation, 2023)
Introduction Noroviral infection can lead to chronic diarrhea in solid organ transplant (SOT) recipients with significant morbidity and mortality. Existing literature has described a wide spectrum of illness and has not come to a consensus on the optimal management of this condition. Methods We undertook a retrospective review of all adult SOT recipients between 1/1/2018 and 12/31/2020 who were diagnosed with their first episode of noroviral diarrhea (NVD). Demographic, clinical interventions, and outcomes within 6 months of diagnosis were recorded. Patients’ outcomes were classified as either resolved, improved or persistent at 6 months. Results Seventy‐nine SOT recipients were included. Thirty‐eight patients (48%) had chronic diarrhea at baseline (CDB). Thirty‐two patients (40%) received nitazoxanide, 28 patients (35%) had their immunosuppression adjusted and seven patients (9%) received intravenous immunoglobulin. Diarrhea improved or resolved in 68 patients (85%). Improvement or resolution of diarrhea was observed in 98% of those who did not have history of chronic diarrhea versus 74% in those who did (p = .002). NVD improved in all 12 patients who had mycophenolate discontinued, although this was not statistically significant (p = .131). Conclusion CDB was associated with worse outcomes regardless of intervention. A low threshold to test for NVD in SOT recipients with chronic diarrhea is prudent to prevent delayed diagnosis.

Invasive Aspergillosis after Renal Transplantation - Sigera, Liyanage Shamithra Madhumali; Denning, David W. (Journal of Fungi, 2023)
Over 95,000 renal transplantation procedures were completed in 2021. Invasive aspergillosis (IA) affects about 1 in 250 to 1 in 43 renal transplant recipients. About 50% of cases occur in the first 6 months after transplantation; the median time of onset is nearly 3 years. Major risk factors for IA include old age, diabetes mellitus (especially if prior diabetic nephropathy), delayed graft function, acute graft rejection, chronic obstructive pulmonary disease, cytomegalovirus disease, and neutropenia. Hospital construction, demolition activities, and residential refurbishments also increase the risk. Parenchymal pulmonary infection is the most common (~75%), and bronchial, sinus, cerebral, and disseminated disease are less common. Typical pulmonary features of fever, dyspnea, cough, and hemoptysis are seen in most patients, but 20% have non-specific general features of illness. Non-specific infiltrates and pulmonary nodules are the commonest radiological features, with bilateral disease carrying a worse prognosis. Bronchoscopy for direct microscopy, fungal culture, and Aspergillus antigen are the fastest means of establishing the diagnosis; a positive serum Aspergillus antigen presages a worse outcome. Standard therapy includes voriconazole, isavuconazole, or posaconazole, with great attention necessary to assess likely drug–drug interactions. Liposomal amphotericin B and echinocandins are less effective. A reduction in or stopping immunosuppression needs careful consideration, given the overall mortality of IA in renal-transplanted patients; continuing corticosteroid after the diagnosis of IA increases mortality by 2.5 times. Surgical resection or the addition of a gamma interferon should also be considered.
Keywords: antifungals; immunosuppression; invasive aspergillosis; renal transplantation

Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants - Schuster, Jennifer E.; Hamdan, Lubna; Dulek, Daniel E.; Kitko, Carrie L.; Batarseh, Einas; Haddadin, Zaid; Stewart, Laura S.; Stahl, Anna; Potter, Molly; Rahman, Herdi; Kalams, Spyros A.; Coffin, Susan; et al. (New England Journal of Medicine, 2023)

High Dose Cefepime Versus Carbapenems for Bacteremia Caused by Enterobacterales with Moderate to High Risk of Clinically Significant AmpC β-lactamase Production - Kunz Coyne, Ashlan J; El Ghali, Amer; Lucas, Kristen; Witucki, Paige; Rebold, Nicholas; Holger, Dana J; Veve, Michael P; Rybak, Michael J (Open Forum Infectious Diseases, 2023)
Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns.Retrospective cohort study of hospitalized patients with E. cloacae, K. aerogenes or C. freundii bacteremia from January 2015 to March 2022 receiving high dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting (IPTW) and time-varying covariates.Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared to carbapenem therapy (adjusted hazard ratio [aHR] 1.45; 95% confidence interval [CI] 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR 1.19; 95% CI 0.52-1.77). Multivariable weighted Cox models identified Pitt Bacteremia score >4 (aHR 1.41; 95% CI 1.04-1.92), deep infection (aHR 2.27; 95% CI 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR 1.32; 95% CI 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged infusion β-lactam was protective (aHR 0.67; 95% CI 0.40-0.89).Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high dose cefepime or a carbapenem as definitive β-lactam therapy.

Nanopore-Targeted Sequencing Improves the Diagnosis and Treatment of Patients with Serious Infections - Zhang, Yi; Lu, Xuan; Tang, Liang V.; Xia, Linghui; Hu, Yu (mBio, 2023)
Serious infections are characterized by rapid progression, poor prognosis, and difficulty in diagnosis. Recently, a new technique known as nanopore-targeted sequencing (NTS) was developed that facilitates the rapid and accurate detection of pathogenic microorganisms and is extremely suitable for patients with serious infections. The aim of our study was to evaluate the clinical application of NTS in the diagnosis and treatment of patients with serious infections. We developed an NTS technology that could detect microorganisms within a 6-h window based on the amplification of the 16S rRNA gene of bacteria, the internal transcribed spacer region of fungi, and the rpoB gene of Mycobacterium. The NTS detection results were compared with those of blood cultures and anal swabs from 50 patients with blood diseases suffering serious infections. The patient’s condition before and after NTS was compared. The response rate and the infection-related mortality after the adjustment of antibiotics based on NTS were calculated. The positivity rate of pathogens was highest in NTS (90%), followed by blood culture (32.6%) and anal swabs (14.6%). After adjusting antibiotics for bacteria and fungi detected by NTS, the patients’ condition improved significantly. Moreover, the response rate of anti-infective treatment based on NTS was 93.02% (40/43), and infection-related mortality was reduced to 0. NTS is an effective method to identify pathogens in the blood specimens of patients with serious infections and can guide anti-infection treatment and reduce infection-related mortality. IMPORTANCE We introduce the application of NTS in blood samples of patients with serious infections and expound the efficiency and accuracy of NTS in detecting pathogenic microorganisms. Our work builds on the considerable interest of the scientific community in the management of serious infection. This issue is becoming more pressing, especially since the incidence of blood diseases is increasing year by year and hematopoietic stem cell transplantation (HSCT) has been widely used in benign and malignant blood diseases in recent years. The infection progression of these patients is faster, and the study further demonstrates the effectiveness of NTS in guiding the diagnosis and treatment of patients with severe infections. We firmly believe that this method will guide clinicians to adjust anti-infection strategies and bring significant benefits to patients, and our study will have implications for the future clinical application of NTS in all kinds of patients with serious infections.
Publisher: American Society for Microbiology

American Society for Transplantation and Cellular Therapy Series: #6 - Management of Invasive Candidiasis in Hematopoietic Cell Transplant Recipients - Neofytos, Dionysios; Steinbach, William J.; Hanson, Kimberly; Carpenter, Paul A.; Papanicolaou, Genovefa A.; Slavin, Monica A. (Transplantation and Cellular Therapy, 2023)
The Practice Guidelines Committee of the American Society of 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 sixth guideline in the series focuses on invasive candidiasis (IC) with FAQs to address epidemiology, clinical diagnosis, prophylaxis and treatment of IC, plus special considerations for pediatric, cord blood, haploidentical and T-cell depleted HCT recipients, CAR-T cell recipients, as well as future research directions.
Keywords: Diagnosis; Epidemiology; Guidelines; Hematopoïetic Cell Transplant; Invasive Candidiasis; Prophylaxis; treatment

Coronavirus Disease 2019 (COVID-19): FAQs for Transplant Candidates, Recipients, and Care Givers - AST (2023)

Enfermedad por Coronavirus 2019 (COVID-19): Preguntas Frecuentes para los Candidatos para Trasplantes, Recibidores y Cuidadores - AST (2023)

Safer Living during COVID-19: Tips for Transplant Patients - Power2Save (2023)

Vida más Segura durante COVID-19 Consejos para Pacientes con Trasplantes - Power2Save (2023)

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis - Senefeld, Jonathon W.; Franchini, Massimo; Mengoli, Carlo; Cruciani, Mario; Zani, Matteo; Gorman, Ellen K.; Focosi, Daniele; Casadevall, Arturo; Joyner, Michael J. (JAMA Network Open, 2023)
Patients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient.To assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion.On August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised.Randomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening.The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled.The prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma.This systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]).These findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.

Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease - Dedrick, Rebekah M; Smith, Bailey E; Cristinziano, Madison; Freeman, Krista G; Jacobs-Sera, Deborah; Belessis, Yvonne; Whitney Brown, A; Cohen, Keira A; Davidson, Rebecca M; Van Duin, David; Gainey, Andrew; Garcia, Cristina Berastegui; et al. (Clinical Infectious Diseases, 2023)
Abstract Background Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

Gaining consensus around patient risk groups and prognostic profiles to guide CMV management among patients with solid organ transplant: insights from a Delphi panel with SOT experts - Pednekar, Priti; Graf, Marlon; Tuly, Rifat; Batt, Katharine; Wang, Connie (Clinical Transplantation, 2023)
Introduction: This study aimed to characterize patient risk groups and respective prognostic profiles to optimize clinical decision-making and guide appropriate medical CMV management among patients with solid organ transplant (SOT). Methods: Between 9/2021 and 2/2022, a 3-round modified Delphi study was conducted to generate consensus among 14 international experts in virology and organ transplantation. Experts were asked about treatment and prognoses for patients in 7 distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/posttransplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top 2 options and ≥75% of experts were within 1 standard deviation of the mean rank. Results: Experts agreed on several unmet needs in CMV disease management postSOT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and emergence of both primary refractory and drug resistant treatment failures. Experts considered CMV viral load, resistance profile and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed lack of long-term use data, concerns over potential resistance, high cost and limited availability as challenges restricting adoption and successful patient management. Conclusion: Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in SOT patients, but additional experiences with newer anti-CMV agents are needed to re-validate expert consensus and update post-transplant CMV guidelines.

Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021 - Ali, Saad Emhmed; Vutien, Philip; Bonham, C. Andrew; Landis, Charles; Kwo, Paul; Esquivel, Carlos; Nguyen, Mindie H. (Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2023)
The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.
Keywords: End Stage Liver Disease; Graft Survival; Hepatitis B; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Liver Transplantation; Retrospective Studies; Severity of Illness Index; Tissue Donors; United States

Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis - Banc-Husu, Anna M.; Moulton, Elizabeth A.; Shiau, Henry; Sanchez, Luz Helena Gutierrez; Desai, Moreshwar S.; Cerminara, Dana; Munoz, Flor M.; Buffaloe, Leanne M.; Valencia-Deray, Kristen G.; Galvan, N. Thao N.; Bhatnagar, Julu; Estetter, Lindsey; et al. (American Journal of Transplantation, 2023)
Publisher: Elsevier
Keywords: CDC; CMV; CRRT; Centers for disease control and prevention; Continuous renal replacement therapy; Cytomegalovirus; DNAnemia; EBV; ELS; EM; Electron microscopy; Epstein-Barr virus; Extracorporeal liver support; FFPE; Formalin-fixed paraffin-embedded; HAdV; HAdV41; HD; HE; HLH; HSV; Hemophagocytic lymphohistiocytosis; Hepatic encephalopathy; Herpes simplex virus; Hospital day; Human adenovirus; Human adenovirus type 41; IDPB; IHC; INR; IS; Immunohistochemistry; Immunosuppression; Infectious disease; Infectious diseases pathology branch; International normalized ratio; LT; Liver transplantation; Liver transplantation/hepatology; PALF; PCR; PID; POD; Pediatric acute liver failure; Pediatrics; Polymerase chain reaction; Postoperative day; Primary immunodeficiency; Quantitative polymerase chain reaction; Soluble interleukin 2 receptor α; XXX; qPCR; sIL2Rα

Donor heart selection: Evidence-based guidelines for providers - Copeland, Hannah; Knezevic, Ivan; Baran, David A.; Rao, Vivek; Pham, Michael; Gustafsson, Finn; Pinney, Sean; Lima, Brian; Masetti, Marco; Ciarka, Agnieszka; Rajagopalan, Navin; Torres, Adriana; et al. (The Journal of Heart and Lung Transplantation, 2023)
Publisher: Elsevier
Keywords: ACAOS; ACC; American College of Cardiologists; B-type natriuretic peptide; BMI; BNP; CABG; CAD; CAV; CNS; CO; COVID-19; CPR; CT; ECG; ECMO; HIV; HLA; INH; INTERMACS; ISHLT; International Society for Heart and Lung Transplantation; LV; LVEF; LVH; MRI; N-terminal prohormone of B-type natriuretic peptide; NT-proBNP; OPO; OPTN; PCI; PGD; PLSVC; SARS-CoV-2; TTE; UNOS; VA; VAD; VV; WHO; World Health Organization; anomalous origination of a coronary artery from the opposite sinus; body mass index; brain death; carbon monoxide; cardiac allograft vasculopathy; cardiopulmonary resuscitation; central nervous system; computed tomography; coronary artery bypass graft; coronary artery disease; coronavirus disease 2019; donor heart; donor risk factors; electrocardiogram; extracorporeal membrane oxygenation; heart transplant; human immunodeficiency virus; human leukocyte antigens; interagency registry for mechanically assisted circulatory support; isonicotinic acid hydrazide; left ventricle; left ventricular ejection fraction; left ventricular hypertrophy; magnetic resonance imaging; organ procurement and transplantation network; organ procurement organization; pHM; percutaneous coronary intervention; persistent left superior vena cava; predicted heart mass; primary graft dysfunction; selection; severe acute respiratory syndrome coronavirus 2; transthoracic echocardiography; united network for organ sharing; veno-arterial; veno-venous; ventricular assist device

Transfer of Extended Spectrum Cephalosporin Resistant Enterobacteriaceae Among Patients on an HSCT Unit and the Value of Surveillance and Contact Isolation - Ford, Clyde D.; Hunter, Bradley D.; Lopansri, Bert K.; Coombs, Jana; Fernley, Tasha; Asch, Julie; Hoda, Daanish (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2023)
Publisher: Elsevier
Keywords: Antibiotic resistance; Colonization; Contact isolation; Enterobacteriaceae; Hematopoietic stem cell transplantation; Surveillance

Short Course of Antifungal Therapy in Patients With Uncomplicated Candida Bloodstream Infection: Another Case of Less Is More in the Clinical Setting? - Vena, Antonio; Bovis, Francesca; Tutino, Stefania; Santagostino Barbone, Alessandro; Mezzogori, Laura; Ponzano, Marta; Taramasso, Lucia; Baldi, Federico; Dettori, Silvia; Labate, Laura; Russo, Chiara; Giacobbe, Daniele Roberto; et al. (Open Forum Infectious Diseases, 2023)
The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs).All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5–11 days) or PC (12–24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method.A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7–11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14–16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P = .02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P = .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31–1.47; P = .20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20–5.80; P = .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35–1.50; P = .38) did not differ between groups.Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.

Bloodstream infections in allogeneic haematopoietic cell recipients from the Swiss Transplant Cohort Study: trends of causative pathogens and resistance rates - Sava, Mihaela; Bättig, Veronika; Gerull, Sabine; Passweg, Jakob R.; Khanna, Nina; Garzoni, Christian; Gerber, Bernhard; Mueller, Nicolas J.; Schanz, Urs; Berger, Christoph; Chalandon, Yves; van Delden, Christian; et al. (Bone Marrow Transplantation, 2023)
Number: 1 Publisher: Nature Publishing Group
Keywords: Haematological cancer; Health care

Lung Transplantation for COVID-19–related Lung Disease: Clinical Experience and Call for a Global Registry - Weder, Max M.; Aslam, Saima; Ison, Michael G. (Transplantation, 2023)
An abstract is unavailable.

Letter to the editor: “hook” (prozone) effect in sars‐cov‐2 anti‐spike binding antibody levels following vaccination, infection, or monoclonal antibody in solid organ transplant recipients - Abedon, Aura T.; Chiang, Teresa P. Y.; Karaba, Andrew H.; Alejo, Jennifer L.; Chahoud, Margaret; Hussey, Casey; Lopes, Jessica F.; Hussain, Sarah; Larsen, Christian P.; Durand, Christine M.; Heeger, Peter S.; Segev, Dorry L.; et al. (Clinical Transplantation, 2023)

Guidelines for the management of Toxoplasma gondii infection and disease in patients with haematological malignancies and after haematopoietic stem-cell transplantation: guidelines from the 9th European Conference on Infections in Leukaemia, 2022 - Aerts, Robina; Mehra, Varun; Groll, Andreas H; Martino, Rodrigo; Lagrou, Katrien; Robin, Christine; Perruccio, Katia; Blijlevens, Nicole; Nucci, Marcio; Slavin, Monica; Bretagne, Stéphane; Cordonnier, Catherine (The Lancet Infectious Diseases, 2023)

Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study - Aleyadeh, Wesam; Verna, Elizabeth C.; Elbeshbeshy, Hany; Sulkowski, Mark S.; Smith, Coleman; Darling, Jama; Sterling, Richard K.; Muir, Andrew; Akushevich, Lucy; La, Danie; Terrault, Norah; Fried, Michael W.; et al. (American Journal of Transplantation, 2023)

An analysis of the outcomes of Clostridioides difficile occurring in intestinal transplant recipients requiring hospitalization - Amjad, Waseem; Schiano, Thomas; Segovia, Maria C.; Malik, Adnan; Weiner, Joshua; Horslen, Simon; Jafri, Syed-Mohammed (Transplant Infectious Disease, 2023)
Background Organ transplantation is a known risk factor for Clostridioides difficile infection (CDI). There is limited published data on the impact of CDI in the intestinal transplant population. Methods We utilized the National Readmission Database (2010–2017) to study the outcomes of CDI in patients having a history of intestinal transplantation. Association of CDI with readmission and hospital resource utilization was computed in multivariable models adjusted for demographics and comorbidities. Results During 2010–2017, 8442 hospitalizations with the history of intestinal transplantation had indexed hospital admissions. Of these, 320 (3.8%) had CDI. CDI hospitalization in intestine transplant patients was associated with higher median cost \54 430 (IQR: 27 231, 109 980) as compared to patients who did not have CDI \48 888 (IQR: 22 578, 112 777), (β: 71 814 95% confidence intervals [CI]: 676–142 953, p = .048). The median length of stay was also longer for patients with CDI 7 (IQR: 4, 13) days as compared to 5 (IQR: 3, 11) days in non-CDI (β: 5.51 95% CI: 0.73–10.29, p = .02). The mortality rate, intestinal transplant complications, presence of malnutrition, acute kidney injury, ICU admissions, and sepsis were similar in both groups. CDI was the top cause of 30-day readmission in the intestinal transplant recipients with CDI during the index admission; the number of 30-day readmissions also increased from 2010 to 2017. Conclusion CDI hospitalization in post–intestine transplant patients occurs commonly and is associated with a longer length of stay and higher costs during hospitalization. The CDI was the most common cause of readmission after the index admission of CDI in these patients.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.13951
Keywords: 30-day hospital readmissions; Clostridioides difficile infection; intestinal transplant recipients

Clinical Outcomes and Risk Factors for Carbapenem-resistant Enterobacterales Bloodstream Infection in Solid Organ Transplant Recipients - Anesi, Judith A.; Lautenbach, Ebbing; Thom, Kerri A.; Tamma, Pranita D.; Blumberg, Emily A.; Alby, Kevin; Bilker, Warren B.; Werzen, Alissa; Ammazzalorso, Alyssa; Tolomeo, Pam; Omorogbe, Jacqueline; Pineles, Lisa; et al. (Transplantation, 2023)
Background. The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. Methods. A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI. Results. Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001)‚ liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012)‚ lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009)‚ and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months. Conclusions. CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients.

A Diagnostic Approach to Fungal Pneumonia - Azar, Marwan.M. (CHEST, 2023)

Immunization of Solid Organ Transplant Candidates and Recipients - Bahakel, Hannah; Feldman, Amy G.; Danziger-Isakov, Lara (Infectious Disease Clinics of North America, 2023)

Role of cytomegalovirus specific cell-mediated immunity in the monitoring of cytomegalovirus infection among living donor liver transplantation adult recipients: A single-center experience - Bhugra, Arjun; Khodare, Arvind; Agarwal, Reshu; Pamecha, Viniyendra; Gupta, Ekta (Transplant Infectious Disease, 2023)
Background Cytomegalovirus (CMV) is one of the most common post-transplant viral infections causing significant morbidity and occasional mortality. Limited literature on the potential role of pre-transplant CMV-specific cell-mediated immunity (CMV-CMI) is available. This study aimed to evaluate the clinical utility of pre-transplant CMV-CMI monitoring in the occurrence of post-transplant CMV infection. Methods This was a prospective, observational study where all adult CMV seropositive patients undergoing living donor liver transplantation at a tertiary care institute were enrolled. CMV-CMI was measured using QuantiFERON-CMV (Qiagen GmbH, Hilden, Germany) and interpreted as positive if the value was ≥0.2 IU/ml, 1–2 days prior to the transplant. Based on pre-transplant CMV-CMI, cases were classified into Group 1 (n = 13, 43.3%) (positive) and Group 2 (n = 17, 56.7%) (negative). CMV infection was defined as the detection of CMV-DNA > 2.7 log10 IU/ml in plasma specimens. Results The mean age was 43 years with male (n = 29, 96.9%) predominance. Overall 40% of recipients developed post-transplant CMV infection, two (15.4%) in group 1 and 10 (58.8%) in group 2 (p-value = 0.016). Recipients in group 2 had 87% higher odds (odds ratio 0.13, confidence interval [CI] 95) of developing post-transplant CMV infection compared to group 1. The overall median duration of occurrence of post-transplant CMV infection was 26 days with the median viral load being 2.8 log10 IU/ml. The treatment duration was 13 days in group 1 and 28 days in group 2 (p = 0.003). Group 1 recipients showed rapid clearance of CMV-DNA within 7 days compared to group 2 in which it was 21 days (p = 0.004, CI 95). Conclusion Pre-transplant CMV-CMI may play a protective role against post-transplant CMV infection and can serve as an adjunct for pre-transplant risk stratification.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14011
Keywords: CMV-CMI; CMV-QuantiFERON; infections; post-transplant

Clinical outcomes of ventricular assist device support by HIV infection status: An STS-INTERMACS analysis - Birk, Sarah E.; Baran, David A.; Campbell, Robert; Herre, John M.; Sadatsafavi, Hessam; Yehya, Amin (The Journal of Heart and Lung Transplantation, 2023)
BACKGROUND: Cardiovascular disease remains the leading cause of mortality in human im munodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely of fered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. METHODS: We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. RESULTS: Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p = 0.02), had lower body mass index (26 kg/m2 vs 29 kg/ m2, p = 0.001), and had higher rates of prior stroke (8% vs 4%, p = 0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. CONCLUSIONS: With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure.

How I approach diarrhea in hematological transplant patients: A practical tool - Castillo Almeida, Natalia E.; Cichon, Catherine J.; Gomez, Carlos A. (Transplant Infectious Disease, 2023)
Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14184
Keywords: CMV; Clostridioides difficile; acute graft-versus-host disease (aGvHD); diarrhea; gastrointestinal panel; hematopoietic stem-cell transplantation; multiplex; syndromic

Adenovirus infection in allogeneic hematopoietic cell transplantation - Cesaro, Simone (Transplant Infectious Disease, 2023)
Adenovirus (AdV) infection occurs in 0–20% of patients in the first 3–4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end-organ damage, and 6-month overall mortality. The main risk factors for AdV infection are T-cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III–IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109/L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre-emptive start of cidofovir as viral load exceeds the threshold of ≥102–3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus-specific T-cell immunity in the first few months post-HCT by the administration of donor-derived or third-party-donor-derived virusspecific T-cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.

Update of recommendations for the management of COVID-19 in patients with haematological malignancies, haematopoietic cell transplantation and CAR T therapy, from the 2022 European Conference on Infections in Leukaemia (ECIL 9) - Cesaro, Simone; Mikulska, Malgorzata; Hirsch, Hans H.; Styczynski, Jan; Meylan, Sylvain; Cordonnier, Catherine; Navarro, Davide; von Lilienfeld-Toal, Marie; Mehra, Varun; Marchesi, Francesco; Besson, Caroline; Masculano, Raul Cordoba; et al. (Leukemia, 2023)

Pneumocystis jirovecii Infection in autologous hematopoietic stem cell transplant recipients - Coda, John; Raser, Kadee; Anand, Sarah M.; Ghosh, Monalisa; Gregg, Kevin; Li, Jinju; Maciejewski, John J.; Pawarode, Attaphol; Riwes, Mary M.; Tillman, Christina; Polk, Avery; Kandarpa, Malathi; et al. (Bone Marrow Transplantation, 2023)

Improving Diagnosis of Pulmonary Mucormycosis - Coste, Anne; Conrad, Anne; Porcher, Raphaël; Poirée, Sylvain; Peterlin, Pierre; Defrance, Claire; Letscher-Bru, Valérie; Morio, Florent; Gastinne, Thomas; Bougnoux, Marie-Elisabeth; Suarez, Felipe; Nevez, Gilles; et al. (CHEST, 2023)

Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients - Demirhan, Salih; Munoz, Flor M.; Valencia Deray, Kristen G.; Bocchini, Claire E.; Danziger-Isakov, Lara; Blum, Samantha; Sharma, Tanvi S.; Sherman, Gilad; Boguniewicz, Juri; Bacon, Samantha; Ardura, Monica I.; Maron, Gabriela M.; et al. (American Journal of Transplantation, 2023)

Updates in Cytomegalovirus Prevention and Treatment in Solid Organ Transplantation - Doss, Kathleen M.; Heldman, Madeleine R.; Limaye, Ajit P. (Infectious Disease Clinics of North America, 2023)

Real-world effectiveness of preemptive therapy (PET) for cytomegalovirus (CMV) disease prevention in CMV high-risk donor seropositive/recipient seronegative (D+R-) liver transplant recipients (LTxR) - Doss, Kathleen M.; Kling, Catherine E.; Heldman, Madeleine R.; Singh, Nina; Wagener, Marilyn; Rakita, Robert M.; Fisher, Cynthia E.; Limaye, Ajit P. (Transplant Infectious Disease, 2023)
Background Despite superiority of preemptive therapy (PET) compared to universal prophylaxis for prevention of cytomegalovirus (CMV) disease in the CAPSIL randomized trial among CMV D+R- liver transplant recipients (LTxRs), real-world effectiveness may be lower because of logistical concerns about feasibility of PET. Methods We retrospectively assessed PET as standard clinical care at a single transplant center among 50 consecutive adult CMV D+R- LTxRs undergoing a first liver transplant between 4/4/2019 and 5/18/2021 and compared outcomes and adherence to those randomized to PET in the CAPSIL study (N = 100). The primary outcome was CMV disease and secondary outcomes were biopsy-confirmed acute allograft rejection, retransplant, invasive fungal infections, and death, all assessed by 1-year post-transplant. Exploratory outcomes included virologic parameters and measures of adherence to protocol-specified CMV qPCR monitoring. Results Baseline characteristics were similar between groups. The cumulative incidence of CMV disease at 1-year post-transplant was 4/50 (8%) versus 9/100 (9%) in the real-world and CAPSIL cohorts, respectively, p = 1.0. The rate of breakthrough CMV disease during the 100-day PET period was low (2/50 [4%]) and similar to the PET cohort from the CAPSIL study (3/100 [3%]). All secondary and exploratory outcomes were not significantly different between the real-world and CAPSIL PET cohorts. Conclusions In this first reported study of real-world PET, the feasibility and effectiveness for CMV disease prevention and for other clinical outcomes in CMV D+R- LTxRs were similar to those reported with PET in a clinical trial. Additional studies to confirm feasibility and generalizability in other settings are warranted.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14015
Keywords: CMV; preemptive therapy (PET); solid organ transplantation (SOT)

Effective CMV prophylaxis with high-dose valaciclovir in allogeneic hematopoietic stem-cell recipients at a high risk of CMV infection - Douglas, Genevieve; Yong, Michelle K.; Tio, Shio Yen; Chau, Maggie; Prabahran, Ashvind; Sasadeusz, Joe; Slavin, Monica; Ritchie, David; Chee, Lynette (Transplant Infectious Disease, 2023)
Background Cytomegalovirus (CMV) infection increases mortality and morbidity following allogeneic hematopoietic stem-cell transplantation (alloHSCT). Universal antiviral prophylaxis with letermovir is effective but unsubsidized in Australia. Valaciclovir demonstrates anti-CMV activity in high doses, but few current real-world studies explore its use as primary prophylaxis in high-risk patients post-alloHSCT. Methods We performed a retrospective analysis of alloHSCT recipients at high risk of clinically significant CMV infection (cs-CMVi), defined as a plasma CMV DNA viral load of >400 IU/ml requiring preemptive therapy, or CMV disease. High-risk recipients were CMV seropositive and underwent T-cell depleted, haploidentical or umbilical cord stem-cell transplants. Consecutive patients transplanted from July 2018 to January 2020, treated with valaciclovir 2 g TDS from day +7 to +100 (HD-VALA), were compared to a historical cohort (July 2017–June 2018) who only received preemptive CMV therapy, and standard valaciclovir (SD-VALA) for varicella/herpes prophylaxis. We compared incidence of and time to cs-CMVi. Results In the SD-VALA cohort (n = 27, median CMV follow-up duration 259 days), 23/27 (85%) developed cs-CMVi at a median of 39 days. For the HD-VALA cohort (n = 35, median CMV follow-up duration 216 days), 19/35 (54%) developed cs-CMVi, at a median of 68 days. Time to cs-CMVi was significantly longer in HD-VALA cohort (p < .0001). On multivariate analysis, HD VALA reduced the risk of cs-CMVi (HR 0.32, p = .0005). Conclusions In alloHSCT recipients at high risk for cs-CMVi, HD-VALA resulted in lower cumulative reactivation, and delayed reactivation, reducing requirement for preemptive CMV therapy in the early post-engraftment period.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.13994
Keywords: Bone Marrow Transplant; CMV; Prophylaxis; Valaciclovir; bone marrow transplant; prophylaxis; valaciclovir

Update on Epidemiology and Outcomes of Infection in Pediatric Organ Transplant Recipients - Dulek, Daniel E. (Infectious Disease Clinics of North America, 2023)

Updates in Molecular Diagnostics in Solid Organ Transplantation Recipients - Everhart, James; Henshaw, Nancy G. (Infectious Disease Clinics of North America, 2023)

Serologic follow-up of solid organ transplant recipients who received organs from donors with reactive syphilis tests: A retrospective cohort study - Fernández García, Oscar A.; Singh, Ameeta E.; Gratrix, Jennifer; Smyczek, Petra; Doucette, Karen (Clinical Transplantation, 2023)
The increased procurement of organs from donors with risk factors for blood-borne diseases and the expanding syphilis epidemic have resulted in a growing number of organs transplanted from donors with reactive syphilis serology in our center. Based on guidelines, recipients typically receive therapy shortly after the transplant, but data on outcomes are limited. The primary objective of this study was to determine syphilis seroconversion rates at three months post-transplant in recipients of solid organs procured from donors with reactive syphilis serology. Organ donors and recipients were tested for syphilis antibody; positive results were confirmed with Treponema pallidum Particle Agglutination (TPPA). Eleven donors with reactive syphilis antibody donated organs to 25 syphilis negative recipients. Three recipients seroconverted at post-transplant month 3. All of them had received therapy shortly after transplant. TPPA was negative in all 3. Despite post-transplant treatment, 3 of 25 (12%) syphilis negative recipients of organs from syphilis positive donors seroconverted at 3 months. All remained TPPA negative possibly reflecting passive antibody transfer or differing test sensitivity to low level treponemal antibodies. Further studies are needed to assess optimal syphilis transmission prevention strategies and follow up recipient testing in organ transplantation.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/ctr.14896
Keywords: bacterial donors and donation; donor-derived infections; donors and donation; infection and infectious agents

Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice - Fernández-Ruiz, Mario; Bodro, Marta; Gutiérrez Martín, Isabel; Rodriguez-Álvarez, Regino; Ruiz-Ruigómez, María; Sabé, Núria; López-Viñau, Teresa; Valerio, Maricela; Illaro, Aitziber; Fortún, Jesús; Salto-Alejandre, Sonsoles; Cordero, Elisa; et al. (Transplantation, 2023)

Recipient and kidney graft outcomes of deceased donors with human immunodeficiency virus in the United States - Fontana, Lauren; Swanson, Kurtis J; El-Rifai, Rasha; Bregman, Adam; Spong, Richard; Kirchner, Varvara A.; Pruett, Timothy; Jackson, Scott; Riad, Samy (Transplant Infectious Disease, 2023)
Background The HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long-term outcomes of recipients with HIV by donor HIV testing status. Methods Using the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV-positive between 1/1/16-12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab−/NAT− (n = 810), Donor Ab+ /NAT− (n = 98), and Donor Ab+/NAT+ (n = 90). We compared recipient and death-censored graft survival (DCGS) by donor HIV testing status using Kaplan–Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1-year outcomes: acute rejection, re-hospitalization, and serum creatinine. Results In Kaplan–Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p = .667; log rank p = .388). DGF occurred more frequently in donors with HIV Ab−/NAT− testing compared with Ab+/NAT− or Ab+/NAT+ testing (38.0% vs. 28.6% vs. 26.7%, p = .028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab−/NAT− testing (p < .001). Acute rejection, re-hospitalization and serum creatinine at 12 months did not differ between the groups. Conclusions Patient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT− or Ab+/NAT+ testing shortens dialysis time prior to transplant.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14093
Keywords: HIV; disease recurrence; glomerulonephritis; living related donor; long-term outcomes

The cascade of care in testing and treatment of latent tuberculosis infection in liver transplant candidates - Foppiano Palacios, Carlo; Medvedeva, Natalia; Cheung, Harry; Cohen, Elizabeth; Azar, Marwan M.; Malinis, Maricar (Transplant Infectious Disease, 2023)
Background Testing and treatment for latent tuberculosis infection (LTBI) can mitigate risk of active tuberculosis (TB) post-liver transplant (LT). Testing and treatment completion rates have been reported low in this population. Our study aims to quantify the proportion of LT candidates who completed LTBI care cascade in our center. Methods A retrospective chart review was conducted on LT candidates from 2012 to 2021. Primary outcome was the proportion of patients who completed each cascade stage. Secondary outcome was an analysis of factors associated with positive and indeterminate LTBI testing. Results Of the 273 LT candidates, 265 (97.1%) were referred to transplant infectious disease (TID), 264 (96.7%) had orders for interferon-gamma release assay (IGRA), 262 (96%) underwent TID evaluation, and 259 (94.9%) completed IGRA. Twenty had LTBI, and 18 were treatment naïve and recommended for treatment. Of the 18, 15 (83.3%) agreed to therapy, 14 (77.8%) initiated treatment, and 12 (66.7%) completed treatment. No posttransplant TB reactivation occurred. Patients born in Asia, previous incarceration, past military service, and granuloma findings on chest imaging were likely to have positive IGRA (p < .05). Older age and travel to TB-endemic countries were likely to have indeterminate IGRA (p < .05). Indeterminate IGRAs were more common in QuantiFERON (QTF)-Gold Plus TB (15.3%) versus QTF-Gold TB (9.3%, p < .001). Conclusions High rates of LTBI testing and treatment initiation and completion can be attributed to a standardized process that includes TID evaluation. Future studies in larger cohort are needed to better understand factors that can optimize the completion rates of LTBI treatment in LT candidates.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.13999
Keywords: latent tuberculosis; liver transplant candidates; pre-transplant evaluation

Emerging Diagnostics and Therapeutics for Invasive Fungal Infections - Friedman, Daniel Z.P.; Schwartz, Ilan S. (Infectious Disease Clinics of North America, 2023)

Balancing the Risks and Benefits of Pet Ownership in Pediatric Transplant Recipients - García Sánchez, Paula; Iglesias, Irene; Falces-Romero, Iker; Serrano-Villar, María; Calvo, Cristina; Alcolea, Sonia; Sainz, Talía; Mendez-Echevarría, Ana (Transplantation, 2023)
In recent decades, the number of pediatric transplantations and their survival rates have increased. Psychological problems and poorer quality of life are notable among children undergoing transplantation and can have long-lasting consequences and affect immunosuppressive therapy adherence. Pet ownership and animal contact have been associated with physical, mental, and social health benefits. Despite these potential benefits, however, companion animals are known to be a source of infection, which is one of the main concerns for clinicians. Because of immunosuppression, these children are particularly vulnerable to infections. Zoonoses comprise a long list of infectious diseases and represent a major public health problem. Nevertheless, many families and most healthcare providers are unaware of these potential risks, and there is a worrisome lack of recommendations to manage the risk-benefit balance, which could pose a risk for acquiring a zoonosis. Furthermore, no data are available on the number of transplanted patients with pets, and this risk-benefit balance is difficult to adequately evaluate. In this document, we review the currently available evidence regarding the epidemiology of zoonotic infections in patients undergoing transplantation, focusing on pediatric patients from a risk-benefit perspective, to help inform decision-making for clinicians. Families and healthcare professionals should be aware of the risks, and clinicians should actively screen for pets and offer comprehensive information as part of routine clinical practice. A multidisciplinary approach will ensure proper care of patients and pets and will establish preventive measures to ensure patients are safe living with their pets.

Investigational non-antibiotic therapeutics for infections in hematopoietic cell transplant recipients and patients with hematologic malignancies receiving cellular therapies - Garner, Will; Hamza, Amjad; Haidar, Ghady (Transplant Infectious Disease, 2023)
In the age of progressive antimicrobial resistance and increased difficulty combating infections in immunocompromised hosts, there has been renewed interest in the use of nontraditional therapeutics for infections. Herein, we review the use of investigational non-pharmaceutical anti-infective agents targeting fungal, bacterial, and viral infections in patients with hematologic malignancies, focusing on those receiving hematopoietic cell transplantation or cellular therapies. We discuss immune checkpoint inhibitors, granulocyte transfusions, bone marrow colony-stimulating factors, bacteriophages, fecal microbiota transplantation, and virus specific T-cell therapy. Although there is promising early experience with many of these treatments, further studies will be required to define their optimal role in the therapeutic armamentarium against infections in immunocompromised hosts.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14193
Keywords: bacteriophage therapy; cellular therapy; checkpoint inhibitors; colony-stimulating factor; fecal microbiota transplant; granulocyte transfusion; hematopoietic cell transplant; virus-specific-T-cell therapy

Systemic corticosteroids for outpatient respiratory viral infections in lung transplant recipients - Ghandi, Vardhil; Li, David; Weinkauf, Justin; Lien, Dale; Hirji, Alim; Varughese, Rhea; Weatherald, Jason; Sligl, Wendy; Kabbani, Dima; Schwartz, Ilan; Doucette, Karen; Cervera, Carlos; et al. (Transplant Infectious Disease, 2023)
Introduction: Respiratory viral infections (RVI) in lung transplant recipients (LTR) have variably been associated with rejection and chronic lung allograft dysfunction. Our center has used systemic corticosteroids to treat outpatient RVI in some cases, but evidence is limited. We reviewed all adult LTR diagnosed with outpatient RVI January 2017 to December 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 s [FEV1]) at next stable visit between 1 and 12 months postinfection, expressed as a ratio over stable preinfection FEV1 (FEV1 recovery ratio). Methods: We identified 100 adult LTR with outpatient RVI diagnoses eligible for study, 36% of whom received corticosteroids. We modelled the adjusted association between corticosteroid use and FEV1 recovery ratio using linear regression. Results: Steroid-treated patients had a lower FEV1 presentation ratio (0.92 vs. 1.04, p = .0070) and were more likely to have chronic lung allograft dysfunction at time of infection (25% vs. 5%, p = .0077). Mean FEV1 recovery ratio was 1.02 (SD 0.19) with no association with corticosteroid therapy via multivariable linear regression (p = .5888). Conclusions: Steroid treatment was not associated with FEV1 recovery. This suggests corticosteroids may not have a role in the management of RVI in this population.

Antimicrobial Resistance in Organ Transplant Recipients - Giannella, Maddalena; Rinaldi, Matteo; Viale, Pierluigi (Infectious Disease Clinics of North America, 2023)

Features of cytomegalovirus DNAemia and virus-specific T-cell responses in allogeneic hematopoietic stem-cell transplant recipients during prophylaxis with letermovir - Giménez, Estela; Guerreiro, Manuel; Torres, Ignacio; Aguilar, Cristobal; Albert, Eliseo; Hernández-Boluda, Juan Carlos; Hernani, Rafael; Pérez, Ariadna; Amat, Paula; Piñana, José Luis; Montoro, Juan; Solano, Carlos; et al. (Transplant Infectious Disease, 2023)
Background There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis. Methods Twelve adult CMV-seropositive high-risk recipients (median age, 53 years; 9 males/3 females) undergoing LMV prophylaxis and 13 non-LMV allo-HSCT controls (median age, 58 years; 7 males/6 females) were included. CMV DNAemia in plasma was monitored by real-time polymerase chain reaction. Preemptive antiviral therapy (PET) was administered upon detection of ≥1500 IU/ml. CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T cells were enumerated by flow cytometry around days +30, +60, and +90 after allo-HSCT. Ex vivo experiments assessing of the potential effect of LMV on CMV-specific T-cell expansion in a single CMV-seropositive donor were also conducted. Results Five LMV patients (41.6%) developed CMV DNAemia that cleared spontaneously. Four patients (33.3%) developed CMV DNAemia after LMV cessation, of which two required PET. Nine non-LMV patients (69.2%) developed CMV DNAemia (five required PET). The percentage of LMV and non-LMV patients exhibiting detectable CMV-specific T-cell responses was comparable (7/10 vs. 10/13; p = .71). Nevertheless, median CMV-specific CD4+ and CD8+ T-cell counts were lower in LMV patients by days +60 (p = .006 and .02, respectively) and +90 (p = .08 and .02). Ex vivo, CMV-specific CD8+ T cells expanded to the same level either in the presence (19.8%) or in the absence of LMV (20.6%). Conclusions In our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14021
Keywords: CMV DNAemia; CMV-specific T-cell response; cytomegalovirus (CMV); letermovir; prophylaxis

Persisting dental foci increase the risk for bacterial infections before and after liver transplant - Göbel, Philipp; Forsting, Christiane; Klüners, Alexandra; Knipper, Petra; Manekeller, Steffen; Nattermann, Jacob; Kalff, Jörg C.; Kramer, Franz-Josef; Strassburg, Christian P.; Lutz, Philipp (Clinical Transplantation, 2023)
Background Patients awaiting liver transplant are usually assessed for presence of dental foci to prevent bacterial infection post-transplant, but evidence to support dental examination and treatment is limited. We investigated if treatment of dental foci decreased bacterial infections before and after transplant. Methods Patients transplanted at the university hospital of Bonn were retrospectively assessed for occurrence of bacterial infections before and after transplant according to presence and treatment of dental foci. Results 35/110 patients showed good oral health, 39/110 patients received dental care and 36/110 patients did not receive dental care despite poor oral health. Patients with alcohol-associated liver disease presented with the highest rate of dental foci. Bleeding complications due to oral care occurred in five patients with poor coagulation. After transplant, the number of infections per patient was higher in patients with poor oral health (2.9) compared to patients after dental care (1.9) or with good oral health (1.8) (p = .02), with streptococcal infections being more frequent in patients with poor oral health. Before transplant, bacterial infections, in particular bacteraemia and spontaneous bacterial peritonitis, were also more common in patients with untreated dental foci. Streptococci and Staphylococci were more often detected in patients with dental foci. Dental treatment was associated with a reduction in bacterial infections. Conclusion Presence of dental foci is associated with an increased risk for bacterial infections not only after but also before liver transplant. Dental treatment might be a safe and effective procedure to mitigate this risk.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/ctr.14857
Keywords: bacteraemia; peritonitis; spontaneous

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee - Goldman, Jason D.; Pouch, Stephanie M.; Woolley, Ann E.; Booker, Sarah E.; Jett, Courtney T.; Fox, Cole; Berry, Gerald J.; Dunn, Kelly E.; Ho, Chak-Sum; Kittleson, Michelle; Lee, Dong Heun; Levine, Deborah J.; et al. (Transplant Infectious Disease, 2023)
Background Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. Methods Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT– donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. Results From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT– donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT– donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. Conclusions Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14013
Keywords: COVID-19; SARS-CoV-2; donor; safety; transmission; transplantation; utilization

Strongyloides infection screening in transplant candidates: What is the best strategy? - Gryschek, Ronaldo Cesar Borges; Corral, Marcelo Andreetta; Sitta, Renata Barnabé; Gottardi, Maiara; Pierrotti, Ligia Camera; Costa, Silvia Figueiredo; Abdala, Edson; Chieffi, Pedro Paulo; de Paula, Fabiana Martins (Transplant Infectious Disease, 2023)
Background The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern. Methods In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates. Results By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR). Conclusion The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14153
Keywords: Strongyloides infection; diagnosis methods; transplant candidates

Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug-resistant Burkholderia multivorans - Haidar, Ghady; Chan, Benjamin K.; Cho, Shu-Ting; Hughes Kramer, Kailey; Nordstrom, Hayley R.; Wallace, Nathan R.; Stellfox, Madison E.; Holland, Mische; Kline, Ellen G.; Kozar, Jennifer M.; Kilaru, Silpa D.; Pilewski, Joseph M.; et al. (Transplant Infectious Disease, 2023)
Background There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died. Methods Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis. Results Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O-antigen profiles of an early versus a late isolate. Conclusions This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14041
Keywords: Burkholderia; antibiotic resistance; cystic fibrosis; phage therapy

Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020 - Hosseini-Moghaddam, Seyed M.; Kothari, Sagar; Humar, Atul; Albasata, Hanan; Yetmar, Zachary A.; Razonable, Raymund R.; Neofytos, Dionysios; D’Asaro, Matilde; Boggian, Katia; Hirzel, Cedric; Khanna, Nina; Manuel, Oriol; et al. (American Journal of Transplantation, 2023)
Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P ¼ .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

In vitro susceptibility patterns for rapidly growing nontuberculous mycobacteria in the United States - Hunkins, Joshua-J.; de-Moura, Vinicius-C.-N.; Eddy, Jared-J.; Daley, Charles-L.; Khare, Reeti (Diagnostic Microbiology and Infectious Disease, 2023)
Antimicrobial susceptibility testing for rapidly growing mycobacteria (RGM) is uncommon or only performed in large reference laboratories. Here we developed a cumulative antibiogram for 14 RGM using the largest sample size to date (N = 3860). All RGM showed 82% to 100% susceptibility to amikacin. Mycobacterium abscessus showed low percentages of susceptibility to most antimicrobials; of antimicrobials without interpretations, the minimum inhibitory concentration-90 for clofazimine was low (≤0.5mg/L). All three subspecies had ≤2.6% rrl resistance mutations, however intact erm(41) was detected in 70% to100% of M. abscessus abscessus and bolletii. Mycobacterium chelonae had a similar susceptibility pattern to M. abscessus subsp. massiliense and Mycobacterium immunogenum except that it was susceptible to tobramycin (87%). Mycobacterium fortuitum complex and similar organisms showed higher frequency of susceptibility to ﬂuoroquinolones, beta-lactams, linezolid, and trimethoprim/sulfamethoxazole. Although relatively small published RGM antibiograms showed substantial variance, a comprehensive antibiogram can help inﬂuence treatment and monitoring patterns of resistance.

Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies - Kampouri, Eleftheria; Little, Jessica S.; Rejeski, Kai; Manuel, Oriol; Hammond, Sarah P.; Hill, Joshua A. (Transplant Infectious Disease, 2023)
Background Chimeric antigen receptor (CAR)-T-cell therapies have revolutionized the management of acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and long-term “on-target off-tumor” effects. Methods All of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non-relapse mortality after CAR-T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post-CAR-T-cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B-cell maturation antigen (BCMA) CAR-T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post-infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion. Results Bacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR-T-cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination. Conclusion Risk stratification tools are available and may help distinguish between infectious and non-infectious causes of fever post-infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14157
Keywords: BCMA; CAR-T-cell therapy; CD19; infections; prediction; prevention; risk stratification

Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis - Kampouri, Eleftheria; Zamora, Danniel; Kiem, Erika S.; Liu, Winnie; Ibrahimi, Sarah; Blazevic, Rachel L.; Lovas, Erika A.; Kimball, Louise E.; Huang, Meei-Li; Jerome, Keith R.; Ueda Oshima, Masumi; Mielcarek, Marco; et al. (Clinical Microbiology and Infection, 2023)

Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation - Kitajima, Toshihiro; Rajendran, Luckshi; Lisznyai, Eric; Lu, Mei; Shamaa, Tayseer; Ivanics, Tommy; Yoshida, Atsushi; Claasen, Marco P.A.W.; Abouljoud, Marwan S.; Sapisochin, Gonzalo; Nagai, Shunji (American Journal of Transplantation, 2023)
Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post–liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/μL), mid (500–1000/μL), and high ALC (>1000/μL). Our main analysis used retrospective data (2013–2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P ¼ .001; low vs high: P < .001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/ high groups (9.1% vs 0.8%; P < .001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P ¼ .004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P < .001) and cytomegaloviremia (15.2% vs 6.8%; P ¼ .03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P ¼ .001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.

Minimizing the Risk of Donor-Derived Events and Maximizing Organ Utilization Through Education and Policy Development - La Hoz, Ricardo M. (Infectious Disease Clinics of North America, 2023)

The expanded role of the transplant pharmacist: a 10-year follow-up - Lichvar, Alicia Beth; Chandran, Mary Moss; Cohen, Elizabeth A.; Crowther, Barrett R.; Doligalski, Christina Teeter; Condon Martinez, Amanda J.; Potter, Lisa M.M.; Taber, David J.; Alloway, Rita R. (American Journal of Transplantation, 2023)

Successful restoration of protective immunity against measles, mumps, and rubella following MMR vaccination in adult hematopoietic cell transplant recipients - Lin, Rick Y.; Anderson, Anthony D.; Morris, Michele I.; Raja, Mohammed; Komanduri, Krishna V.; Camargo, Jose F. (Transplant Infectious Disease, 2023)
Background The optimal number of doses as well as the role for measurement of postvaccination titers after measles, mumps, rubella (MMR) vaccination in adult hematopoietic cell transplantation (HCT) recipients remains unknown. Methods In the present study, we assessed humoral immunity against measles, mumps and rubella before and after MMR vaccination in 187 adults who received at least one dose of the MMR vaccine after HCT. Results Among those with baseline titers, posttransplant prevaccination seroprotection rates were 56%, 30%, and 54% for measles, mumps, and rubella, respectively; and significantly lower in allogeneic versus autologous HCT recipients for measles (39% vs. 80%, p = .0001), mumps (22% vs. 41%; p = .02) and rubella (48% vs. 62%, p = .12). Among those who were seronegative at baseline, seroconversion rates after one dose of MMR were 69%, 56%, and 97% for measles, mumps, and rubella, respectively. Seronegative patients after one dose of MMR (i.e., nonresponders) seroconverted for measles and mumps after a second MMR vaccine dose. Conclusion Our findings demonstrate successful restoration of protective immunity against measles, mumps, and rubella after vaccination in adult HCT recipients; one dose of MMR elicited protective titers in the majority of patients, and a second vaccine dose was immunogenic in nonresponders.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14043
Keywords: hematopoietic cell transplant; immunogenicity; measles; mumps; rubella; vaccine

Infection and clinical xenotransplantation: Guidance from the Infectious Disease Community of Practice of the American Society of Transplantation - Mehta, Sapna A.; Saharia, Kapil K.; Nellore, Anoma; Blumberg, Emily A.; Fishman, Jay A. (American Journal of Transplantation, 2023)

COVID-19 Management Strategies in Solid Organ Transplant Recipients - Mendoza, Maria Alejandra; Razonable, Raymund (Infectious Disease Clinics of North America, 2023)

A review of transplant infectious diseases and pediatric transplant infectious diseases curriculum - Morales, Megan K.; Danziger-Isakov, Lara; Nematollahi, Saman (Current Opinion in Organ Transplantation, 2023)
This review of transplant infectious diseases training summarizes growth through the decades, the current landscape of recommend training elements, suggested areas for continued development and expansion in training as well as novel methodologies to reach a modern trainee audience.

Mycobacteria in Organ Transplant Recipients - Narsana, Niyati; Alejandra Pérez, María; Subramanian, Aruna (Infectious Disease Clinics of North America, 2023)

Society of Critical Care Medicine and the Infectious Diseases Society of America Guidelines for Evaluating New Fever in Adult Patients in the ICU - O’Grady, Naomi P.; Alexander, Earnest; Alhazzani, Waleed; Alshamsi, Fayez; Cuellar-Rodriguez, Jennifer; Jefferson, Brian K.; Kalil, Andre C.; Pastores, Stephen M.; Patel, Robin; Van Duin, David; Weber, David J.; Deresinski, Stanley (Critical Care Medicine, 2023)
OBJECTIVES: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. PANEL DESIGN: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline. METHODS: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements. RESULTS: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data. CONCLUSIONS: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue—including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers.

Approach to diagnostic evaluation and prevention of invasive fungal disease in patients prior to allogeneic hematopoietic stem cell transplant - O'Keeffe, Jessica C.; Singh, Nikhil; Slavin, Monica A. (Transplant Infectious Disease, 2023)
In recent years, advancements in the treatment landscape for hematological malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia, have significantly improved disease prognosis and overall survival. However, the treatment landscape is changing and the emergence of targeted oral therapies and immune-based treatments has brought forth new challenges in evaluating and preventing invasive fungal diseases (IFDs). IFD disproportionately affects immunocompromised hosts, particularly those undergoing therapy for acute leukemia and allogeneic hematopoietic stem cell transplant. This review aims to provide a comprehensive overview of the pretransplant workup, identification, and prevention of IFD in patients with hematological malignancy. The pretransplant period offers a critical window to assess each patient’s risk factors and implement appropriate prophylactic measures. Risk assessment includes evaluation of disease, host, prior treatments, and environmental factors, allowing a dynamic evaluation that considers disease progression and treatment course. Diagnostic screening, involving various biomarkers and radiological modalities, plays a crucial role in early detection of IFD. Antifungal prophylaxis choice is based on available evidence as well as individual risk assessment, potential for drug–drug interactions, toxicity, and patient adherence. Therapeutic drug monitoring ensures effective antifungal stewardship and optimal treatment. Patient education and counselling are vital in minimizing environmental exposures to fungal pathogens and promoting medication adherence. A well-structured and individualized approach, encompassing risk assessment, prophylaxis, surveillance, and patient education, is essential for effectively preventing IFD in hematological malignancies, ultimately leading to improved patient outcomes and overall survival.

Cytomegalovirus breakthrough and resistance during letermovir prophylaxis - Perchetti, Garrett A.; Biernacki, Melinda A.; Xie, Hu; Castor, Jared; Joncas-Schronce, Laurel; Ueda Oshima, Masumi; Kim, YoungJun; Jerome, Keith R.; Sandmaier, Brenda M.; Martin, Paul J.; Boeckh, Michael; Greninger, Alexander L.; et al. (Bone Marrow Transplantation, 2023)
Letermovir is a relatively new antiviral for prophylaxis against cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT). CMV-seropositive HCT recipients who received letermovir prophylaxis from 2018 to 2020 at our center were evaluated for letermovir resistance and breakthrough CMV reactivation. Two-hundred twenty-six letermovir recipients were identified and 7/15 (47%) with CMV DNAemia ≥200 IU/mL were successfully genotyped for UL56 resistance. A single C325Y resistance mutation was identified in an umbilical cord blood recipient. Ninety-five (42%), 43 (19%), and 15 (7%) patients had breakthrough CMV at any level, ≥150 IU/mL, and ≥500 IU/mL, respectively. Risk factors for breakthrough CMV reactivation at each viral threshold were examined. Cumulative steroid exposure was the strongest risk factor for CMV at all evaluated viral thresholds. Graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide (aHR 2.34, 95% CI 1.28–4.28, p = 0.001) or calcineurin inhibitors plus mycophenolate (aHR 2.24, 95% CI 1.30–3.86, p = 0.004) were also associated with an increased risk of CMV reactivation at any level. De novo letermovir resistance is rare and can be successfully treated using other antivirals. Letermovir effectively prevents clinically significant CMV, however, subclinical CMV reactivation occurs frequently at our center.
Keywords: Cancer; Clinical genetics; Haematopoietic stem cells; Infectious diseases; Stem-cell research

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year - Permpalung, Nitipong; Liang, Tao; Gopinath, Shilpa; Bazemore, Katrina; Mathew, Joby; Ostrander, Darin; Durand, Christine M.; Shoham, Shmuel; Zhang, Sean X.; Marr, Kieren A.; Avery, Robin K.; Shah, Pali D. (The Journal of Heart and Lung Transplantation, 2023)

High rate of adenovirus detection in gastrointestinal biopsies of symptomatic stem cell transplant recipients - Pikkel‐Geva, Hagar Z.; Grisariu, Sigal; Rivkin, Mila; Stepensky, Polina; Strahilevitz, Jacob; Averbuch, Dina; Orit, Caplan; Even‐Or, Ehud; Zaidman, Irina; Zimran, Eran; Wolf, Dana G.; Avni, Batia (Clinical Transplantation, 2023)
Abstract Objectives The gastrointestinal (GI) tract is a major human adenovirus (HAdV) replication site in patients undergoing hematopoietic stem cell transplantation (HSCT), yet the prevalence and correlates of HAdV GI infection in this setting have remained poorly recognized, especially among adult HSCT recipients. Design or methods We retrospectively studied the prevalence and risk factors of HAdV GI‐tissue infection in HSCT recipients (73 adults and 15 children) with GI symptoms who underwent GI‐tissue biopsy between January‐2012 and December‐2017. The presence of HAdV in the GI tissues was determined by real‐time PCR. Results HAdV GI‐tissue infection was detected in 21 (23.9%) patients, with similar infection rates identified in adults and children. GI‐tissue detection was more common at late (>100 days) compared to early times post‐transplantation (50% vs. 12.9%, p < .001). The presence of bloody diarrhea, Arab ethnicity ( p = .014) and concurrent cytomegalovirus GI‐tissue detection ( p = .025) were significantly correlated with HAdV GI‐tissue infection, while chronic graft versus host disease was of borderline association ( p = .055). Conclusions Our findings reveal a high rate and new clinical‐demographic correlates of HAdV GI‐tissue infection in adult and pediatric HSCT recipients with GI symptoms. The findings highlight the need for future prospective studies to assess the relatedness of HAdV infection to the GI symptoms, and the prevalence, impact, and treatment of HAdV GI infection in HSCT recipients.

Duration of antifungal treatment in mold infection: when is enough? - Portillo, Vera; Neofytos, Dionysios (Current Opinion in Infectious Diseases, 2023)
Decisions to stop antifungal treatment are based on poorly defined treatment responses and immune reconstitution and experts’ opinions. More evidence is needed to determine the optimal duration of treatment of IMI. Well designed, easy to use, and realistic algorithms to help clinicians decide when to stop antifungal treatment are urgently needed.

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients - Rodig, Nancy M.; Weatherly, Madison; Kaplan, Abby L.; Ballal, Sonia Arora; Elisofon, Scott A.; Daly, Kevin P.; Kahn, Stacy A. (Transplantation, 2023)
Background. Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking. Methods. We describe the efficacy and safety of FMT among pediatric SOT recipients in a singlecenter retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4–18 y who received FMT a median of 5.3 y post-SOT. Results. Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss. Conclusions. In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.

Epstein–Barr Viral Load Monitoring Strategy and the Risk for Posttransplant Lymphoproliferative Disease in Adult Liver Transplantation: A Cohort Study - Ruijter, Bastian N.; Wolterbeek, Ron; Hew, Mitchell; Van Reeven, Marjolein; Van Der Helm, Danny; Dubbeld, Jeroen; Tushuizen, Maarten E.; Metselaar, Herold; Vossen, Ann C.T.M.; Van Hoek, Bart (Annals of Internal Medicine, 2023)

Real world experience with Maribavir for the treatment of cytomegalovirus in solid organ transplant recipients - Sabatino, David C.; Hedvat, Jessica; Salerno, David M.; Pereira, Marcus R.; Lange, Nicholas W. (Clinical Transplantation, 2023)
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/ctr.14929
Keywords: cytomegalovirus; maribavir; solid organ transplant

The 2023 International Society for Heart and Lung Transplantation Guidelines for Mechanical Circulatory Support: A 10- Year Update - Saeed, Diyar; Feldman, David; Banayosy, Aly El; Birks, Emma; Blume, Elizabeth; Cowger, Jennifer; Hayward, Christopher; Jorde, Ulrich; Kremer, Jamila; MacGowan, Guy; Maltais, Simon; Maybaum, Simon; et al. (The Journal of Heart and Lung Transplantation, 2023)

Organ Donors with Human Immunodeficiency Virus and Hepatitis C Virus - Salas, Jordan; Storm, Kaitlyn; Durand, Christine M. (Infectious Disease Clinics of North America, 2023)

Absolute Lymphocyte Count as a Marker for Cytomegalovirus Infection After Heart Transplantation - Schoeberl, Armin-Kai; Zuckermann, Andreas; Kaider, Alexandra; Aliabadi-Zuckermann, Arezu; Uyanik-Uenal, Keziban; Laufer, Guenther; Goekler, Johannes (Transplantation, 2023)
Background. Previous studies indicate an association between reduced absolute lymphocyte count (ALC) and cytomegalovirus (CMV) infection after solid organ transplantation and have therefore highlighted the potential of ALC as a simple tool to predict CMV infection in transplant patients. This study aimed to examine the utility of ALC as a valuable marker for CMV infection in heart transplant patients. Methods. Clinical information and ALC data of all adult patients who received orthotopic heart transplantation at the Medical University of Vienna between January 2004 and May 2019 were collected. We performed a multivariable Cox regression model that incorporates repeated measurements of ALC as a time-varying continuous factor in 2 ways, first as continuous logarithmic factor considering a 50% decrease of ALC levels and second as binary factor using a threshold of 610 cells/μL. Results. One hundred fifty-eight (39%) patients developed CMV infection over the course of 2 y. Patients with lymphopenia were shown to be at higher risk of developing CMV infection both in the continuous approach (HR [per 50% reduction] 1.29; confidence interval [CI], 1.09-1.53; P = 0.003) and the binary approach with a cutoff of 610 cells/μL (HR 1.74; CI, 1.20-2.51; P = 0.003). Conclusions. This study demonstrated a strong association between reduced ALC and the development of CMV infection after heart transplantation. ALC value monitoring could provide an additional tool to assess individualized CMV risk after solid organ transplantation.

Incidence of breakthrough fungal infections on isavuconazole prophylaxis compared to posaconazole and voriconazole - Scott, Sara A.; Perry, Cory; Mahmoudjafari, Zahra; Martin, Grace A.; Boyd, Samuel; Thompson, Jeffrey; Thomas, Beth (Transplant Infectious Disease, 2023)
Background Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication. The comparative prophylactic efficacy of antifungals in this patient population has not been reported, and an analysis is warranted. Methods This retrospective, matched cohort, single-center study, included AML, MDS, or HCT patients who began treatment or underwent transplant between January 1, 2015 and July 31, 2021. Isavuconazole patients were matched 1:2 with patients receiving posaconazole or voriconazole prophylaxis. Results A total of 126 patients were included, 42 received isavuconazole, 81 received posaconazole, and three received voriconazole. The majority of patients were male receiving secondary IFI prophylaxis while receiving steroids for treatment of GVHD. The incidence of possible, probable or proven IFI was 16.7% in the isavuconazole group compared to 10.7% in the posaconazole and voriconazole group (OR 1.28, 95% CI −0.9–1.4; p = .67). Hepatotoxicity occurred in 16 total patients, 14 receiving posaconazole and two receiving isavuconazole. Conclusion Patients who received isavuconazole prophylaxis during AML induction therapy or post-HCT experienced a similar incidence of breakthrough fungal infections compared to those who received posaconazole or voriconazole. These results suggest no difference in antifungal prophylactic efficacy; however larger prospective comparative studies are needed.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14045
Keywords: AML; acute myeloid leukemia; alloHSCT; fungal prophylaxis; isavuconazole; posaconazole; stem cell transplant; voriconazole

Donor call simulation: A novel medical education tool to evaluate trainees’ clinical decision‐making in transplant infectious disease - Sigler, Rachel; Wooten, Darcy; Kumar, Rebecca N.; Hand, Jonathan; Marschalk, Nicholas; Go, Roderick; Prakash, Katya; Stohs, Erica; Schaenman, Joanna; Law, Nancy (Transplant Infectious Disease, 2023)
Abstract Background Evaluating organ suitability for transplantation based on infection risk is a core competency in transplant infectious disease (TID). It is unclear if trainees have opportunities to practice during training. We created a simulation curriculum to develop and evaluate this skill among infectious disease (ID) trainees. Methods We created six simulation questions about organ suitability for transplant based on infection risk. During trainees’ TID rotations, faculty texted or paged the simulation cases posing as the transplant coordinator. Trainees had 15 min to ask questions before deciding the suitability of the organ and explained their clinical reasoning in a survey. Trainees completed a post‐simulation survey to evaluate its effectiveness. Results ID trainees, including residents and fellows on rotation, from seven centers participated. Eighty‐seven percent (13/15) of trainees felt the simulation was effective in teaching them this concept, and 80% (12/15) felt prepared for clinical practice. The proportion of correct responses was generally high among the six different cases (43%–100%); correct responses increased for some cases in the post‐activity survey. Of the 100 clinical reasoning decisions made during the activity, 19% were discordant, where the trainee correctly identified suitable organs for incorrect reasons. Conclusion Our simulation was effective in teaching when to accept or reject an organ for transplant and was a valuable educational tool. By evaluating clinical reasoning for decisions our simulation provides educators with nuanced insight and allows for targeted coaching. This study demonstrates a critical need for further educational tools in TID. image

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons - Singh, Nikhil; Thursky, Karin; Maron, Gabriela; Wolf, Joshua (Transplant Infectious Disease, 2023)
Background The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications. Discussion Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection-related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result. Conclusions The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk-benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14152
Keywords: antimicrobial stewardship; antimicrobials; bone marrow transplantation; febrile neutropenia; fluoroquinolone; hematology; levofloxacin; neutropenic fever; oncology; prophylaxis

SARS-CoV-2 Rebound With and Without Use of COVID-19 Oral Antivirals - Smith, Dallas J. (MMWR. Morbidity and Mortality Weekly Report, 2023)
CDC reviewed COVID-19 rebound studies among patients who

Short-course early outpatient remdesivir prevents severe disease due to COVID-19 in organ transplant recipients during the omicron BA.2 wave - Solera, Javier T.; Árbol, Berta G.; Bahinskaya, Ilona; Marks, Nikki; Humar, Atul; Kumar, Deepali (American Journal of Transplantation, 2023)
Solid organ transplant recipients (SOTr) remain at risk of severe COVID-19. Several previous early therapies are no longer effective against new circulating variants. We performed a prospective cohort study in outpatient adult SOTr during the omicron BA.2 wave (April–May 2022), to determine the effectiveness of 3 doses of remdesivir given within 7 days of symptoms onset. Patients were followed for at least 30 days. The primary outcome was hospitalization. Of 210 SOTr that had COVID-19, we included 192. The median age was 54.5 years and 61.5% were men. The most common transplants were kidney (41.7%), lung (19.3%), liver (18.8%), and heart (6.3%). Most patients (90.1%) had previously received !3 COVID-19 vaccine doses. Fifteen (7.8%) were hospitalized, 5(2.6%) required supplemental oxygen, 3(1.6%) ICU admission, and 2(1%) mechanical ventilation with 2(1%) deaths. Age, the number of comorbidities, prednisone chronic treatment, and lung transplant were risk factors for hospitalization. Early remdesivir signiﬁcantly decreased the hospitalization rate: adjusted hazard ratio 0.12 (95% CI: 0.03–0.57). The adjusted number needed to treat to prevent one hospitalization was 15.2 (95% CI: 13.6–31.4). No patient that received early remdesivir needed ICU admission or died. In a cohort of SOTr with COVID-19 infection, administration of 3-dose early remdesivir independently reduced the disease severity.

Opportunities for Antimicrobial Stewardship Interventions Among Solid Organ Transplant Recipients - Stohs, Erica J.; Gorsline, Chelsea A. (Infectious Disease Clinics of North America, 2023)

The association of donor hepatitis C virus infection with 3-year kidney transplant outcomes in the era of direct-acting antiviral medications - Sutcliffe, Siobhan; Ji, Mengmeng; Chang, Su-Hsin; Stewart, Darren; Axelrod, David A.; Lentine, Krista L.; Wellen, Jason; Alrata, Louai; Gupta, Gaurav; Alhamad, Tarek (American Journal of Transplantation, 2023)
To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid ampliﬁcation test positive [NATþ, n ¼ 2331] or antibody positive (Abþ)/NATÀ [n ¼ 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Abþ/NATÀ (aHR ¼ 0.91; 95% conﬁdence interval [CI], 0.75-1.10) and HCV NATþ (aHR ¼ 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NATþ kidneys were associated with a higher 1-year estimated glomerular ﬁltration (63.0 vs 61.0 mL/min/1.73 m2, P ¼ .007) and lower risk of delayed graft function (aOR ¼ 0.76; 95% CI, 0.680.84) compared with HCV-negative kidneys. Our ﬁndings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.

High-titer post-vaccine COVID-19 convalescent plasma for immunocompromised patients during the first omicron surge - Tayyar, Ralph; Wong, Lisa Kanata; Dahlen, Alex; Shu, Elaine; Pandey, Suchitra; Liu, Anne Y. (Transplant Infectious Disease, 2023)
Background Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID-19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID-19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer in convalescent donors. Methods We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID-19 who received high-titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre-omicron COVID-19. Data on safety and outcomes were extracted. Results A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS-CoV-2 antibody results 8- to 37-fold higher than the Food and Drug Administration's cutoff for high-titer CCP. There were two mild transfusion reactions. A total of 30-day mortality was 4.5%. There were no differences in 100-day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30-day post-CCP compared to those with lower immunosuppression. Conclusions CCP is a safe, globally available treatment for immunocompromised patients with COVID-19. Mortality was lower in our cohort than that of COVID-19 patients with similar immunocompromising conditions. Post-vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post-vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.14055
Keywords: COVID-19 convalescent plasma; SARS-CoV-2; hematopoietic cell transplant; immunocompromised patients; solid organ transplant

Legionnaires’ Disease in Solid Organ Transplant Recipients - Thizy, Guillaume; Flahault, Adrien; Scemla, Anne; Roux, Olivier; Jarraud, Sophie; Lebeaux, David; Pouchot, Jacques; Gautier-Vargas, Gabriela; Malvezzi, Paolo; Murris, Marlene; Vuotto, Fanny; Girerd, Sophie; et al. (CHEST, 2023)

Impact of Culture-Positive Preservation Fluid on Early Morbidity and Mortality After Lung Transplantation - Tran-Dinh, Alexy; Tir, Imane; Tanaka, Sébastien; Atchade, Enora; Lortat-Jacob, Brice; Jean-Baptiste, Sylvain; Zappella, Nathalie; Boudinet, Sandrine; Castier, Yves; Mal, Hervé; Mordant, Pierre; Ben Abdallah, Iannis; et al. (Transplant International, 2023)
Background: The prevalence, risk factors and outcomes associated with culture-positive preservation fluid (PF) after lung transplantation (LT) are unknown. Methods: From January 2015 to December 2020, the microbiologic analyses of PF used to store the cold ischaemia-placed lung graft(s) of 271 lung transplant patients were retrospectively studied. Culture-positive PF was defined as the growth of any microorganism. Results: Eighty-three (30.6%) patients were transplanted with lung grafts stored in a culture-positive PF. One-third of culture-positive PF were polymicrobial. Staphylococcus aureus and Escherichia coli were the most frequently isolated microorganisms. No risk factors for culture-positive PF based on donor characteristics were identified. Forty (40/83; 48.2%) patients with had postoperative pneumonia on Day 0 and 2 (2/83; 2.4%) patients had pleural empyema with at least one identical bacteria isolated in culture-positive PF. The 30-day survival rate was lower for patients with culture-positive PF compared with patients with culture-negative PF (85.5% vs. 94.7%, p = 0.01). Conclusion: Culture-positive PF has a high prevalence and may decrease lung transplant recipient survival. Further studies are required to confirm these results and improve understanding of the pathogenesis of culture-positive PF and their management.
Publisher: Frontiers

Current Concepts in the Diagnosis and Management of Pneumocystis Pneumonia in Solid Organ Transplantation - Trubin, Paul A.; Azar, Marwan M. (Infectious Disease Clinics of North America, 2023)

Fatal HSV-2 primary infection most likely acquired by kidney transplantation: a case report - Truffot, Aurélie; Noble, Johan; Dartevel, Anaïs; Chevalier, Eloi; Dard, Celine; Giovannini, Diane; Andreani, Julien; Burrel, Sonia; Boutolleau, David; Epaulard, Olivier; Pavese, Patricia; Morand, Patrice; et al. (International Journal of Antimicrobial Agents, 2023)

COVID-19 Prevention in Solid Organ Transplant Recipients: Current State of the Evidence - Vafea, Maria Tsikala; Haidar, Ghady (Infectious Disease Clinics of North America, 2023)

Conversion to mTOR Inhibitor to Reduce the Incidence of Cytomegalovirus Recurrence in Kidney Transplant Recipients Receiving Preemptive Treatment: A Prospective, Randomized Trial - Viana, Laila Almeida; Cristelli, Marina Pontello; Basso, Geovana; Santos, Daniel Wagner; Dantas, Marcus Taver Costa; Dreige, Yasmim Cardoso; Requião Moura, Lucio R.; Nakamura, Monica Rika; Medina-Pestana, Jose; Tedesco-Silva, Helio (Transplantation, 2023)
Background. Although mammalian target of rapamycin inhibitors (mTORi) are associated with a lower incidence of the first episode of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving calcineurin inhibitors (CNIs), the efficacy and safety of the conversion from the antimetabolite to an mTORi for the prevention of CMV recurrence are unknown. Methods. In this single-center prospective randomized trial, low-immunological-risk, CMV-positive kidney transplant recipients receiving preemptive therapy were randomized to be converted (sirolimus [SRL]) or not (control [CTR]) immediately after the treatment of the first episode of CMV infection/disease and were followed for 12 mo. A sample size of 72 patients was calculated to demonstrate a 75% reduction in the incidence of CMV recurrence (80% power, 95% confidence level). Results. Of 3247 adult kidney transplants performed between September 13, 2015, and May 7, 2019, 1309 (40%) were treated for the first CMV infection/disease, and 72 were randomized (35 SRL and 37 CTR). In the SRL group, there were no episodes of CMV recurrence, compared with 16 patients in the CTR group (0% versus 43%; P < 0.0001). Four patients had a second and 1 a third recurrent CMV event. Three of them were converted to SRL and did not develop any further CMV events. There were no differences in the incidence of acute rejection, drug discontinuation, kidney function, and patient and graft survival at 12 mo. Conclusions. These data suggest that, in CMV-positive kidney transplant recipients, the conversion from an antiproliferative drug to SRL after the first CMV episode is an effective and safe strategy for recurrent episodes.

Cell-free next-generation sequencing impacts diagnosis and antimicrobial therapy in immunocompromised hosts: A retrospective study - Vissichelli, Nicole C.; Morales, Megan K.; Kolipakkam, Bharadhwaj; Bryson, Alexandra; Sabo, Roy T.; Toor, Amir A. (Transplant Infectious Disease, 2023)
Background Cell-free next-generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non-invasive nature make it a promising supplement to standard of care. Methods This retrospective, observational single-center study at a tertiary care medical center in Virginia investigated the use of cfNGS in clinical practice. Patients over age 18 years with cfNGS performed for any indication were included. The primary outcome was detection of bacteria and/or fungi on cfNGS. The secondary outcomes were concordance, and abundance of fungal and bacterial organism concentration detected over time from symptom onset, and clinical impact. Results Thirty-six patients (92% immunosuppressed) were identified and included. Twenty-one (58%) tests detected one to five organisms (14/21 bacteria, 8/21 fungi, and 6/21 viruses). The clinical impact of cfNGS was positive in 52.8% of cases, negative in 2.8%, and negligible in 44.4%. Positive tests prompted therapy changes in 12 of 21 patients; six of 20 bacteria and seven of eight fungi identified were considered clinically pathogenic. Three bacteria identifications and six fungi identifications prompted targeted treatment. When fungal species were not identified by cNFGS, antifungal de-escalation occurred in seven patients. Conclusion cfNGS assisted in critical management changes, including initiation of treatment for identified organisms and antimicrobial de-escalation. Its non-invasive nature and rapid turnaround time make this an important adjunct to standard of care testing that may assist in providing earlier, targeted therapy, especially when opportunistic pathogens remain high on the differential diagnosis.
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/tid.13954
Keywords: Karius; cell-free DNA; immunocompromised; next-generation sequencing