Mucormycosis - Kontoyiannis, Dimitrios P.; Walsh, Thomas J. (New England Journal of Medicine, 2026)

American Society for Transplantation and Cellular Therapy Series #11: Updated Cytomegalovirus Guidelines in Hematopoietic Cell Transplant and Cellular Therapy Recipients - Khawaja, Fareed; Zamora, Danniel; Yong, Michelle K.; Hakki, Morgan; Goscicki, Breana K.; Danziger-Isakov, Lara; Lin, Andrew; Carpenter, Paul A.; Boeckh, Michael; Papanicolaou, Genovefa A.; Dadwal, Sanjeet S.; Chemaly, Roy F. (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2025)
Keywords: Cellular therapy; Chimeric antigen receptor therapy; Cytomegalovirus; Hematopoietic cell transplant

Complicated Urinary Tract Infections (cUTI): Clinical Guidelines for Treatment and Management - Trauter, Barbara W.; Cortes-Penfield, Nicolas W.; Gupta, Kalpana; Hirsch, Elizabeth B.; Horstman, Molly; Moran, Gregory J.; Colgan, Richard; O'Horo, John C.; Ashraf, Muhammed S.; Connolly, Shannon; Drekonja, Dimitri M.; Grigoryan, Larissa; et al. (2025)

2025 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Histoplasmosis: Treatment of Asymptomatic Histoplasma Pulmonary Nodules (Histoplasmomas) and Mild or Moderate Acute Pulmonary Histoplasmosis in Adults, Children, and Pregnant People - Arnold, Sandra R; Spec, Andrej; Baddley, John W; Pappas, Peter; Lentz, Robert J; Wolf, Joshua; Kauffman, Carol A; Ardura, Monica I; Badreldin, Nevert; Bahr, Nathan C; Bloch, Karen; Miller, Rachel A; et al. (Clinical Infectious Diseases, 2025)
As the first part of an update to the clinical practice guideline on the management of histoplasmosis in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, we present 4 updated recommendations. These recommendations span treatment of asymptomatic Histoplasma pulmonary nodules (histoplasmomas), mild acute pulmonary histoplasmosis, and moderate acute pulmonary histoplasmosis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Cannabis Use and Transplant Recipients - Power2Save (American Society of Transplantation, 2025)
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Drinking Water Safety After Transplant - Power2Save (American Society of Transplantation, 2025)
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Food Safety After Transplant - Power2Save (American Society of Transplantation, 2025)
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Insect and Tick Bite Guide for Recipients - Power2Save (American Society of Transplantation, 2025)
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Interacting with Animals After your Transplant - Power2Save (American Society of Transplantation, 2025)
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Minimizing Workplace Risk After Transplant For Healthcare and… - Power2Save (American Society of Transplantation, 2025)
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Outdoor Activity Guide for Transplant Recipients - Power2Save (American Society of Transplantation, 2025)
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Safe Living after Transplant: Sexual Activity - Power2Save (American Society of Transplantation, 2025)
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Staying Safe After Transplant: Handwashing - Power2Save (American Society of Transplantation, 2025)
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Staying Safe After Transplant: Masking - Power2Save (American Society of Transplantation, 2025)
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Staying Safe After Transplant: Religious Pilgrimage - Power2Save (American Society of Transplantation, 2025)
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Staying Safe After Transplant: Vaccines for Adults - Power2Save (American Society of Transplantation, 2025)
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Staying Safe After Transplant When Traveling Outside of the US and… - Power2Save (American Society of Transplantation, 2025)
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Water Recreation Safety After Transplant - Power2Save (American Society of Transplantation, 2025)
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Working With The Public - A Recipient Guide - Power2Save (American Society of Transplantation, 2025)
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Workplace Risk After Transplant - Power2Save (American Society of Transplantation, 2025)
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Educational Resources: Food - Power2Save (American Society of Transplantation, 2025)
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American Society for Transplantation and Cellular Therapy Series #10: Management of Parainfluenza and Human Metapneumovirus Infections in Hematopoietic Cell Transplantation and Cellular Therapy Recipients - Batista, Marjorie Vieira; Chaer, Firas El; Englund, Janet A.; Boeckh, Michael; Carpenter, Paul A.; Dadwal, Sanjeet S.; Waghmare, Alpana; Navarro, David; Hirsch, Hans H.; Piñana, Jose Luis; Papanicolaou, Genovefa A.; Chemaly, Roy F. (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2025)
Keywords: Cellular therapy; Guidelines; Hematopoietic cell transplantation; Human metapneumovirus; Parainfluenza virus; Paramyxovirus

Measles Guidance Document for the Transplant Community - AST, Infectious Diseases Community of (American Society of Transplantation, 2025)
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IDSA COVID-19 Guideline, Part 1: Treatment and Management - Adarsh Bhimraj*, Rebecca L. Morgan**, Amy Hirsch Shumaker, Valery Lavergne**, Lindsey Baden, Vincent Chi-Chung Cheng, Kathryn M. Edwards, Rajesh Gandhi, Jason Gallagher, William J. Muller, John C. O’Horo, Shmuel Shoham, M. Hassan Murad**, Reem A. Mustafa* (2025)
COVID-19 is a pandemic with a rapidly increasing incidence of infections and deaths. Many pharmacologic therapies are being used or considered for treatment. Given the rapidity of emerging literature, IDSA felt the need to develop living, frequently updated evidence-based guidelines to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19 infection. Summarized here are the recommendations with comments related to the clinical practice guideline for the treatment and management of COVID-19.

American Society for Transplantation and Cellular Therapy Series #9: Management of Human Herpesvirus 6B After Hematopoietic Cell Transplantation and Chimeric Antigen Receptor-T-Cell Therapy - Kampouri, Eleftheria; Handley, Guy; Phan, Tuan L.; Lee, Yeon Joo; Shaw, Ryan; Carpenter, Paul A.; Dadwal, Sanjeet S.; Chemaly, Roy F.; Papanicolaou, Genovefa A.; Ogata, Masao; Boeckh, Michael; Zerr, Danielle M.; et al. (Transplantation and Cellular Therapy, 2025)
The Practice Guidelines Committee and the Transplant Infectious Disease Special Interest Group of the American Society for Transplantation and Cellular Therapy developed guidelines focusing on human herpesvirus 6B (HHV-6B). A compendium-style approach was used to address a series of standalone frequently asked questions (FAQs), supported by tables and figures to spotlight key concepts. Adult and pediatric infectious disease and hematopoietic cell transplantation (HCT) content experts developed these FAQs and finalized recommendations after consensus was reached. This ninth topic in the series focuses on the relevant risk factors, diagnostic considerations, prophylaxis, and treatment approaches relevant to HHV-6B infections after HCT and chimeric antigen receptor-T-cell therapy.
Keywords: Allogeneic hematopoietic cell transplant; CAR-T-cell therapy; Encephalitis; HHV-6; Inherited chromosomally integrated HHV-6

Virus-Specific T-Cell Therapy for Prophylaxis and Treatment of Cytomegalovirus Infections After Transplantation: a Scoping Review - Fung, Jollee S T; Wright, Robert C; Bharaj, Dilpreet K; Alghamdi, Amenah; Hesson, Donna; Delisle, Jean-Sébastien; Schweitzer, Lorne; Avery, Robin K; Belga, Sara (Clinical Infectious Diseases, 2025)
Cytomegalovirus (CMV) infection is a leading complication following hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT). Virus-specific T cells (VSTs) have been used for the prophylaxis and treatment of CMV infections. We conducted a scoping review to catalogue and characterize the existing literature.Systematic searches were performed in collaboration with an expert librarian. Inclusion criterion was the use of CMV-VST for prophylaxis or treatment in HSCT and SOT patients. Major exclusion criteria were case reports and series with <5 cases. Databases were queried from inception to 31 May 2024. Of the 2587 identified abstracts, full text review was performed on 92 articles, and 67 studies underwent final data extraction.Most studies were in the HSCT population. The CMV infection rate was 28% (interquartile range [IQR], 14%–44%) when CMV-VSTs were used as prophylaxis. Response rates for non–refractory and/or resistant (R/R) infections and R/R infections in HSCT patients were 98% (IQR, 70%–100%) and 70% (IQR, 56%–88%), respectively. Four studies included SOT patients with R/R infections, demonstrating a response rate of 15%–64%. Variables including donor/recipient serostatus and antiviral use were heterogeneously reported, and various definitions of CMV infection and response were used. CMV-VSTs were well-tolerated with minimal adverse events reported.CMV-VSTs are more commonly used in HSCT patients with limited data in SOT patients, and differential reporting of key variables precludes extrapolation. A standardized registry should be considered for future studies with additional focus on the optimal dosing, timing, and interaction with concurrent antivirals.

The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation - Kotton, Camille N.; Kumar, Deepali; Manuel, Oriol; Chou, Sunwen; Hayden, Randall T.; Danziger-Isakov, Lara; Asberg, Anders; Tedesco-Silva, Helio; Humar, Atul; Group*, on behalf of The Transplantation Society International CMV Consensus (Transplantation, 2025)
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American Society of Transplantation and Cellular Therapy Series: #8-Management and Prevention of Non-Aspergillus Molds in Hematopoietic Cell Transplantation Recipients - Douglas, Abby P.; Lamoth, Frederic; John, Teny M.; Groll, Andreas H.; Shigle, Terri Lynn; Papanicolaou, Genovefa A.; Chemaly, Roy F.; Carpenter, Paul A.; Dadwal, Sanjeet S.; Walsh, Thomas J.; Kontoyiannis, Dimitrios P. (Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, 2025)
Keywords: Guideline; Hematopoietic cell transplant; Invasive fungal infection; Mold

Incidence of Breakthrough Fungal Infections in Patients with Isavuconazole Prophylaxis: A Systematic Review and Meta-Analysis - Ishida, Keiko; Haraguchi, Mizuki; Kimura, Muneyoshi; Araoka, Hideki; Natori, Akina; Reynolds, John; Raja, Mohammed; Natori, Yoichiro (Open Forum Infectious Diseases, 2025)
Abstract Background Isavuconazole (ISA) is a newer triazole which has activity against most mold species and has been utilized for prophylaxis as well as treatment in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HSCT). However, several studies have documented breakthrough invasive fungal infections (bIFIs). Thus, we conducted a systematic review and meta-analysis to investigate the incidence of bIFIs among patients receiving ISA prophylaxis. Methods We conducted a systematic review and meta-analysis of the published literature using the concept of ISA, HSCT and HM from 5 search engines. Pooled incidence of bIFI while on ISA prophylaxis in patients with HSCT and HM, was calculated using DerSimonian-Laird random effect model. Results Thirty-five and 19 studies were included in the systematic review, and the meta-analysis, respectively. Total of 991 patients were identified as using ISA prophylaxis, and the majority had either acute myeloid leukemia or myelodysplastic syndrome (69.9%). The pooled incidence of proven/probable bIFIs was 7% (95% CI 4-12%, I2: 55%). The most common pathogen was Aspergillus species (43.1%), followed by Candida (22.4%), and Mucorales (12.1%). In 19 studies, mortality was documented and ranged between 0-100%, majority of which were more than 50%. Conclusions We found high incidence of bIFIs while on ISA prophylaxis in HM/HSCT recipients, with high mortality. Given the lack of randomized clinical trials evaluating ISA in this indication, it’s role in prophylaxis remains unclear.

Levofloxacin to prevent bacterial infection in patients with acute myeloid leukemia treated by venetoclax and azacitidine: a Toulouse-Bordeaux DATAML registry study - Brousse, Xavier; Rasandisona, Nicolas; Bérard, Emilie; Leroy, Harmony; Delavigne, Karen; Mottal, Nathan; Tavitian, Suzanne; Leguay, Thibaut; Lapierre, Léopoldine; Delabesse, Eric; Bidet, Audrey; Gauthier, Martin; et al. (Open Forum Infectious Diseases, 2025)
Abstract Objectives Antibiotic prophylaxis for patients with cancer remains a controversial issue and is not broadly recommended for hematological malignancies. The venetoclax (VEN) and azacitidine (AZA) combination allows for high rates of complete remission in acute myeloid leukemia (AML) but enhances the incidence of febrile neutropenia (FN) compared to AZA alone, making primary antibiotic prophylaxis a relevant question. Patients and Methods Patients with AML who received VEN-AZA were selected from the DATAML registry to investigate the use of levofloxacin (LEVO) prophylaxis, administered at 500 mg/day from day 10 following the first course of VEN-AZA, until neutrophil recovery (>0.5x109/L). Results A cohort of 258 patients was identified (median age 69.8 years, IQR 20.4-87.4), 72 of them having received LEVO and 186 treated with standard of care (SOC). VEN-AZA was used for newly diagnosed AML in 52.7% of cases. FN occurred in 33.3% of LEVO patients vs. 37.1% of SOC patients (p=0.572). Time from day 10 VEN-AZA to FN was significantly delayed in LEVO patients (12.5 days vs 8 in SOC; p=0.037). Pulmonary infections were considerably reduced by LEVO (10.2% vs 1.4%, p=0.018) as well as those involving enterobacterales (9.1% vs 1.4%; p=0.029). No early increase in fluoroquinolone resistance was detected (p=0.142). Conclusion Levofloxacin as primary prophylaxis in patients with AML treated with VEN-AZA seems to decrease the rate of documented infections even if the incidence of FN was not significantly decreased. This prophylaxis shaped a different clinical and microbiological landscape without significant increase of antibiotic resistance.

CDC: Clinical Overview of Measles - CDC (Measles (Rubeola), 2025)
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Impact of Attaining an Aggressive Pharmacokinetic-Pharmacodynamic Target on the Clinical Efficacy of Continuous Infusion β-Lactam Therapy for Early Posttransplant Gram-Negative Infections in Critically Ill Orthotopic Liver Transplant Recipients: An Interim Analysis of a 3-Year Prospective, Observational Study - Gatti, Milo; Rinaldi, Matteo; Laici, Cristiana; Bonazzetti, Cecilia; Vizioli, Luca; Ambretti, Simone; Morelli, Maria Cristina; Siniscalchi, Antonio; Giannella, Maddalena; Viale, Pierluigi; Pea, Federico (The Journal of Infectious Diseases, 2025)
Abstract Background To assess the impact of attaining aggressive β-lactam (BL) pharmacokinetic-pharmacodynamic (PK/PD) targets on clinical efficacy in critically ill orthotopic liver transplant (OLT) recipients with documented early gram-negative infections. Methods The study prospectively enrolled OLT recipients admitted to the posttransplant intensive care unit between June 2021 and May 2024; they had documented gram-negative infections treated with targeted therapy continuous infusion (CI) BLs and underwent therapeutic drug monitoring (TDM)-guided BL dosing adjustment within the first 72 hours. Aggressive PK/PD target attainment was measured. Multivariate logistic regression analyses were performed to test independent variables associated with 30-day resistance occurrence. Results Fifty critically ill OLT recipients were treated with CI BL in monotherapy (n = 34) or combination (n = 16) therapy for documented gram-negative infections No significant difference in clinical/microbiological outcome emerged between monotherapy and combination therapy. In 4 patients (8.0%), resistance developed within 30 days. At multivariate analysis, failure in attaining an aggressive BL PK/PD target emerged as the only independent predictor of 30-day resistance development (odds ratio, 14.33 [95% confidence interval, 1.46–140.53]; P = .02). Conclusions Attaining an aggressive PK/PD target with CI BLs in critically ill OLT recipients with documented gram-negative infections could represent an effective strategy for minimizing resistance occurrence to the selected BL.

Performance of mp-tNGS in Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis in Nonneutropenic Patients - Wang, Hansheng; Chen, Xiao; You, Hui; Wang, Yunyun; Xia, Xianru; Tang, Yijun; Ren, Tao; Wang, Meifang (The Journal of Infectious Diseases, 2025)
Abstract Background Multiplex polymerase chain reaction (PCR)-based targeted next-generation sequencing (tNGS) is a promising tool for distinguishing lower respiratory tract infections in clinical practice, and its detectable pathogen spectrum can cover more than 95% of clinical cases, but there is limited information on systematic evaluation of the clinical use of multiplex PCR-based tNGS (mp-tNGS) in invasive pulmonary aspergillosis (IPA) cases. We aim to assess mp-tNGS in bronchoalveolar lavage fluid (BALF) for Aspergillus detection in patients with suspected IPA to provide a reliable basis for initiating antifungal therapy without microbiological or histopathological evidence. Methods We prospectively enrolled a cohort of consecutive patients with suspected IPA; all had undergone serum/BALF galactomannan antigen (GM), BALF mp-tNGS, and traditional tests (direct smear and culture of respiratory specimens). EORTC/MSG and FUDICU criteria or clinical compound diagnosis were used for IPA diagnosis. Results Thirty-two patients were diagnosed with IPA and 42 with non-IPA. Compared with the final diagnosis, the sensitivity of BALF mp-tNGS was 87.5%, while the sensitivities of traditional tests, serum GM, and BALF GM assay were 43.8%, 21.9%, and 62.5%, respectively. The specificity of BALF mp-tNGS was 90.5%, which was similar to traditional tests. The average turnaround time for Aspergillus detection by BALF mp-tNGS was 22.10 hours (SD 2.49 hours), which was significantly faster than traditional tests. Conclusions BALF mp-tNGS showed good performance in identification of Aspergillus in nonneutropenic IPA patients. Importantly, positive mp-tNGS in BALF can provide a basis for early antifungal therapy before microbiological evidence is available.

Influenza Vaccination Strategies in Patients with Hematologic Cancer - Hall, Victoria G.; Smibert, Olivia C.; Sullivan, Sheena G.; Lim, Chhay; Barr, Ian G.; Peck, Heidi; Fuge-Larsen, Paula; Demajo, Jessica; Klimevski, Emily; Tennakoon, Surekha; Saunders, Natalie R.; Joyce, Trish; et al. (New England Journal of Medicine, 2025)

Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline - Saukkonen, Jussi J.; Duarte, Raquel; Munsiff, Sonal S.; Winston, Carla A.; Mammen, Manoj J.; Abubakar, Ibrahim; Acuña-Villaorduña, Carlos; Barry, Pennan M.; Bastos, Mayara L.; Carr, Wendy; Chami, Hassan; Chen, Lisa L.; et al. (American Journal of Respiratory and Critical Care Medicine, 2025)
Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals.
Keywords: adults; children; drug-resistant; drug-susceptible; tuberculosis

Prevention of Infections Among Pediatric Solid Organ Transplant Recipients With Asplenia or Hyposplenism - Espinoza-Candelaria, Gabriela J.; Yildirim, Inci; Yamada, Masaki; Minniear, Timothy D.; L'Huillier, Arnaud G.; Dulek, Daniel E.; Danziger-Isakov, Lara; Ardura, Monica I.; Michaels, Marian G. (Pediatric Transplantation, 2025)
Pediatric solid organ transplant (SOT) recipients with splenic dysfunction are at increased risk for infections, and tailored guidance on the management of asplenia/hyposplenism among SOT recipients is often lacking. The purpose of this article is to provide practice recommendations via a frequently asked questions (FAQs) format that focuses on three main domains: the identification of asplenia/hyposplenism among SOT recipients/candidates, prophylactic strategies for mitigating the risk of invasive disease associated with splenic dysfunction in the context of transplantation, and the provision of appropriate patient counseling on the risks associated with asplenia/hyposplenism. Answers to the FAQs are based on international expert opinion informed by practices for managing splenic dysfunction and associated data in other populations with asplenia. Gaps in the existing literature and relevant research aims are emphasized.
Keywords: asplenia; prevention; prophylaxis; splenectomy; vaccines

Detection of viral RNA and DNA and immune response following administration of live attenuated measles and varicella vaccines in children with chronic liver disease - Kemme, Sarah; Canniff, Jennifer D.; Garth, Krystle M.; Li, Shaobing; Mysore, Krupa; Weinberg, Adriana; Feldman, Amy G. (American Journal of Transplantation, 2025)

Research Advice for Early Career Transplant Infectious Disease Clinicians - Kumar, Rebecca N.; Scolarici, Michael J.; Gorsline, Chelsea; Danziger-Isakov, Lara; Baddley, John; Harris, Courtney E. (Transplant Infectious Disease, 2025)
As part of an ongoing series of social media discussions, the Transplant Infectious Diseases Early Career Network hosted an open forum for the transplant infectious disease community to discuss the development of research careers for junior faculty. Topics discussed included opportunities for research, identifying potential research questions, institutional support, grant funding, common barriers to research, and trainee involvement. The forum highlighted symbiotic relationships between junior faculty and trainees. The insights from the forum provide a valuable resource for early-career transplant infectious diseases (TID) researchers.
Keywords: collaborations; early career; funding; institutional support; research

Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation - Pittet, Laure F.; Gualtieri, Renato; Verolet, Charlotte M.; L’Huillier, Arnaud G.; Wildhaber, Barbara E.; McLin, Valérie A.; Posfay-Barbe, Klara M. (American Journal of Transplantation, 2025)

Invasive Candidiasis in Pediatric Hematologic Malignancy: Increased Risk of Dissemination With Candida tropicalis - Said, Amira M.; Afridi, Faraz; Redell, Michele S.; Vrana, Chelsea; O’Farrell, Candelaria; Scheurer, Michael E.; Dailey Garnes, Natalie J.; Gramatges, Maria Monica; Dutta, Ankhi (Pediatric Infectious Disease Journal, 2025)
Background: Candida species are the most common cause of invasive fungal disease, and children with hematologic malignancy are at increased risk. Non- albicans Candida (NAC) now account for more than half of all invasive candidiasis (IC) and carry a worse prognosis. We aimed to compare the epidemiology, risk factors, organ dissemination, biomarkers and outcomes in IC based on the species implicated and evaluate trends in antifungal resistance over time. Methods: Patients 0–18 years of age with hematologic malignancy and IC at 2 centers were included. Fifty-three patients from 2011 to 2022 were identified. Information related to demographics, host and risk factors, Candida species and antifungal susceptibilities, treatment and outcomes was collected via retrospective chart review. Data were analyzed at the species level. Results: The incidence rate of IC was 29 per 1000 patients with leukemia and lymphoma. The median time to infection from diagnosis of malignancy was 38 days. Candida tropicalis (n = 17; 30%) was the most identified species followed by Candida albicans (n = 14; 25%). Patients with C. tropicalis infection were more likely to have dissemination to the eyes ( P = 0.035), spleen ( P = 0.001) and skin ( P = 0.003) than patients with C. albicans or other NAC. Of the 34 patients who underwent dilated retinal examination, 24% (n = 8) had evidence of intraocular candidiasis. Seven of the 8 patients with intraocular disease had prolonged candidemia (3 or more days; P = 0.003). The 12-week crude mortality rate was 16.9%. Conclusions: NAC, specifically C. tropicalis , accounted for most of the IC in children with hematological malignancies. Screening for intraocular candidiasis continues to play an important role in patients with IC, and future studies are needed to determine if screening can be limited to patients with select risk factors.

Extracorporeal Membrane Oxygenation in Adults - Vyas, Ankit; Patel, Viral; Wang, Cecily F. (StatPearls, 2025)
Extracorporeal membrane oxygenation (ECMO) is a life support modality for adults and children with life-threatening cardiac and pulmonary failure that is refractory to conventional therapy or unresponsive to cardiopulmonary resuscitation (CPR). The ECMO circuit consists of a pump and an oxygenator that temporarily replace cardiac and pulmonary function, allowing time for organ recovery. According to the Extracorporeal Life Support Organization (ELSO), ECMO was used in 151,683 patients through 2020, including 45,205 neonates, 30,743 children, and 75,735 adults. In 1990, ECMO was available in 83 centers; by 2020, the number of ECMO centers had grown to 492. As of July 2024, more than 185,000 cumulative ECMO runs have been reported across over 1200 centers worldwide, reflecting the rapid global expansion of this therapy.[ECLS International Summary of Statistics] Venovenous (VV) ECMO provides respiratory support, whereas venoarterial (VA) ECMO supports both cardiac and respiratory function. ECMO is a supportive therapy rather than a disease-modifying intervention. In 1944, Kolff and Berk demonstrated blood oxygenation using cellophane chambers in an artificial kidney. In 1953, Gibbon applied artificial oxygenation and perfusion during the first successful open-heart operation. Early oxygenators included film and bubble designs, both associated with intravascular hemolysis, systemic inflammation, platelet destruction, and embolization. In 1956, Clowes and Basler developed the first prototype membrane oxygenator suitable for cardiopulmonary bypass (CPB). Rashkind used a bubble oxygenator in 1965 to treat neonatal respiratory failure. In 1969, Dorson et al reported the use of a membrane oxygenator in infant CPB. Baffes et al described ECMO use during infant cardiac surgery in 1970. In 1972, Hill et al reported the first use of ECMO for adult respiratory failure, and Bartlett et al achieved the first successful neonatal ECMO case in 1975 for severe respiratory distress. From the 1980s to the early 2000s, ECMO circuits typically used either silicone membrane or polypropylene hollow fiber oxygenators. These oxygenators were prone to plasma leakage, prompting the development of polymethylpentene oxygenators. The newer generation polymethylpentene models are more durable, provide improved gas exchange, and result in less blood trauma. A recent single-center pilot study comparing 4 polymethylpentene oxygenators found low oxygenator failure rates, but notable differences in resistance and post-oxygenator PaO2, emphasizing the need to tailor device choice to patient-specific requirements during long ECMO runs. Kolobow and colleagues analyzed ECMO outcomes in a National Institutes of Health trial conducted in 1981. That same year, Gattinoni et al demonstrated successful ECMO use in a large population of patients with acute respiratory distress syndrome (ARDS). By 1987, Gattinoni's group reported approximately 50% survival. In 1994, a randomized controlled trial by Morris et al did not show improved outcomes with low-flow VV ECMO versus conventional ventilation in ARDS. Survival in the control group was 42%, compared to 33% in the ECMO group. Interest in ECMO resurged after publication of the CESAR trial in 2009, which randomized 180 patients across 68 centers. CESAR demonstrated significantly improved outcomes—including reduced mortality and disability—among patients with severe respiratory failure treated with ECMO versus conventional management. ECMO use expanded dramatically during the COVID-19 pandemic. Large-scale ELSO registry analyses have confirmed hospital survival rates of 48% to 60% in patients with severe viral ARDS when ECMO is initiated at experienced centers.

Chimeric Antigen Receptor T-Cell Therapy - Zhang, Chen; Durer, Seren; Thandra, Krishna C.; Kasi, Anup (StatPearls, 2025)
Chimeric antigen receptors (CARs) are recombinant receptors for antigens that redirect the specificity and function of T lymphocytes or other immune cells in a single molecule. The concept of using CARs in cancer immunotherapy is that CARs, which are programmed to target tumor-associated antigens, can be replicated rapidly and homogeneously. Direct infusion of these armed tumor-targeting T-cells bypass the barriers and kinetics of active immunization. Unlike general passive immunization using a direct antibody, CAR-modified T-cells with supraphysiologic activities work as an active medication, interacting with tumor-associated antigens, which results in both immediate and long-term effects of anti-neoplasm.

Prevalence of Trypanosoma cruzi Infection in Solid Organ Transplant Recipients: A Neglected Disease in America - Contreras, German A; Golovko, George (Open Forum Infectious Diseases, 2024)
This study investigates the prevalence of Trypanosoma cruzi infection among solid organ transplant recipients in the United States from 2019 to 2023 before transplantation. Utilizing data from a large multicenter network, we identified a rising seroprevalence of 4.8% from 1523 solid organ transplant recipients at the time of the evaluation for transplantation, particularly among lung and heart transplant recipients. The findings highlight the need for improved screening protocols to address this neglected tropical disease in transplant populations.

Efficacy of Letermovir for Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant - Muhsen, Ibrahim N.; Shaver, Kristen E.; Wang, Tao; Wu, Mengfen; Lulla, Premal; Ramos, Carlos A.; Kamble, Rammurti T.; Heslop, Helen E.; Carrum, George; Hill, LaQuisa C. (Transplantation and Cellular Therapy, 2024)
In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy or CMV disease) within 100 days post-transplant. Secondary outcomes included the cumulative incidence of acute GvHD (grade ≥ 2), the cumulative incidence of extensive chronic GvHD, and overall survival. A total of 84 alemtuzumab TCD URD allo-HSCT recipients were included in the analysis, 30 of whom received letermovir (letermovir group) and 54 who did not receive letermovir (control group). The median age was 59 years (range: 26-75 years) and 55.5 years (range: 20-73 years) in the letermovir and control group, respectively. Most recipients (66.7%) in both groups received unrelated matched allografts, and myeloid neoplasms were the most common indication for allo-HSCT. A significantly lower cumulative incidence of significant CMV infection within 100 days was seen in the letermovir group compared to the control group (10.0% [95% CI: 2.5-23.9%] versus 55.6% [95% CI: 41.2-67.8%], P < .0001). There was no statistically significant difference in the incidence of acute GvHD (grade ≥ 2) or overall survival between the 2 groups. However, lower rates of extensive chronic GvHD were noted in the letermovir group (10.5% [95% CI: 2.6-24.9%] versus. 36.5% [95% CI: 23.6-49.5%], P = .0126). These results demonstrate the efficacy of letermovir in decreasing the rates of clinically significant CMV infection in patients undergoing alemtuzumab T-cell depleted allo-HSCT.
Keywords: Alemtuzumab; Allogeneic hematopoietic cell transplant; Cytomegalovirus; Letermovir

Shorter vs. standard-duration antibiotic therapy for nocardiosis: a multi-center retrospective cohort study - Attias, Nofar Hezkelo; Schlaeffer-Yosef, Tal; Zahavi, Itay; Hasson, Noga; Ari, Yaara Ben; Darawsha, Basel; Levitan, Idan; Goldberg, Elad; Landes, Michal; Litchevsky, Vladislav; Ben-Zvi, Haim; Amit, Sharon; et al. (Infection, 2024)
The prolonged treatment recommended for nocardiosis does not rely on strong evidence. Consequently, some clinicians opt shorter therapy in certain circumstances. We assessed the effectiveness of shorter therapy.
Keywords: Immune suppression; Nocardia; Opportunistic infections; Treatment

Antigen Titers in Cryptococcal Meningitis: What Determines How Fast They Fall? - Bennett, John E; Williamson, Peter R (The Journal of Infectious Diseases, 2024)
Abstract Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for >1 year in serum from 38 of 44 (86%) patients and in cerebrospinal fluid (CSF) from 20 of 31 patients (67%), far beyond the time of culture conversion. The speed of titer decline, measured as the number of days for a 2-fold drop in titer to occur, was slower in serum than in CSF. The speed of decline of antigen titers was much slower in serum and CSF for patients infected with Cryptococcus gattii than Cryptococcus neoformans. The speed of decline in CSF and serum titers was also much slower in patients who had received a ventriculoperitoneal shunt for increased intracranial pressure. The variable and extraordinarily slow rate of clearance in our patients did not appear to reflect differences in disease control but rather differences in species and shunting for increased intracranial pressure.

Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement - Nelson, Zachary; Tarık Aslan, Abdullah; Beahm, Nathan P.; Blyth, Michelle; Cappiello, Matthew; Casaus, Danielle; Dominguez, Fernando; Egbert, Susan; Hanretty, Alexandra; Khadem, Tina; Olney, Katie; Abdul-Azim, Ahmed; et al. (JAMA Network Open, 2024)
Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence.To create a clinical guideline for the diagnosis and management of urinary tract infections 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 May 2023, new and existing members were solicited for questions on urinary tract infection prevention, diagnosis, and management. For each topic, literature searches were conducted up until early 2024 in any language. 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 developed discussing the available literature and associated risks and benefits of various approaches.A total of 54 members representing 12 countries reviewed 914 articles and submitted information relevant to 5 sections: prophylaxis and prevention (7 questions), diagnosis and diagnostic stewardship (7 questions), empirical treatment (3 questions), definitive treatment and antimicrobial stewardship (10 questions), and special populations and genitourinary syndromes (10 questions). Of 37 unique questions, a clear recommendation could be provided for 6 questions. In 3 of the remaining questions, a clear recommendation could only be provided for certain aspects of the question. Clinical reviews were generated for the remaining questions and aspects of questions not meeting criteria for a clear recommendation.In this consensus statement that applied the WikiGuidelines method for clinical guideline development, the majority of topics relating to prevention, diagnosis, and treatment of urinary tract infections lack high-quality prospective data and clear recommendations could not be made. Randomized clinical trials are underway to address some of these gaps; however further research is of utmost importance to inform true evidence-based, rather than eminence-based practice.

Prevention and Treatment of Cancer-Related Infections, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology - Baden, Lindsey Robert; Swaminathan, Sankar; Almyroudis, Nikolaos G.; Angarone, Michael; Baluch, Aliyah; Barros, Nicolas; Buss, Brian; Cohen, Stuart; Cooper, Brenda; Chiang, Augusto Dulanto; Boghdadly, Zeinab El; Gregg, Kevin; et al. (2024)
There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy. The NCCN Guidelines for the Prevention and Treatment of Cancer-Related Infections address infection concerns that may be observed in these immunocompromised populations and characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This paper highlights 2 recently updated sections of the guidelines, namely, infection concerns related to CAR T-cell therapy and antimicrobial prophylaxis recommendations, including vaccination, in patients at high-risk for infections.

Evaluation of Primary Oral Vancomycin Prophylaxis Against Clostridioides difficile Infection During Autologous Stem Cell Transplantation - Williams, Michael J; Atienza, Sol; Franzen, Erin; Rathod, Heena; Mejaki, Brittany; Graff, Justin; Korman, Sandra; Zouine, Noah; Gul, Zartash; Sana, Sherjeel; Medlin, Stephen; Buggy, Brian P (Open Forum Infectious Diseases, 2024)
Evaluations of oral vancomycin prophylaxis (OVP) against Clostridioides difficile have been reported in stem cell transplant populations with short follow-up periods. The longest known duration of standardized follow-up post-OVP is 90 days within an allogeneic stem cell transplant population. In 2017, we implemented OVP 125 mg twice daily in autologous stem cell transplant (ASCT) recipients beginning the day of admission and continued until the day of discharge.Patients who received an ASCT within our institution between 1 January 2012 and 31 December 2021 were included and separated into 2 groups based on the receipt of OVP. The primary study aim was to measure the incidence of C difficile infection (CDI) during the ASCT admission. A secondary aim was to evaluate for delayed CDI 180 days post-discharge. Other factors evaluated were prior history of CDI, use of systemic antimicrobials, and length of stay.Overall, 254 patients were evaluated and 58% received OVP, predominantly as primary prophylaxis (95%). Of the 18 patients who developed in-hospital CDI, 6 were in the OVP group versus 12 in the non-OVP cohort (4% vs 11%, P = .03). In the 180-day follow-up period, OVP use did not increase risk of developing CDI after discontinuation while in-hospital length of stay was identified as a significant factor.The use of OVP significantly reduced the incidence of CDI during the in-hospital ASCT course without increasing CDI post-OVP use. These encouraging results should promote further research into the use of OVP in ASCT.

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomised, multicentre, open-label, superiority clinical trial - Laporte-Amargos, Julia; Carmona-Torre, Francisco; Huguet, Maria; Puerta-Alcalde, Pedro; Rigo-Bonnin, Raul; Ulldemolins, Marta; Arnan, Montserrat; Pozo, Jose Luis del; Torrent, Anna; Garcia-Vidal, Carolina; Pallarès, Natàlia; Tebé, Cristian; et al. (Clinical Microbiology and Infection, 2024)
Keywords: Cefepime; Extended infusion; Febrile neutropenia; Meropenem; Piperacillin-tazobactam; Randomised controlled trial; β-lactam antibiotics

Safety of Kidney Transplantation from Donors with HIV - Durand, Christine M.; Massie, Allan; Florman, Sander; Liang, Tao; Rana, Meenakshi M.; Friedman-Moraco, Rachel; Gilbert, Alexander; Stock, Peter; Mehta, Sapna A.; Mehta, Shikha; Stosor, Valentina; Pereira, Marcus R.; et al. (New England Journal of Medicine, 2024)
BACKGROUND Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.)

B6: ALLOGENEIC AND AUTOLOGOUS DONOR SELECTION, EVALUATION, AND MANAGEMENT (FACT-JACIE International Standards for HEMATOPOIETIC CELLULAR THERAPY Product Collection, Processing, and Administration, 2024)

FACT-JACIE International Standards for HEMATOPOIETIC CELLULAR THERAPY Product Collection, Processing, and Administration (2024)

Outcomes of Haploidentical Stem Cell Transplant Recipients With HHV-6B Reactivation - Handley, Guy; Yepes, Amanda; Eliassen, Eva; Dominguez, Gabriel; Pasikhova, Yanina; Klinkova, Olga; Baluch, Aliyah; Febres-Aldana, Anthony J; Alsina, Melissa; Elmariah, Hany; Khimani, Farhad; Hansen, Doris K; et al. (Open Forum Infectious Diseases, 2024)
Human herpesvirus 6B (HHV-6B) frequently reactivates following allogeneic stem cell transplant (alloHCT). Consensus guidelines note that haploidentical alloHCT may represent a high-risk population for which there is little evidence; this warrants further investigation.In this single-center retrospective study, we evaluated 188 consecutive adult patients receiving haploidentical alloHCT between 11/2014 and 11/2020 and compared outcomes between patients with HHV-6B reactivation receiving targeted antiviral therapy and those who were clinically observed.Of the 58 included patients, 21 (36.2%) received antiviral therapy for HHV-6B reactivation with foscarnet (n = 19) or ganciclovir (n = 2). There were no differences in patient or disease characteristics between treated and observed patients. Treated patients were more likely to have high-level DNAemia (85.7% vs 40.5%; P < .001) and had higher peak viral quantitative measurements (median log10, 4.65 vs 3.84; P < .001). The median time to clearance from plasma (interquartile range) was 13 (7.25–20.00) days for all patients and was not significantly different between groups. There were no differences in episodes of encephalitis, grade III/IV acute graft-vs-host disease (GVHD), or time to neutrophil or platelet engraftment among treated vs observed patients. Day 100 nonrelapse mortality was not significantly different in the multivariate analysis; however, the presence of central nervous system symptoms was strongly associated with worse survival (hazard ratio, 4.11; 95% CI, 1.27–13.34; P = .018).We did not observe a difference in clinical outcomes between the treated and observed groups of patients with HHV-6B reactivation following haploidentical alloHCT. With the rising use of haploidentical transplant and post-transplant cyclophosphamide GVHD prevention platforms, prospective studies are needed to further characterize the risk and outcomes associated with HHV-6B reactivation and therapy.

Clinical Features, Diagnostics, Etiology, and Outcomes of Hospitalized Solid Organ Recipients With Community-Acquired Pneumonia: A Retrospective Cohort Analysis - Joean, Oana; Eynern, Laura Petra von; Welte, Tobias; Einecke, Gunilla; Dettmer, Sabine; Fuge, Jan; Taubert, Richard; Wedemeyer, Heiner; Rademacher, Jessica (CHEST, 2024)
Background Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation. Research Question What is the acute and long-term morbidity and mortality after CAP in organ transplant recipients? Study Design and Methods We retrospectively analyzed hospitalizations for CAP in solid organ recipients at the largest German transplant center. The study included patients admitted between January 1, 2010, and May 31, 2021. The reported outcomes are in-hospital and 1-year mortality, risk of cardiovascular events during hospitalization and at 1 year, admission to the ICU, and risk of pneumonia with Pseudomonas aeruginosa. Multivariable binary logistic regression using stepwise forward selection was performed to determine predictive factors for pneumonia with P aeruginosa. Results We analyzed data from 403 hospitalizations of 333 solid organ recipients. In > 60% of cases, patients had multiple comorbidities, with cardiovascular and chronic kidney disease being the most prevalent. More than one-half of the patients required oxygen supplementation after admission. In-hospital mortality (13.2%) and the death rate at 1 year postevent (24.6%) were higher than data reported from immunocompetent patients. We also observed high rates of acute cardiovascular events and events occurring 1 year after admission. Early blood cultures and bronchoscopy in the first 24 h significantly increased the odds of establishing an etiology. In our low-resistance setting, the burden of antimicrobial resistance was driven by bacteria from chronically colonized patients, mostly lung transplant recipients. Interpretation This comprehensive analysis highlights the high morbidity associated with CAP after transplantation. It also emphasizes the need for prospective multicenter studies to guide evidence-based practices and improve outcomes for these vulnerable patients.

International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates—2024 - Peled, Yael; Ducharme, Anique; Kittleson, Michelle; Bansal, Neha; Stehlik, Josef; Amdani, Shahnawaz; Saeed, Diyar; Cheng, Richard; Clarke, Brian; Dobbels, Fabienne; Farr, Maryjane; Lindenfeld, JoAnn; et al. (The Journal of Heart and Lung Transplantation, 2024)
Keywords: Collaborative treatment; Durable mechanical circulatory support; Guideline-directed medical therapy; Heart transplant candidates; Pediatric heart transplant

Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection - Chou, Sunwen; Winston, Drew J; Avery, Robin K; Cordonnier, Catherine; Duarte, Rafael F; Haider, Shariq; Maertens, Johan; Peggs, Karl S; Solano, Carlos; Young, Jo-Anne H; Gu, Joan; Pocock, Ginger; et al. (The Journal of Infectious Diseases, 2024)
Abstract Background Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively. Development of maribavir and ganciclovir resistance was compared after receiving either drug. Methods Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment. Results Prior antiviral drug exposure was limited, with only 2 instances of baseline drug resistance detected. An equal number (n=241) received valganciclovir or maribavir for at least 21 days (median 55-56 days). Among them, drug resistance mutations were detected in 24 (10%) maribavir recipients at 35-125 days (median 56) after starting therapy, including in 12 of 14 who experienced a viral load rebound while on therapy. Ganciclovir resistance mutations developed in 6 (2.5%) valganciclovir recipients at 66-110 days (median 90). One maribavir recipient developed a novel UL97 gene mutation (P-loop substitution G343A) that conferred strong maribavir and ganciclovir resistance in vitro. Viral clearance was confirmed in 17 (74%) of 23 patients with emergent maribavir resistance after re-treatment with an alternative CMV antiviral drug. Conclusion After 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy. Clinical Trials Registration NCT02927067 (AURORA)

Transplantid.net Journal Club: August 2024 - Barros, Nicolas; Vergidis, Paschalis (2024)
Commentary on https://transplantid.net/J9D9FTF2

Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections - Tamma, Pranita D; Heil, Emily L; Justo, Julie Ann; Mathers, Amy J; Satlin, Michael J; Bonomo, Robert A (Clinical Infectious Diseases, 2024)
The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant (AMR) infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β- lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document.A panel of six infectious diseases specialists with expertise in managing antimicrobial- resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of AMR and availability of specific anti-infectives internationally, this document focuses on the treatment of AMR infections in the United States.Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults.The field of AMR is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of AMR infections. This document is current as of December 31, 2023 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Transplantid.net Journal Club: July 2024 - Barros, Nicolas; Vergidis, Paschalis (transplantid.net, 2024)
Commentary on https://transplantid.net/LBN3S68N

Consensus Definitions of Cytomegalovirus (CMV) Infection and Disease in Transplant Patients Including Resistant and Refractory CMV for Use in Clinical Trials: 2024 Update From the Transplant Associated Virus Infections Forum - Ljungman, Per; Chemaly, Roy F; Khawaya, Fareed; Alain, Sophie; Avery, Robin; Badshah, Cyrus; Boeckh, Michael; Fournier, Martha; Hodowanec, Aimee; Komatsu, Takashi; Limaye, Ajit P; Manuel, Oriol; et al. (Clinical Infectious Diseases, 2024)
Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work.

Adenovirus infections after allogeneic hematopoietic cell transplantation in children and adults: a study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation - Styczynski, Jan; Tridello, Gloria; Knelange, Nina; Wendel, Lotus; Ljungman, Per; Mikulska, Malgorzata; Gil, Lidia; Cesaro, Simone; Averbuch, Diana; von dem Borne, Peter; Xhaard, Aliénor; Mielke, Stephan; et al. (Bone Marrow Transplantation, 2024)
The objective of the study was the analysis of clinical types, outcomes, and risk factors associated with the outcome of adenovirus (ADV) infection, in children and adults after allo-HCT. A total number of 2529 patients (43.9% children; 56.1% adults) transplanted between 2000 and 2022 reported to the EBMT database with diagnosis of ADV infection were analyzed. ADV infection manifested mainly as viremia (62.6%) or gastrointestinal infection (17.9%). The risk of 1-year mortality was higher in adults (p = 0.0001), and in patients with ADV infection developing before day +100 (p < 0.0001). The 100-day overall survival after diagnosis of ADV infections was 79.2% in children and 71.9% in adults (p < 0.0001). Factors contributing to increased risk of death by day +100 in multivariate analysis, in children: CMV seropositivity of donor and/or recipient (p = 0.02), and Lansky/Karnofsky score <90 (p < 0.0001), while in adults: type of ADV infection (viremia or pneumonia vs gastrointestinal infection) (p = 0.0004), second or higher HCT (p = 0.0003), and shorter time from allo-HCT to ADV infection (p = 0.003). In conclusion, we have shown that in patients infected with ADV, short-term survival is better in children than adults. Factors directly related to ADV infection (time, clinical type) contribute to mortality in adults, while pre-transplant factors (CMV serostatus, Lansky/Karnofsky score) contribute to mortality in children.
Keywords: Risk factors; Stem-cell research

Guidelines for the Prevention, Diagnosis, Care and Treatment for People with Chronic Hepatitis B Infection (Text Extract): Executive Summary (Infectious Diseases & Immunity, 2024)

SARS-CoV-2 PCR Cycle Threshold Trends in Immunocompromised Patients and Implications for Isolation Precautions - Harris, Courtney E; Vaidya, Vineeta; Lan, Zhou; Klompas, Michael; Rhee, Chanu; Baden, Lindsey; Baker, Meghan A (Open Forum Infectious Diseases, 2024)
Among 495 immunocompromised patients positive for SARS-CoV-2, PCR cycle thresholds remained <33 beyond 20 days more frequently in patients with hematologic malignancies, particularly those receiving B-cell depleting or BTKi therapy, compared to those with solid organ malignancy (26% vs 5%).

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients - Foca, Marc; Demirhan, Salih; Munoz, Flor M; Valencia Deray, Kristen G; Bocchini, Claire E; Sharma, Tanvi S; Sherman, Gilad; Muller, William J; Heald-Sargent, Taylor; Danziger-Isakov, Lara; Blum, Samantha; Boguniewicz, Juri; et al. (Open Forum Infectious Diseases, 2024)
Abstract Background Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Therapeutic Myths in Solid Organ Transplantation Infectious Diseases - Goodlet, Kellie J; McCreary, Erin K; Nailor, Michael D; Barnes, Darina; Brokhof, Marissa M; Bova, Sarah; Clemens, Evan; Kelly, Beth; Lichvar, Alicia; Pluckrose, Dawn M; Summers, Bryant B; Szempruch, Kristen R; et al. (Open Forum Infectious Diseases, 2024)
Abstract Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic “myths” may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population.

Cryptococcosis Associated With Biologic Therapy: A Narrative Review - Li, Xin; Paccoud, Olivier; Chan, Koon-Ho; Yuen, Kwok-Yung; Manchon, Romain; Lanternier, Fanny; Slavin, Monica A; Van De Veerdonk, Frank L; Bicanic, Tihana; Lortholary, Olivier (Open Forum Infectious Diseases, 2024)
Abstract Cryptococcus is an opportunistic fungal pathogen that can cause disseminated infection with predominant central nervous system involvement in patients with compromised immunity. Biologics are increasingly used in the treatment of neoplasms and autoimmune/inflammatory conditions and the prevention of transplant rejection, which may affect human defense mechanisms against cryptococcosis. In this review, we comprehensively investigate the association between cryptococcosis and various biologics, highlighting their risks of infection, clinical manifestations, and clinical outcomes. Clinicians should remain vigilant for the risk of cryptococcosis in patients receiving biologics that affect the Th1/macrophage activation pathways, such as tumor necrosis factor α antagonists, Bruton tyrosine kinase inhibitors, fingolimod, JAK/STAT inhibitors (Janus kinase/signal transducer and activator of transcription), and monoclonal antibody against CD52. Other risk factors—such as age, underlying condition, and concurrent immunosuppressants, especially corticosteroids—should also be taken into account during risk stratification.

Real-World Experience With Maribavir for Treatment of Cytomegalovirus Infection in High-Risk Solid Organ Transplant Recipients - Ni, Bin; Wolfe, Cameron R; Arif, Sana; Carugati, Manuela; Heldman, Madeleine R; Messina, Julia A; Miller, Rachel A; Saullo, Jennifer L; Baker, Arthur W; Maziarz, Eileen K (Open Forum Infectious Diseases, 2024)
Abstract We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.

Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis - Brown, Lottie; Rautemaa-Richardson, Riina; Mengoli, Carlo; Alanio, Alexandre; Barnes, Rosemary A; Bretagne, Stéphane; Chen, Sharon C A; Cordonnier, Catherine; Donnelly, J Peter; Heinz, Werner J; Jones, Brian; Klingspor, Lena; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2024)
This meta-analysis demonstrated very high diagnostic performance of PCR assays when used as screening tests for Pneumocystis pneumonia in high-risk patient groups, regardless of HIV status. qPCR on bronchoalveolar lavage fluid samples provided optimal sensitivity, closely followed by qPCR on induced sputum, while also providing adequate specificity., Graphical abstractThis graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/pcr-on-respiratory-tract-specimens-of-immunocompromised-patients-to-diagnose-pneumocystosis-pcp-a-systematic-review-and-meta-analysis-89aa7a50-efbc-4ebb-8f20-c17d207e8d8e?utm_campaign=tidbitlinkshare&utm_source=ITP

The Burden of Invasive Fungal Disease Following Chimeric Antigen Receptor T-Cell Therapy and Strategies for Prevention - Little, Jessica S; Kampouri, Eleftheria; Friedman, Daniel Z; McCarty, Todd; Thompson, George R; Kontoyiannis, Dimitrios P; Vazquez, Jose; Baddley, John W; Hammond, Sarah P (Open Forum Infectious Diseases, 2024)
Abstract Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy approved for the treatment of hematologic malignancies. This therapy leads to a variety of immunologic deficits that could place patients at risk for invasive fungal disease (IFD). Studies assessing IFD in this setting are limited by inconsistent definitions and heterogeneity in prophylaxis use, although the incidence of IFD after CAR T-cell therapy, particularly for lymphoma and myeloma, appears to be low. This review evaluates the incidence of IFD after CAR T-cell therapy, and discusses optimal approaches to prevention, highlighting areas that require further study as well as future applications of cellular therapy that may impact IFD risk. As the use of CAR T-cell therapy continues to expand for hematologic malignancies, solid tumors, and most recently to include non-oncologic diseases, understanding the risk for IFD in this uniquely immunosuppressed population is imperative to prevent morbidity and mortality.

An Unexpectedly High Incidence of Invasive Fungal Diseases in Solid Organ Transplant Recipients Taking Belatacept for Organ Rejection Prophylaxis: A Single-Center Retrospective Cohort Study - Bell, Elizabeth; Pisano, Jennifer; Brown, Manasa; Friedman, Daniel (Open Forum Infectious Diseases, 2024)
Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and candidiasis (22%). The infected cohort was more likely to receive basiliximab, undergo lung transplantation, or identify as White. Higher rates of aspergillosis were seen in this lung cohort than previously reported.

AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis - Karvellas, Constantine J.; Bajaj, Jasmohan S.; Kamath, Patrick S.; Napolitano, Lena; O’Leary, Jacqueline G.; Solà, Elsa; Subramanian, Ram; Wong, Florence; Asrani, Sumeet K. (Hepatology, 2024)
An abstract is unavailable.

Donor-derived carbapenem-resistant gram-negative bacterial infections in solid organ transplant recipients: Active surveillance enhances recipient safety - Mularoni, Alessandra; Cona, Andrea; Campanella, Maria; Barbera, Floriana; Medaglia, Alice Annalisa; Cervo, Adriana; Cuscino, Nicola; Di Mento, Giuseppina; Graziano, Elena; El Jalbout, Jana Dib; Alduino, Rossella; Tuzzolino, Fabio; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2024)
Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile.
Keywords: Adult; Aged; Anti-Bacterial Agents; Carbapenems; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Incidence; Male; Middle Aged; Organ Transplantation; Postoperative Complications; Prognosis; Prospective Studies; Risk Factors; Tissue Donors; Transplant Recipients; active surveillance system; carbapenem-resistant gram-negative bacteria; donor-derived infection; multidrug-resistant organism; risk mitigation strategy; solid organ transplant

Invasive Aspergillosis in Liver Transplant Recipients in The Current Era - Kimura, Muneyoshi; Rinaldi, Matteo; Kothari, Sagar; Giannella, Maddalena; Anjan, Shweta; Natori, Yoichiro; Phoompoung, Pakpoom; Gault, Emily; Hand, Jonathan; D'Asaro, Matilde; Neofytos, Dionysios; Mueller, Nicolas J.; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2024)
Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.
Keywords: invasive aspergillosis; liver transplantation; targeted antifungal prophylaxis

Reactivation of a Transplant Recipient's Inherited Human Herpesvirus 6 and Implications to the Graft - Hannolainen, Leo; Pyöriä, Lari; Pratas, Diogo; Lohi, Jouko; Skuja, Sandra; Rasa-Dzelzkaleja, Santa; Murovska, Modra; Hedman, Klaus; Jahnukainen, Timo; Perdomo, Maria Fernanda (The Journal of Infectious Diseases, 2024)
Abstract Background The implications of inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) in solid organ transplantation remain uncertain. Although this trait has been linked to unfavorable clinical outcomes, an association between viral reactivation and complications has only been conclusively established in a few cases. Methods We used hybrid capture sequencing for in-depth analysis of the viral sequences reconstructed from sequential liver biopsies. Moreover, we investigated viral replication through in situ hybridization (U38–U94 genes), reverse transcriptase polymerase chain reaction (U89/U90 genes), immunohistochemistry, and immunofluorescence. We also performed whole transcriptome sequencing to profile the host immune response. Results We report a case of reactivation of a recipient’s iciHHV-6B and subsequent infection of the graft. Using a novel approach integrating the analysis of viral and mitochondrial DNAs, we located the iciHHV-6B intragraft. We demonstrated active replication via the emergence of viral minor variants, in addition to positive viral messenger RNAs and antigen stainings in tissue sections. Furthermore, we detected significant upregulation of antiviral immune responses, arguing against immunotolerance. Conclusions Our analysis underscores the potential pathological impact of iciHHV-6B, emphasizing the need for monitoring reactivation in transplant recipients. Most crucially, it highlights the critical role that the host's virome can play in shaping the outcome of transplantation.

CMV-RNAemia as new marker of active viral replication in transplant recipients - Piccirilli, Giulia; Lanna, Federica; Gabrielli, Liliana; Motta, Vincenzo; Franceschiello, Martina; Cantiani, Alessia; Pavoni, Matteo; Leone, Marta; Borgatti, Eva Caterina; Gibertoni, Dino; Pascale, Renato; Giannella, Maddalena; et al. (Journal of Clinical Microbiology, 2024)

Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial - Chandraker, Anil; Regmi, Anil; Gohh, Reginald; Sharma, Akhil; Woodle, E. Steve; Ansari, Mohammed J.; Nair, Vinay; Chen, Ling-Xin; Alhamad, Tarek; Norman, Silas; Cibrik, Diane; Singh, Manpreet; et al. (Journal of the American Society of Nephrology, 2024)
Key Points Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo. BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients. The presence and persistence of posoleucel was confirmed by T-cell receptor variable β sequencing. Background Kidney transplant recipients with BK virus infection are at risk of developing BK virus–associated nephropathy, allograft rejection, and subsequent graft loss. There are no approved treatments for BK virus infection. Posoleucel is an off-the-shelf, allogeneic, multivirus-specific T-cell investigational therapy targeting BK virus, as well as five other opportunistic viruses: adenovirus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6, and John Cunningham virus. Methods In this phase 2, double-blind study, kidney transplant recipients with BK viremia were randomized 1:1:1 to receive posoleucel weekly for 3 weeks and then every 14 days (bi-weekly dosing) or every 28 days (monthly dosing) or placebo for 12 weeks. Participants were followed for 12 weeks after completing treatment. The primary objective was safety; the secondary objective was plasma BK viral load reduction. Results Sixty-one participants were randomized and dosed. Baseline characteristics were similar across groups. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. The proportion of patients who had adverse events (AEs) judged by the investigators to be treatment-related was slightly lower in recipients of posoleucel: 20% (4 of 20 patients) and 18% (4 of 22) in those infused on a bi-weekly and monthly schedule, respectively, and 26% (5 of 19) in placebo recipients. None of the grade 3–4 AEs or serious AEs in any group were deemed treatment-related. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. Three participants had allograft rejection, but none were deemed treatment-related by investigators. In posoleucel recipients, BK viremia reduction was associated with an increase in the circulating frequency of BK virus–specific T cells, and the presence and persistence of posoleucel was confirmed by T-cell receptor sequencing. Conclusions Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared with placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes. Clinical Trial registry name and registration number: Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia, NCT04605484. Visual Abstract Export

AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis - Kaplan, David E.; Ripoll, Cristina; Thiele, Maja; Fortune, Brett E.; Simonetto, Douglas A.; Garcia-Tsao, Guadalupe; Bosch, Jaime (Hepatology, 2024)
An abstract is unavailable.

Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant - Khoury, Ruby; Grimley, Michael S.; Nelson, Adam S.; Leemhuis, Tom; Cancelas, Jose A.; Cook, Eleanor; Wang, YunZu; Heyenbruch, Daria; Bollard, Catherine M.; Keller, Michael D.; Hanley, Patrick J.; Lutzko, Carolyn; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2024)
Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients.
Keywords: BK; CMV; EBV; PTLD; adenovirus; solid organ transplant; viral reactivation; virus-specific T cells

Live-Attenuated Vaccines in Pediatric Solid Organ Transplant - Hartley, Christopher; Thomas, Tina; Smith, Sara Kathryn; Karnsakul, Wikrom (Vaccines, 2024)
Measles, mumps, rubella (MMR), and varicella incidence rates have increased due to the delayed vaccination schedules of children secondary to the COVID-19 pandemic. Decreased herd immunity creates a risk for immunocompetent children and immunocompromised individuals in the community. Historically, live-attenuated vaccines (MMR and varicella) were recommended before solid organ transplants. The amount of time before transplant when this is appropriate is often debated, as is the utility of vaccine titers. MMR and varicella vaccines previously were not recommended in immunocompromised patients post-solid organ transplant due to the undue risk of transmission and posed infection risk. The new literature on live-attenuated vaccines in post-transplant pediatric patients provides more insight into the vaccines’ safety and efficacy. The present article aims to provide guidance on live-attenuated vaccines (MMR and varicella) in the pre-transplant and post-operative solid organ transplant phases of care in pediatric patients.

Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring - Mikulska, Malgorzata; Melchio, Monica; Signori, Alessio; Ullah, Nadir; Miletich, Franca; Sepulcri, Chiara; Limongelli, Alessandro; Giacobbe, Daniele Roberto; Balletto, Elisa; Russo, Chiara; Magnasco, Laura; Vena, Antonio; et al. (Journal of Antimicrobial Chemotherapy, 2024)
Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU. The aim was to compare isavuconazole levels between critically ill and non-critically ill patients.Retrospective analysis of data from all patients treated with standard-dose isavuconazole between 1 January 2019 and 26 October 2022 was performed. The following data were collected: TDM results from the first 30 days of therapy; ward of admission; demographic and clinical characteristics; continuous renal replacement therapy; extracorporeal membrane oxygenation; and co-administered drugs.Seventy-two patients (median age 65 years) and 188 TDM measurements (mean number of samples per patient 2.6 ± 1.7) were included; 33 (45.8%) were ICU patients (3 also had haematological disorders); 39 (54.2%) were non-ICU patients, of whom 31 had haematological disorders. In all patients, the mean isavuconazole blood level was 3.33 ± 2.26 mg/L. Significantly lower levels were observed in the ICU versus the non-ICU population: mean 2.02 ± 1.22 versus 4.15 ± 2.31 mg/L (P < 0.001). Significantly higher rates of subtherapeutic levels were observed in ICU patients compared with the non-ICU population: all determinations <2 mg/L in 33.3% versus 7.7%, and all determinations <1 mg/L in 12.1% versus 0%, respectively. Predictors of lower isavuconazole levels were admission to the ICU, BMI > 25 kg/m2, bilirubin > 1.2 mg/dL and the absence of haematological disorder.ICU patients had significantly lower isavuconazole blood levels compared to non-ICU population. The TDM of isavuconazole for efficacy should be performed in ICU.

Risk factors, management, and clinical outcomes of invasive Mycoplasma and Ureaplasma infections after lung transplantation - Tam, Patrick C. K.; Hardie, Rochelle; Alexander, Barbara D.; Yarrington, Michael E.; Lee, Mark J.; Polage, Chris R.; Messina, Julia A.; Maziarz, Eileen K.; Saullo, Jennifer L.; Miller, Rachel; Wolfe, Cameron R.; Arif, Sana; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2024)
Mollicute infections, caused by Mycoplasma and Ureaplasma species, are serious complications after lung transplantation; however, understanding of the epidemiology and outcomes of these infections remains limited. We conducted a single-center retrospective study of 1156 consecutive lung transplants performed from 2010-2019. We used log-binomial regression to identify risk factors for infection and analyzed clinical management and outcomes. In total, 27 (2.3%) recipients developed mollicute infection. Donor characteristics independently associated with recipient infection were age ≤40 years (prevalence rate ratio [PRR] 2.6, 95% CI 1.0-6.9), White race (PRR 3.1, 95% CI 1.1-8.8), and purulent secretions on donor bronchoscopy (PRR 2.3, 95% CI 1.1-5.0). Median time to diagnosis was 16 days posttransplant (IQR: 11-26 days). Mollicute-infected recipients were significantly more likely to require prolonged ventilatory support (66.7% vs 21.4%), undergo dialysis (44.4% vs 6.3%), and remain hospitalized ≥30 days (70.4% vs 27.4%) after transplant. One-year posttransplant mortality in mollicute-infected recipients was 12/27 (44%), compared to 148/1129 (13%) in those without infection (P <.0001). Hyperammonemia syndrome occurred in 5/27 (19%) mollicute-infected recipients, of whom 3 (60%) died within 10 weeks posttransplant. This study highlights the morbidity and mortality associated with mollicute infection after lung transplantation and the need for better screening and management protocols.
Keywords: Adult; Humans; Lung Transplantation; Mycoplasma; Mycoplasma species; Retrospective Studies; Risk Factors; Ureaplasma Infections; Ureaplasma species; lung transplantation; mollicute infection

Presentation, management, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study - Callegari, Michelle; Danziger‐Isakov, Lara A.; Rose, Anne; Kaul, Daniel; Shaffer, Kelly; Chong, Pearlie P.; Florescu, Diana; German, Kaci; Avery, Robin; Nguyen, M. Hong; Wildfeuer, Brett; Michaels, Marian G.; et al. (Transplant Infectious Disease, 2024)
Background: Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients. Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients.

Concurrent JCPyV-DNAemia Is Correlated With Poor Graft Outcome in Kidney Transplant Recipients with Polyomavirus-associated Nephropathy - Zhang, Hui; Luo, Jin-Quan; Zhao, Guo-Dong; Huang, Yang; Yang, Shi-Cong; Chen, Pei-Song; Li, Jun; Wu, Cheng-Lin; Qiu, Jiang; Chen, Xu-Tao; Huang, Gang (Transplantation, 2024)
Background. Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN). Methods. A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated. Results. The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P = 0.031). Kaplan–Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival. Conclusions. Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.

Emerging Role of Plasma Microbial Cell-free DNA in the Diagnosis of Pediatric Mucormycosis - Gracia, Michael; Hadley, Emma; Ramchandar, Nanda; Coufal, Nicole G. (Pediatric Infectious Disease Journal, 2024)
Mucormycosis is a rare and devastating angioinvasive infection that can be challenging to diagnose due to the low sensitivity of current noninvasive diagnostics and the lack of a “gold standard” reference test. We describe a retrospective case series of children with suspected mucormycosis where plasma microbial cell-free DNA testing was utilized in the diagnostic evaluation to illustrate the ways in which microbial cell-free DNA testing can noninvasively contribute to the evaluation and management of at-risk, immunosuppressed patients suspected of mucormycosis.

New treatment options for critically important WHO fungal priority pathogens - Kriegl, Lisa; Egger, Matthias; Boyer, Johannes; Hoenigl, Martin; Krause, Robert (Clinical Microbiology and Infection, 2024)

Atypical pneumonia testing in transplant recipients - Feller, Fionna; Trubin, Paul; Malinis, Maricar; Vogel, Joshua S.; Merwede, Jacob; Peaper, David R.; Azar, Marwan M. (Transplant Infectious Disease, 2024)
Background: The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. Methods: A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. Results: Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. Conclusion: The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.

Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National Veterans Affairs Cohort - Chen, Ting-Yi; Jacob, David A; Coppin, John D; Jinadatha, Chetan (Open Forum Infectious Diseases, 2024)
Ibrutinib has been a first-line treatment for chronic lymphocytic leukemia since 2014. Case reports of hepatitis B virus (HBV) reactivation after ibrutinib initiation have been presented. The association between the risk of HBV reactivation and ibrutinib initiation remains unclear. This nationwide study aimed to estimate the incidence of HBV reactivation after ibrutinib initiation.This study included patients who received ibrutinib between 1 February 2014 and 31 October 2019. Possible reactivations were searched by (1) changes in HBV surface antigen or HBV DNA from no data or negative status to positive after ibrutinib initiation, (2) alanine aminotransferase levels that were at least 3 times the baseline value after ibrutinib initiation, and (3) new antiviral prescriptions against HBV after ibrutinib initiation. Individual chart reviews were conducted to identify HBV reactivation attributed to ibrutinib. The cumulative incidence of HBV reactivation was calculated.A total 4130 patients were eligible during the study period. Of these, patients with negative HBV core antibody (anti-HBcAb; n = 1670) and patients who were taking antivirals against HBV (n = 60) were excluded. There were 2219 patients without anti-HBcAb testing results. Among the remaining 181 patients with positive anti-HBcAb, 7 HBV reactivations were directly attributable to ibrutinib treatment after chart review, for a 3.9% cumulative incidence.Our study revealed a low cumulative incidence of HBV reactivation after ibrutinib initiation among patients with previous anti-HBcAb positivity, indicating a moderate risk of HBV reactivation.

Serial Bronchoalveolar Lavage Fluid Aspergillus Galactomannan and Treatment Response in Invasive Pulmonary Aspergillosis - Friedman, Daniel Z P; Theel, Elitza S; Walker, Randall C; Vikram, Holenarasipur R; Razonable, Raymund R; Vergidis, Paschalis (Open Forum Infectious Diseases, 2024)
Abstract We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response.

Epidemiological Characteristics and Outcome of Viral Respiratory Tract Infections in the First Year After Allogeneic Hematopoietic Cell Transplantation - Van Praet, Jens T; Huysman, Andreas; De Knijf, Eline; De Buyser, Stefanie; Snauwaert, Sylvia; Van Droogenbroeck, Jan; Lodewyck, Tom; Schauwvlieghe, Alexander; Selleslag, Dominik; Reynders, Marijke (The Journal of Infectious Diseases, 2024)
Abstract Adverse outcomes of viral respiratory tract infections (RTIs) have been reported in recipients of allogeneic hematopoietic cell transplantation. Using a laboratory-developed multiparameter polymerase chain reaction in a consecutive series of 242 patients, we found the highest incidence of viral RTI in the preengraftment phase. The occurrence of multiple episodes of viral RTI or viral pneumonia was significantly associated with a higher hazard of nonrelapse mortality in the first year after transplantation. We observed a 90-day mortality of 19.7% after viral RTI, which was significantly different between patient groups stratified according to the immunodeficiency scoring index.

The Burden and Impact of Early Post-transplant Multidrug-Resistant Organism Detection Among Renal Transplant Recipients, 2005–2021 - Babiker, Ahmed; Karadkhele, Geeta; Bombin, Andrei; Watkins, Rockford; Robichaux, Chad; Smith, Gillian; Beechar, Vivek B; Steed, Danielle B; Jacobs, Jesse T; Read, Timothy D; Satola, Sarah; Larsen, Christian P; et al. (Open Forum Infectious Diseases, 2024)
Abstract Background Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. Methods We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score–weighted sensitivity, and subgroup analyses were performed. Results Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%–1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31–0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21–8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92–55.5; subdistribution aHR, 7.15; 95% CI, 0.95–53.7). A similar trend was seen in the subgroup and sensitivity analyses. Conclusions MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.

Risk of Infective Endocarditis in Streptococcus mitis Bloodstream Infections Among Patients with Neutropenia from Hematologic Malignancies - Monk, Miranda; Patel, Nikitha R; Elshaboury, Ramy; Kubiak, David W; Hammond, Sarah P (Open Forum Infectious Diseases, 2024)
Abstract Streptococcus mitis commonly causes bloodstream infections (BSIs) in neutropenic patients but infrequently results in infective endocarditis (IE) in this population. Among 210 patients with neutropenia and S. mitis BSI, 55% underwent cardiac imaging. None were diagnosed with S. mitis IE; 3 had recurrent S. mitis BSI within 12 weeks.

Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis - Agudelo Higuita, Nelson Iván; Chastain, Daniel B; Scott, Brian; Sahra, Syeda; Vargas Barahona, Lilian; Henao Cordero, José; Lee, Alfred L H; Tuells, Jose; Henao-Martínez, Andrés F (Open Forum Infectious Diseases, 2024)

Impact of deceased organ donor marijuana use on donor culture positivity and solid organ transplant recipient outcomes - Moore, Krista; Lautenbach, Ebbing; Blumberg, Emily A.; Han, Jennifer; Lee, Dong Heun; Clauss, Heather; Hasz, Richard; Bilker, Warren B.; Molnar, Esther; Alimenti, Darcy; West, Sharon; Tolomeo, Pam; et al. (American Journal of Transplantation, 2024)
Keywords: CDC; CI; CRE; Centers for Disease Control and Prevention; DDI; DTAC; Disease Transmission Advisory Committee; ESBL; IFI; IQR; MDR; MDRO; MRSA; NHSN; National Healthcare Safety Network; OPO; OPTN; OR; Organ Procurement and Transplantation Network; PHS; Public Health Service; SOT; Spp; THC; VRE; aHR; aOR; adjusted hazard ratio; adjusted odds ratio; carbapenem-resistant Enterobacterales; confidence interval; donor-derived infection; extended-spectrum beta-lactamase; interquartile range; invasive fungal infection; methicillin-resistant Staphylococcus aureus; multidrug-resistant; multidrug-resistant organism; odds ratio; organ procurement organization; solid organ transplantation; species; tetrahydrocannabinol; vancomycin-resistant Enterococcus

Combination Antifungal Therapy for Invasive Mucormycosis in Immunocompromised Hosts: A Single-Center Experience - Lu, Brian; Ha, David; Shen, Sa; Ferguson Toll, Jessica; Kim, Ailin; Kim, Sarah; Mui, Emily; Deresinski, Stan; Holubar, Marisa; Alegria, William (Open Forum Infectious Diseases, 2024)
Abstract Combination antifungal therapy for invasive mucormycosis remains controversial and is inconsistently defined in prior studies. In a cohort of immunocompromised patients with invasive mucormycosis, we found no difference in 6-week mortality with upfront nor salvage combination therapy compared to monotherapy.

Histoplasmosis beyond HIV: Clinical characteristics and outcomes in non-HIV population - Tello-Mercado, A C; Martínez-Guerra, B; Román-Montes, C M; Seoane-Hernandez, L; Rangel-Cordero, A; Martínez-Gamboa, R A; Sifuentes-Osornio, J; Ponce-de-León, A; González Lara, M F; Niembro-Ortega, M D (Open Forum Infectious Diseases, 2024)
Histoplasmosis is an endemic and invasive mycosis caused by Histoplasma capsulatum. We conducted a retrospective study comparing non-HIV immunosuppressed patients with a historical cohort of HIV and histoplasmosis. We included 199 patients with proven or probable histoplasmosis, of which 25.1% were non-HIV. Diabetes mellitus, chronic kidney disease, hematologic neoplasms, rheumatologic diseases and transplants were more frequent among non-HIV patients (p<0.01). Death after diagnosis occurred in 44% patients. 44% of immunocompromised non-HIV patients died within the first 6-week period following their diagnosis. A high suspicion index for histoplasmosis should be kept in immunosuppressed patients.

Approach to febrile neutropenia in patients undergoing treatments for hematologic malignancies - Stohs, Erica J.; Abbas, Anum; Freifeld, Alison (Transplant Infectious Disease, 2024)
Febrile neutropenia (FN) is common among hematologic malignancy patients, including recipients of hematopoietic cell transplantation (HCT) and cellular therapies such as chimeric antigen receptor (CAR)-T-cell therapy. Prompt empiric antibiotic use has been the mainstay for decades but a “one-size-fits-all” approach is no longer broadly accepted, as treatment-related infectious risk are more understood. Growing antimicrobial resistance is an increasing clinical challenge. Evolving strategies on deescalation of broad-spectrum antibiotics in FN without identified infection are areas of particular interest.

Coccidioidomycosis and Histoplasmosis in Immunocompetent Persons - Galgiani, John N.; Kauffman, Carol A. (New England Journal of Medicine, 2024)

Do infectious diseases after kidney re-transplantation differ from those after first kidney transplantation? - Kusejko, Katharina; Neofytos, Dionysios; Van Delden, Christian; Hirsch, Hans H; Meylan, Pascal; Boggian, Katia; Hirzel, Cedric; Garzoni, Christian; Sidler, Daniel; Schnyder, Aurelia; Schaub, Stefan; Golshayan, Déla; et al. (Open Forum Infectious Diseases, 2024)
Abstract Background Infectious diseases (ID) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney re-transplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods We included adult patients with records on the f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients, and compared infection rates, causative pathogens and infection sites. Recurrent time to event analyses were performed for comparison of infection rates. Results A total of 59 patients with a median age of 47 years (range = 18 - 73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modelling, the rate of ID events was significantly lower after re-K-Tx (HR = 0.70, p = 0.02). More bacterial (68.9% versus 60.4%) and fungal (4.0% versus 1.1%) infections were observed after f-K-Tx, but less viral infections (27.0% versus 38.5%) as compared to after re-K-Tx (p = 0.11). After f-K-Tx, urinary tract and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (p < 0.001). Conclusions Infectious disease events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx compared to after re-K-Tx.

Clinical outcomes of baloxavir versus oseltamivir in immunocompromised patients - Ringer, Matthew; Malinis, Maricar; McManus, Dayna; Davis, Matthew; Shah, Sunish; Trubin, Paul; Topal, Jeffrey E.; Azar, Marwan M. (Transplant Infectious Disease, 2024)
Background: Neuraminidase inhibitors, including oseltamivir, are the treatment standard for influenza. Baloxavir, a novel antiviral, demonstrated comparable outcomes to oseltamivir in outpatients with influenza. Baloxavir was equally effective as oseltamivir in a retrospective study of hospitalized patients with influenza at our institution. However, the efficacy of baloxavir in immunocompromised patients is unclear. Methods: We conducted a retrospective cohort study of immunocompromised adult patients hospitalized with influenza A who received baloxavir from January 2019 to April 2019 or oseltamivir from January 2018 to April 2018. Demographic and clinical outcomes were assessed. Primary outcomes were time from antiviral initiation to resolution of hypoxia and fever. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) care, ICU LOS, and 30-day mortality. Results: Of 95 total patients, 52 received baloxavir and 43 received oseltamivir. Other than younger age (57.5 vs. 65; p = .035) and longer duration between vaccination and symptom onset (114 vs. 86 days; p = .001) in the baloxavir group, baseline characteristics did not differ. H1 was the predominant subtype in the baloxavir group (65.3%) versus H3 in the oseltamivir group (85.7%). When comparing baloxavir to oseltamivir, there was no significant difference in median time from antiviral initiation to resolution of hypoxia (59.9 vs. 42.5 h) and to resolution of fever (21.6 vs. 26.6 h). There were no differences in secondary outcomes. Conclusion: Baloxavir was not associated with longer time to resolution of hypoxia or fever in comparison to oseltamivir. Results must be taken in context of variations in seasonal influenza subtype and resistance rates.

Histoplasmosis in Solid Organ Transplantation - Barros, Nicolas; Wheat, L. Joseph (Journal of Fungi, 2024)
Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global distribution with shifting epidemiology during recent decades. While in immunocompetent individuals infection is usually self-resolving, solid organ transplant recipients are at increased risk of symptomatic disease with dissemination to extrapulmonary tissue. Diagnosis of histoplasmosis relies on direct observation of the pathogen (histopathology, cytopathology, and culture) or detection of antigens, antibodies, or nucleic acids. All transplant recipients with histoplasmosis warrant therapy, though the agent of choice and duration of therapy depends on the severity of disease. In the present article, we describe the pathogenesis, epidemiology, clinical manifestations and management of histoplasmosis in solid organ transplant recipients.

Nontuberculous Mycobacterial Infections in Pediatric Solid Organ Transplant and Hematopoietic Cell Transplant Recipients - Albert, Jonathan; Daley, Charles L; Lin, Philana Ling (Journal of the Pediatric Infectious Diseases Society, 2024)
The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug–drug interactions.

Oral β-Lactams, Fluoroquinolones, or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Uncomplicated Escherichia coli or Klebsiella Species Bacteremia From a Urinary Tract Source - Alzaidi, Sameer; Veillette, John J; May, Stephanie S; Olson, Jared; Jackson, Katarina; Waters, C Dustin; Butler, Allison M; Hutton, Mary A; Buckel, Whitney R; Webb, Brandon J (Open Forum Infectious Diseases, 2024)
Fluoroquinolones (FQs) are effective for oral step-down therapy for gram-negative bloodstream infections but are associated with unfavorable toxic effects. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability β-lactams (HBBLs).In this multicenter observational cohort study, we simulated a 3-arm registry trial using causal inference methods to compare the effectiveness of FQs, TMP-SMX, or HBBLs for gram-negative bloodstream infections oral step-down therapy. The study included adults treated between January 2016 and December 2022 for uncomplicated Escherichia coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤4 days of effective intravenous antibiotics. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting.Of 2571 patients screened, 648 (25%) were included. Their median age (interquartile range) was 67 (45–78) years, and only 103 (16%) were male. Characteristics were well balanced between groups. Compared with FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, 0.91 [95% confidence interval, .30–2.78]), and HBBLs had a higher risk of recurrence (2.19 [.95–5.01]), although this difference was not statistically significant. Most HBBLs (70%) were not optimally dosed for bacteremia. A total antibiotic duration ≤8 days was associated with a higher recurrence rate in select patients with risk factors for failure.FQs and TMP-SMX had similar effectiveness in this real-world data set. HBBLs were associated with higher recurrence rates but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.

Impact of Respiratory Viral Infections in Transplant Recipients - Bahakel, Hannah; Waghmare, Alpana; Madan, Rebecca Pellet (Journal of the Pediatric Infectious Diseases Society, 2024)
Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed bacterial and fungal pneumonia, chronic graft dysfunction, and graft failure as a result of RVIs. Recent multicenter retrospective studies and prospective studies utilizing contemporary molecular diagnostic techniques have better delineated the epidemiology and outcomes of RVIs in pediatric transplant recipients and have advanced the development of preventative vaccines and treatment interventions in this population. In this review, we will define the epidemiology and outcomes of RVIs in SOT and HSCT recipients, describe the available assays for diagnosing a suspected RVI, highlight evolving management and vaccination strategies, review the risk of donor derived RVI in SOT recipients, and discuss considerations for delaying transplantation in the presence of an RVI.

Virus-Specific T Cells for the Treatment of Systemic Infections Following Allogeneic Hematopoietic Cell and Solid Organ Transplantation - Green, Abby; Rubinstein, Jeremy D; Grimley, Michael; Pfeiffer, Thomas (Journal of the Pediatric Infectious Diseases Society, 2024)
Viral infections are a major source of morbidity and mortality in the context of immune deficiency and immunosuppression following allogeneic hematopoietic cell (allo-HCT) and solid organ transplantation (SOT). The pharmacological treatment of viral infections is challenging and often complicated by limited efficacy, the development of resistance, and intolerable side effects. A promising strategy to rapidly restore antiviral immunity is the adoptive transfer of virus-specific T cells (VST). This therapy involves the isolation and ex vivo expansion or direct selection of antigen-specific T cells from healthy seropositive donors, followed by infusion into the patient. This article provides a practical guide to VST therapy by reviewing manufacturing techniques, donor selection, and treatment indications. The safety and efficacy data of VSTs gathered in clinical trials over nearly 30 years is summarized. Current challenges and limitations are discussed, as well as opportunities for further research and development.

Pre-Transplantation Strategies for Infectious Disease Mitigation and Prevention - Heald-Sargent, Taylor; Michaels, Marian G; Ardura, Monica I (Journal of the Pediatric Infectious Diseases Society, 2024)
Pediatric Infectious Disease (ID) clinicians play a critical role in helping prevent and mitigate infectious risks in children peri- and post-transplantation. Prevention starts during the pre-transplant evaluation and persists throughout the solid organ transplant and hematopoietic cell transplant continuum. The pre-transplant evaluation is an opportunity to screen for latent infections, plan preventative strategies, optimize immunizations, and discuss risk mitigation practices. An ideal pre-transplant evaluation establishes a relationship with the family that further promotes post-transplant infectious risk reduction. This manuscript builds on shared pediatric ID prevention strategies, introduces updated ID testing recommendations for transplant donors/candidates, highlights emerging data, and identifies ongoing knowledge gaps that are potential areas of research.

Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective - Hsu, Alice Jenh; Hanisch, Benjamin R; Fisher, Brian T; Huppler, Anna R (Journal of the Pediatric Infectious Diseases Society, 2024)
Invasive fungal disease (IFD) remains a significant cause of morbidity and mortality in children undergoing transplantation. There is a growing armamentarium of novel antifungal agents recently approved for use or in late stages of clinical development. The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed.

Adjunct Terbinafine in Patients With Leukemia and Invasive Fusariosis With Skin Lesions: Discordance Between Responses of Skin Lesions and Systemic Outcomes - Matsuo, Takahiro; Wurster, Sebastian; Jiang, Ying; Tarrand, Jeffrey; Kontoyiannis, Dimitrios P (Open Forum Infectious Diseases, 2024)
To theEditor—Invasive fusariosis (IF) is a severe opportunistic mold infection that often results in poor outcomes, especially for patients with hematological malignancies [1–4]. Skin involvement is the second most common manifestation of IF after pulmonary involvement [1–3]. While in vitro studies showed synergistic effects of the squalene epoxidase inhibitor terbinafine (TRB) when combined with triazoles [5] or liposomal amphotericin B (L-Amb) [6] against various fungal pathogens, including Fusarium species, clinical data to support these findings are limited. As TRB has poor penetration in lungs and other visceral tissues, in contrast to its excellent concentration in skin [7], we hypothesized that there might be discordance between good responses of Fusarium skin lesions to TRB but poor systemic outcomes in IF patients treated with adjunct TRB (aTRB). Therefore, we retrospectively reviewed adult leukemia patients (aged ≥18 years) with culture-documented IF at MD Anderson Cancer Center (Houston, Texas) from 2009 to 2021. Among 140 IF patients (114 proven, 26 probable, European Organization for Research and Treatment of Cancer Mycoses Study Group definitions) [8], 71 patients (51%) had skin involvement. Of those, we identified 14 patients who received oral aTRB (dose range, 250–1000 mg/day; duration, 3–128 days) (Table 1). Their median age was 46 years (range, 21–80 years); 13 (93%) were male. Ten patients (71%) had acute myeloid leukemia/myelodysplastic syndrome. All patients had neutropenia (<500/µL) and 4 (29%) had undergone prior allogenic hematopoietic stem cell transplantation. The majority (13 patients [93%]) had disseminated skin lesions. In addition to aTRB, 13 patients received voriconazole + L-Amb and 1 received posaconazole + L-Amb. The median time from IF diagnosis to aTRB initiation was 8 days (range, 0–74 days). While skin lesions on day 42 after aTRB initiation or at the time of earlier death were improved (5 patients [36%]) or stabilized (4 patients [29%]) in 64% of patients, 10 of 14 (71%) had progression of IF in sites with poor pharmacologic exposures of aTRB (lungs in 7 patients, sinus in 2 patients, endophthalmitis in 1 patient). Notably, 71% of patients died within 42 days of aTRB initiation.

Cryptococcus neoformans Infections Differ Among Human Immunodeficiency Virus (HIV)–Seropositive and HIV-Seronegative Individuals: Results From a Nationwide Surveillance Program in France - Paccoud, Olivier; Desnos-Ollivier, Marie; Cassaing, Sophie; Boukris-Sitbon, Karine; Alanio, Alexandre; Bellanger, Anne-Pauline; Bonnal, Christine; Bonhomme, Julie; Botterel, Françoise; Bougnoux, Marie-Elisabeth; Brun, Sophie; Chouaki, Taieb; et al. (Open Forum Infectious Diseases, 2024)
Abstract Among 1107 cryptococcosis cases from the French surveillance network (2005–2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus.

Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial - Russo, Domenico; Schmitt, Michael; Pilorge, Sylvain; Stelljes, Matthias; Kawakita, Toshiro; Teal, Valerie L.; Haber, Barbara; Bopp, Charlene; Dadwal, Sanjeet S.; Badshah, Cyrus (The Lancet Haematology, 2024)

Current and Emerging Antiviral Agents in the Prevention and Treatment of Cytomegalovirus in Pediatric Transplant Recipients - Valencia Deray, Kristen G; Danziger-Isakov, Lara A; Downes, Kevin J (Journal of the Pediatric Infectious Diseases Society, 2024)
Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients ≥12 years of age, though it has no current role in CMV prevention. More research is needed to fully elucidate the roles, efficacy, and safety of these newer agents in prevention and treatment of CMV in pediatric transplant recipients.

A Focused Review of Epstein-Barr Virus Infections and PTLD in Pediatric Transplant Recipients: Guidance From the IPTA and ECIL Guidelines - Yamada, Masaki; L'Huillier, Arnaud G; Green, Michael (Journal of the Pediatric Infectious Diseases Society, 2024)
Epstein-Barr Virus (EBV) diseases, including EBV-associated post-transplant lymphoproliferative disorder (PTLD) remain important causes of morbidity and mortality in children undergoing solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Despite progress in the prevention of EBV disease including PTLD (EBV/PTLD) in HCT, key questions in the prevention, and management of these infectious complications remain unanswered. The goal of this manuscript is to highlight key points and recommendations derived from the consensus guidelines published by the International Pediatric Transplant Association and the European Conference on Infections in Leukemia for children undergoing SOT and HCT, respectively. Additionally, we provide background and guidance on the use of EBV viral load measurement in the prevention and management of these children.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: I-Methodology for the development of consensus practice guidelines - Wilkinson, James D.; Allen, Upton; Green, Michael; Dipchand, Anne I.; Dharnidharka, Vikas R.; Esquivel, Carlos O.; Maecker-Kolhoff, Britta; Preiksaitis, Jutta; Swerdlow, Steven H.; Webber, Steven A.; IPTA Pediatric PTLD Consensus Guidelines Conference (Pediatric Transplantation, 2024)
The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities. The results of each working group (Definitions, Prevention, Management, and Epstein-Barr viral [EBV] load/Biomarker Monitoring) are presented in separate manuscripts within this volume of Pediatric Transplantation.
Keywords: Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders; Organ Transplantation; PTLD; Postoperative Complications; Viral Load; children; pediatric transplantation; pediatrics; post-transplant lymphoproliferative; practice guidelines

Epidemiology, clinical manifestations, and outcome of mucormycosis in solid organ transplant recipients: a systematic review of reported cases - Palomba, Emanuele; Colaneri, Marta; Azzarà, Cecilia; Fava, Marco; Maccaro, Angelo; Renisi, Giulia; Viero, Giulia; Kaur, Harsimran; Chakrabarti, Arunaloke; Gori, Andrea; Lombardi, Andrea; Bandera, Alessandra (Open Forum Infectious Diseases, 2024)
Mucormycosis is an emerging disease primarily affecting the immunocompromised host, but scarce evidence is available for solid organ transplant recipients (SOTR). We systematically reviewed 183 cases occurring in SOTR, exploring epidemiology, clinical characteristics, causative pathogens, therapeutic approaches, and outcomes. Kidney transplants accounted for half of the cases, followed by heart (18.6%), liver (16.9%) and lung (10.4%). Diagnosis showed a dichotomous distribution, with 63.7% of cases reported within 100 days of transplantation and 20.6% occurring at least one year after transplant. The 90-day and 1-year mortality rates were 36.3% and 63.4%, respectively. Disseminated disease had the highest mortality at both time points (75% and 93%). Treatment with more than three immunosuppressive drugs showed a significant impact on 90-day mortality (OR 2.33, 95%CI 1.02-5.66; p=0.0493), as did a disseminated disease manifestation (OR 8.23, 95%, CI 2.20-36.71; p=0.0027) and the presence of diabetes (OR 2.35, 95%, CI 1.01-5.65; p=0.0497). Notably, prophylaxis was administered to twelve cases with amphotericin B. Further investigations are needed to validate these findings and to evaluate the potential implementation of prophylactic regimens in high-risk SOTR.

CDC test - Chagas Disease Molecular Detection CDC-10475 (2024)

CDC test - Chagas Disease Serology CDC-10458 (2024)

SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency - Li, Yijia; Choudhary, Manish C.; Regan, James; Boucau, Julie; Nathan, Anusha; Speidel, Tessa; Liew, May Yee; Edelstein, Gregory E.; Kawano, Yumeko; Uddin, Rockib; Deo, Rinki; Marino, Caitlin; et al. (Science Translational Medicine, 2024)
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups ( P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2–specific humoral responses, whereas only the S-HT group had reduced T cell–mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection. , SARS-CoV-2 clearance differs by the extent of immunosuppression, with prolonged viral shedding occurring in those with severe immunosuppression. , Editor’s summary Interrogating Infection in Immunosuppression. Individuals who are immunosuppressed remain at increased risk of severe COVID-19, but this heterogenous patient pool should not be considered a monolith. Here, Li et al. asked whether the extent of immunosuppression a person has influences their ability to develop immunity and clear SARS-CoV-2 infections. The authors found that severe immunosuppression due to hematologic malignancy or transplant resulted in the longest time to viral clearance. These individuals also had evidence of increased intrahost viral evolution associated with resistance to antibody therapy and were marked by impaired humoral and T cell responses. Individuals with severe immunosuppression due to autoimmunity or B cell deficiency had, expectedly, impaired humoral responses but intact T cell responses, and those with nonsevere immunodeficiency had intact SARS-CoV-2–specific immunity mostly comparable to control participants. Together, these results highlight the importance of considering the type and severity of immunosuppression an individual is experiencing when considering their antiviral immunity. —Courtney Malo

Clinical Characteristics and Outcomes of Endemic Mycoses after Solid Organ Transplantation: A Comprehensive Review - Abad, Cybele Lara R; Razonable, Raymund R (Open Forum Infectious Diseases, 2024)
Abstract Background Geographically endemic fungi can cause significant disease among solid organ transplant (SOT) recipients. We provide an update on the epidemiology, clinical presentation and outcomes of 5 endemic mycoses in SOT recipients. Methods Multiple databases were reviewed from inception through May 2023 using key words for endemic fungi (e.g. Coccidioidomycosis or Coccidioides, Histoplasmosis or histoplasma, etc.). We included adult SOT recipients and publications in English or with English translation. Results Among 16 cohort studies that reported on blastomycosis (n=3), coccidioidomycosis (n=5), histoplasmosis (n=4), and various endemic mycoses (n=4), the incidence rates varied: coccidioidomycosis (1.2-5.8%); blastomycosis (0.14-0.99%) and histoplasmosis (0.4-1.1%). There were 204 reports that described 268 unique cases of endemic mycoses, including 172 histoplasmosis, 31 blastomycosis, 34 coccidioidomycosis, 6 paracoccidioidomycosis, and 25 talaromycosis. The majority of patients were male (176/261, 67.4%). Transplanted allografts were mostly kidney (191/268, 71.3%), followed by liver (n=39, 14.6%), heart (n=18, 6.7%), lung (n=13, 4.9%), combined kidney-liver, and kidney-pancreas (n=6, 2.7%). In all five endemic mycoses, most patients presented with fever (162/232, 69.8%) and disseminated disease (179/268, 66.8%). Cytopenias were frequently reported for histoplasmosis (71/91, 78.0%), coccidioidomycosis (8/11, 72.7%) and talaromycosis (7/8, 87.5%). Graft loss was reported in 12/136 patients (8.8%). All-cause mortality was reported in 71/267 (26.6%); half (n=34, 50%) of the deaths were related to the underlying mycoses. Conclusions Endemic mycoses commonly present with fever, cytopenias and disseminated disease in SOT recipients. There is a relatively high rate of all-cause mortality, including many that were attributed to endemic mycoses.

Overcoming barriers and stigma: new frontiers in solid organ transplantation for people with HIV - Storm, K.; Durand, C. M. (Clinical Microbiology Reviews, 2024)
SUMMARY There is a growing need for solid organ transplantation (SOT) for people living with human immunodeficiency virus (HIV). With the advent of antiretroviral therapy, people living with HIV are experiencing increased life expectancies and are, therefore, developing more comorbidities, including end-stage organ disease. In cases of advanced organ failure, SOT is often the best therapeutic option to improve quality of life and overall survival. As organ shortages persist, transplantation of organs from donors with HIV to recipients with HIV has become a potential therapeutic option. This article first reviews the current state of organ transplantation from donors without HIV to recipients with HIV (HIV D−/R+) by organ and discusses key lessons learned from these transplant trials, including those about drug-drug interactions, rejection, and opportunistic infections. It then explores transplantation from donors with HIV to recipients with HIV (HIV D+/R+), a new frontier. Finally, it investigates challenges of implementation, including public awareness and regulatory requirements, and explores future directions for SOT in people living with HIV.

Individualized Antibiotic Plans as a Quality Improvement Initiative to Reduce Carbapenem Use for Hematopoietic Cell Transplant Patients at a Freestanding Pediatric Hospital - Brothers, Adam W; Pak, Daniel J; Poole, Nicole M; Kronman, Matthew P; Bettinger, Brendan; Wilkes, Jennifer J; Carpenter, Paul A; Englund, Janet A; Weissman, Scott J (Clinical Infectious Diseases, 2024)
Providers must balance effective empiric therapy against toxicity risks and collateral damage when selecting antibiotic therapy for patients receiving hematopoietic cell transplant (HCT). Antimicrobial stewardship interventions during HCT are often challenging due to concern for undertreating potential infections.In an effort to decrease unnecessary carbapenem exposure for patients undergoing HCT at our pediatric center, we implemented individualized antibiotic plans (IAPs) to provide recommendations for preengraftment neutropenia prophylaxis, empiric treatment of febrile neutropenia, and empiric treatment for hemodynamic instability. We compared monthly antibiotic days of therapy (DOT) adjusted per 1000 patient-days for carbapenems, antipseudomonal cephalosporins, and all antibiotics during two 3-year periods immediately before and after the implementation of IAPs to measure the impact of IAP on prescribing behavior. Bloodstream infection (BSIs) and Clostridioides difficile (CD) positivity test rates were also compared between cohorts. Last, providers were surveyed to assess their experience of using IAPs in antibiotic decision making.Overall antibiotic use decreased after the implementation of IAPs (monthly reduction of 19.6 DOT/1000 patient-days; P = .004), with carbapenems showing a continuing decline after IAP implementation. BSI and CD positivity rates were unchanged. More than 90% of providers found IAPs to be either extremely or very valuable for their practice.Implementation of IAPs in this high-risk HCT population led to reduction in overall antibiotic use without increase in rate of BSI or CD test positivity. The program was well received by providers.

Oral Antibiotics for Treatment of Gram-Negative Bacteremia in Solid Organ Transplant Recipients: A Propensity Score Weighted Retrospective Observational Study - Nussbaum, Eliezer Zachary; Koo, Sophia; Kotton, Camille N (Clinical Infectious Diseases, 2024)
Background. We assessed the safety and efficacy of oral antibiotic step-down therapy for uncomplicated gram-negative blood stream infections in solid-organ transplant recipients. Methods. We identified all solid-organ transplant recipients within the Massachusetts General and Brigham and Women’s Hospital systems from 2016 to 2021 with uncomplicated gram-negative bacteremia involving an organism susceptible to an acceptably bioavailable oral antibiotic agent. Using inverse probability of treatment-weighted models based on propensity scores adjusting for potential clinical confounders, we compared outcomes of those transitioned to oral antibiotics with those who continued intravenous (IV) therapy for the duration of treatment. Primary endpoints were mortality, bacteremia recurrence, and reinitiation of IV antibiotics. Secondary endpoints included length of stay, Clostridioides difficile infection, treatmentassociated complications, and tunneled central venous catheter placement. Results. A total of 120 bacteremia events from 107 patients met inclusion criteria in the oral group and 42 events from 40 patients in the IV group. There were no significant differences in mortality, bacteremia recurrence, or reinitiation of IV antibiotics between groups. Patients transitioned to oral antibiotics had an average length of stay that was 1.97 days shorter (95% confidence interval [CI], −.39 to 3.56 days; P = .005). Odds of developing C. difficile and other treatment-associated complications were 8.4 times higher (95% CI, 1.5–46.6; P = .015) and 6.4 times higher (95% CI, 1.9–20.9; P = .002), respectively, in the IV group. Fifty-five percent of patients in the IV group required tunneled catheter placement. There was no difference in treatment duration between groups. Conclusions. Oral step-down therapy was effective and associated with fewer treatment-related adverse events.

Trends in the activity of mold-active azole agents against Aspergillus fumigatus clinical isolates with and without cyp51 alterations from Europe and North America (2017–2021) - Pfaller, M. A.; Carvalhaes, C. G.; Rhomberg, P. R.; Desphande, L. M.; Castanheira, M. (Journal of Clinical Microbiology, 2024)

Donor-derived endemic mycoses after solid organ transplantation: A review of reported cases - Abad, Cybele Lara R.; Razonable, Raymund R. (Clinical Transplantation, 2024)
Background Donor-derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians. Methods Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor-derived infections (DDI) were included. Results Twenty-four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor-derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2–35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4–48) months after transplantation. The single reported possible donor-derived talaromycosis occurred in a man whose organ donor had at-risk travel to Southeast Asia. Collectively, the majority of donors had high-risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor-derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%). Conclusion Donor-derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.
Keywords: coccidioides; endemic fungi; histoplasma; talaromyces; transplantation

Kidney Transplantation - Abramyan, Shogik; Hanlon, Matthew (StatPearls, 2024)
Kidney transplantation is often the preferred treatment for those with end-stage renal disease. The discipline of kidney transplantation has grown tremendously over the past 50 years.  Patients with end-stage renal disease have better long-term survival if they are placed on the waiting list and eventually undergo kidney transplantation than those who stay on dialysis. Furthermore, those who undergo transplantation often experience a better quality of life and a projected survival benefit of 10 years over those who remain on dialysis. Since kidney transplantation was first successfully performed by Dr. Joseph Murray in 1954, there have been major developments in transplantation and immunology, allowing for a wider selection of acceptable donors and recipients.

Heart Transplantation - Ahmed, Talha; Jain, Ankit (StatPearls, 2024)
Patients with advanced heart failure requiring mechanical circulatory support and inotropic support have a poor prognosis. Cardiac transplantation in a selected cohort of such patients can be the treatment of choice. The early experience with heart transplants was disappointing. In 1967, the first patient to receive a heart transplant died of an overwhelming infection after 17 days. However, with the advent of immunosuppressive therapies and a better understanding of human anatomy and surgical techniques, cardiac transplantation started gaining popularity in the 1990s. The International Society for Heart and Lung Transplantation (ISHLT) reported maximum transplants during the period of 1993-2004; however, in recent years, the numbers reported have grown even further. With well-defined indications now set forth by the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) and European Society of Cardiology (ESC) in collaboration with ISHLT, more people are on the waiting list than is the availability of the organ itself. This review will focus on the updated guidelines on indications and contraindications of a heart transplant, commonly utilized techniques, post-transplant immunosuppression, and common complications of the procedure.

The Next Outbreak Looms on the Horizon: Measles and Potential Impacts on Transplant Recipients - Al Jurdi, Ayman; Kotton, Camille N. (Transplantation, 2024)

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents - Allen, Upton D.; L'Huillier, Arnaud G.; Bollard, Catherine M.; Gross, Thomas G.; Hayashi, Robert J.; Höcker, Britta; Maecker-Kolhoff, Britta; Marks, Stephen D.; Mazariegos, George Vincent; Smets, Francoise; Trappe, Ralf U.; Visner, Gary; et al. (Pediatric Transplantation, 2024)
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.
Keywords: Epstein–Barr virus; PTLD; child; management; solid organ transplantation

Infections in Heart and Lung Transplant Recipients - Alsaeed, Mohammed; Husain, Shahid (Infectious Disease Clinics of North America, 2024)

The International Society for Heart and Lung Transplantation (ISHLT): 2024 infection definitions for durable and acute mechanical circulatory support devices - Aslam, Saima; Cowger, Jennifer; Shah, Palak; Stosor, Valentina; Copeland, Hannah; Reed, Anna; Morales, David; Giblin, Gerard; Mathew, Jacob; Morrissey, Orla; Morejon, Paola; Nicoara, Alina; et al. (The Journal of Heart and Lung Transplantation, 2024)

The impact of induction therapy on the risk of posttransplant lymphoproliferative disorder in adult kidney transplant recipients with donor-recipient serological Epstein-Barr virus mismatch - Attieh, Rose Mary; Wadei, Hani M.; Mao, Michael A.; Mao, Shennen A.; Pungpapong, Surakit; Taner, C. Burcin; Jarmi, Tambi; Cheungpasitporn, Wisit; Leeaphorn, Napat (American Journal of Transplantation, 2024)

Bacterial Infections - Averbuch, Dina (The EBMT Handbook, 2024)
Abstract HCT patients are at risk for severe bacterial infection, the most frequent of them are bloodstream infections (BSI). The majority occur at the pre-engraftment period. Primary BSIs are mainly central line catheter-related (CRBSI) or mucosal barrier injury-associated. Secondary BSI accompanies site-specific infection (e.g., Pseudomonas aeruginosa pneumonia and BSI). GNB has become an increasingly common cause of BSI, and are associated with high mortality. Specifically, an increase in infections due to resistant GNB, such as ESBL Enterobacterales, carbapenemase-producing Enterobacterales (CPE), MDR GNB, or difficult-to-treat (DTR) Pseudomonas aeruginosa, leads to delay in appropriate therapy and increases mortality. Empirical antibiotic therapy should be started immediately when bacterial infection is suspected. It should be based on escalation/de-escalation principles reflecting the patient’s clinical condition, prior colonization or infection with resistant bacteria, and local epidemiology. Main targeted therapy options for severe infections caused by resistant GNB include: carbapenems for ESBL Enterobacterales; meropenem-vaborbactam or ceftazidime-avibactam for KPC-producing Enterobacterales; ceftazidime-avibactam for OXA-48-like-producing Enterobacterales; aztreonam plus ceftazidime–avibactam, or cefiderocol for Metallo-β-lactamases-producing Enterobacterales; ceftolozane-tazobactam for DTR Pseudomonas aeruginosa . Routine combination therapy of β-lactams with aminoglycosides/fluoroquinolone (FQ)/polymyxins for infection due to MDR GNB susceptible to β-lactam is not recommended (with a possible exception of a severe infections due to Pseudomonas aeruginosa in neutropenic patients). High-dose prolonged β-lactam infusion can maximize efficacy. Source control with CVC removal is important. Antibiotic treatment should be continued for at least 7 days until the infection is microbiologically eradicated and all clinical signs resolved, with the patient afebrile for at least 4 days. Antimicrobial stewardship aims to individualize an empirical approach to patients with suspected infection, limiting unnecessary antibiotic use, and optimizing treatment based on pharmacokinetic/pharmacodynamic principles. Infection control is crucial to limit the spread of MDR pathogens. Fluoroquinolone prophylaxis is controversial. Encapsulated bacteria ( Streptococcus pneumoniae and Haemophilus influenzae ) cause infection during the late post-engraftment period. Preventive measures include oral prophylaxis, IVIg, and vaccinations.

Pancreas Transplantation - Bahar, Syeda Gul; Devulapally, Pavan (StatPearls, 2024)
The first fruitful pancreatic transplant was carried out by WD Kelly in the year 1966. The results of pancreas transplantation have greatly improved as compared to the first one done in 1966, due to technical improvements and better immunosuppressive therapy over the last three decades. Transplantation of the pancreas is the only near cure treatment for type 1 diabetic patients. After the making of the International Pancreas Transplant Registry in 1984, data on more than 48000 pancreas transplants have been collected in the subsequent 30 years. Diabetes mellitus is the leading cause of end-stage renal disease worldwide.  Kidney transplantation is the treatment of choice for end-stage renal disease, but in diabetic patients, the metabolic disturbances persist and may get worse even when the kidney alone is transplanted. The only treatment that maintains normal glucose levels and normalizes serum levels of glycosylated hemoglobin in type 1 diabetes patients is the pancreas transplantation. 1 yr and 5 yr results of simultaneous kidney and pancreas transplantation are comparable to the kidney, liver, and heart transplantation.

Clinically Relevant Drug Interactions in HCT - Bauters, Tiene; Dadkhah, Adrin (The EBMT Handbook, 2024)
Abstract Patients undergoing HCT receive polymedication which carries the potential to result in drug interactions. To avoid unexpected outcomes, attention to drug interactions is crucial, especially when drugs with a narrow therapeutic index or inherent toxicity profile are involved.

Maribavir for refractory cytomegalovirus infection (with or without resistance) in solid organ transplant recipients: subgroup analysis of the phase 3 randomized SOLSTICE study - Blumberg, Emily A.; Witzke, Oliver; Mbbs, Mark Harber; Ison, Michael G.; Saliba, Faouzi; Kamar, Nassim; Sundberg, Aimee K.; Gu, Joan; Kumar, Deepali; La Hoz, Ricardo M. (The Journal of Heart and Lung Transplantation, 2024)

Haemorrhagic Cystitis and Renal Dysfunction - Cesaro, Simone (The EBMT Handbook, 2024)
Abstract Haemorrhagic cystitis is a frequent complication after haematopoietic cell transplantation. Supportive measures (analgesics, antispasmodics, blood product transfusions and hyperhydration) are the main mode of treatment, with or without antivirals or experimental approaches (hyperbaric oxygen therapy, fibrin-glue or platelet-rich plasma application, adoptive immunotherapy).

Expanding Access to Organ Transplant for People Living With HIV: Can Policy Catch Up to Outcomes Data? - Chandran, Sindhu; Stock, Peter G.; Roll, Garrett R. (Transplantation, 2024)
Advances in antiretroviral and immunosuppressive regimens have improved outcomes following solid organ transplantation in people living with HIV (PLWH). The HIV Organ Policy and Equity Act was conceived to reduce the discard of HIV-positive organs and improve access to transplant for PLWH. Nevertheless, PLWH continue to experience disproportionately low rates of transplant. This overview examines the hurdles to transplantation in PLWH with end-organ disease, the potential and realized impact of the HIV Organ Policy and Equity Act, and changes that could permit expanded access to organ transplant in this population.

Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM - Chang, Christina C; Harrison, Thomas S; Bicanic, Tihana A; Chayakulkeeree, Methee; Sorrell, Tania C; Warris, Adilia; Hagen, Ferry; Spec, Andrej; Oladele, Rita; Govender, Nelesh P; Chen, Sharon C; Mody, Christopher H; et al. (The Lancet Infectious Diseases, 2024)

Intestinal and Multivisceral Transplantation - Cheesman, Nicolas D.; Dattilo, Jeffery B. (StatPearls, 2024)
Multivisceral transplantation (MVT) can be categorized into many different organ combinations, but for this review, the focus will be on concurrent transplantation of the intestine, stomach, hepatobiliary system, and the pancreaticoduodenal complex – which can also be performed in a modified fashion by “cherry-picking” different organs that suit the recipient’s condition. Some approach MVT by the replacement of any organ that relies on the superior mesenteric and celiac artery. The concept of a total multi-visceral abdominal transplant was introduced in 1960 by the father of modern transplantation – Thomas Starzl.  Originally performed on dogs to study the effects of mass denervation of homografts, the concept was not abandoned, and in the 80’s it was attempted again, but this time on humans.  Unfortunately, the first patient suffered post-operative hemorrhage; the following two developed posttransplant lymphoproliferative disorder (PTLD) and never left the hospital.  The first hospital discharge MVT was performed in December of 1989. The patient was able to survive 10 months without parenteral support and ultimately passed from metastatic pancreatic cancer.  To date since 1988, there have been 1,916 intestinal transplantations combined with other organs, most commonly liver-intestine-pancreas (1,105) – with the second most common being liver-intestine (464). With advancements in immunosuppression and post-operative care, the 1-year survival rate has increased from approximately 40% to over 80% since the 1990s, with 5-year survival being around 60%.

Risk factors for Pneumocystis jirovecii pneumonia after kidney transplantation: A systematic review and meta‐analysis - Cheng, Bingjie; Qi, Chang; Zhang, Senlin; Wang, Xiaowen (Clinical Transplantation, 2024)
Background and objective: Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients. Methods: We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP. Results: 27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56–6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53–6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70–6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44–5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57–4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37– (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92– (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28–.98; p = .04) were significantly associated with PJP occurrence. Conclusion: Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.

Hepatitis B Vaccine Compliance, Serologic Response, and Durability in Adult Thoracic Organ Transplant Recipients - Chiu, Chia‐Yu; Sampathkumar, Priya; Brumble, Lisa M.; Vikram, Holenarasipur R.; Watt, Kymberly D.; Beam, Elena (Clinical Transplantation, 2024)
Introduction: Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients. Methods: We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav-B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30). Results: Among 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav-B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav-B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav-B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p < 0.001). Conclusions: Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav-B provided a higher vaccine completion rate and seroprotection than the 3-dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

Efficacy of Newer Nucleos(t)ide Analogs After Hepatitis B Immunoglobulin Discontinuation Against Hepatitis B and D Recurrence in Liver Transplant Recipients - Cholongitas, Evangelos; Oikonomou, Theodora; Bafa, Konstantina; Sinakos, Emmanouil; Papatheodoridis, George V.; Goulis, Ioannis (Transplantation, 2024)
Background. The use of nucleos(t)ide analogs (NAs) with a high genetic barrier to resistance, namely entecavir and tenofovir, has improved the efficacy of antiviral prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the optimal duration and dosage of hepatitis B immunoglobulin (HBIG) administration, particularly in patients transplanted for HBV and hepatitis D virus (HDV) coinfection, remains controversial. Methods. We evaluated 28 patients transplanted for HBV/HDV cirrhosis. After LT, each patient received a fixed scheme of low-dose HBIG plus NA for 6 mo post-LT and then continued with long-term NA prophylaxis (entecavir: 8, tenofovir: 20 patients). Results. During 72 mo of follow-up, reappearance of hepatitis B surface antigen at low titers was observed in 1 (3.6%) patient at 33 mo after HBIG discontinuation, which became negative after a single dose of HBIG 1000 IU/L, whereas both serum HBV DNA and HDV RNA remained persistently undetectable and without any clinical or biochemical evidence of HBV/HDV recurrence. Conclusions. We showed for the first time the efficacy of a short, fixed scheme of low-dose HBIG plus NA followed by long-term NA monoprophylaxis against HBV/HDV recurrence after LT, although careful follow-up is needed after HBIG discontinuation, whereas further larger studies are needed to confirm these findings.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients - Cui, Jiaqi; Zhou, Yuhang; Zhao, Kui; Li, Xudong; Zhang, Hanyue; Zhang, Xiangzhong; Sun, Yanling; Long, Bing (Clinical Transplantation, 2024)
Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.
Keywords: CMV reactivation; CMV-IVIg; HSCT

Updates in Mucormycosis - Czech, Mary M.; Cuellar-Rodriguez, Jennifer (Infectious Disease Clinics of North America, 2024)

Liver Transplantation - Dababneh, Yara; Mousa, Omar Y. (StatPearls, 2024)
Cirrhosis and decompensated liver disease were the ninth leading cause of death for males in 2016 in the United States. Liver transplantation (LT) is a lifesaving gift and proven intervention in managing patients with acute and chronic end-stage liver disease. It restores normal health, lifestyle and extends lifespan by 15 years. The advent of liver transplantation came as a safety net to treat various liver diseases when all other medical interventions have failed. According to the Scientific Registry of Transplant Recipients data, overall patient survival is excellent, reaching 90% at 1 year following deceased donor liver transplantation and 77% at 5 years. Since liver transplantation was first attempted in 1963, there have been continuous advances and major improvements in the surgical technique, type of organ donation with the expansion of the organ donation pool, and a major focus on the quality of life of both the recipients and donors. Still, there are important challenges, including the shortage of donor organs, selection of liver transplantation candidates, and organ allocation.

Vaccinations - De La Cámara, Rafael; Meisel, Roland (The EBMT Handbook, 2024)
Abstract Vaccination should be considered a routine practice for all HCT receptors , either autologous or allogeneic, adults or children. It should be implemented in all HCT programs. Adult cover is particularly important as they represent 90% of HCTs.

Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry - Donohue, Jack K.; Chan, Ernest G.; Clifford, Sarah; Ryan, John P.; Furukawa, Masashi; Haidar, Ghady; Bertani, Alessandro; Hage, Chadi A.; Sanchez, Pablo G. (Clinical Transplantation, 2024)
Background: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV−) recipients. Methods: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan–Meier analysis. Results: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV− recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. Conclusions: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV− patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV− recipients.

Risk factors and outcomes of bloodstream infection from a urinary source in kidney transplant recipients - Eichenberger, Emily M.; Donzo, Maja Wichhart; Anderson, Rebecca; Karadkhele, Geeta; Pouch, Stephanie M.; Larsen, Christian P. (Clinical Transplantation, 2024)
Background Bacteriuria is common among kidney transplant recipients (KTR). Risk factors and outcomes associated with bloodstream infection due to a urinary source (BSIU) in KTR are poorly understood. Methods This single center case-control study from 2010 to 2022 compared KTR with BSIU to those with bacteria without bloodstream infection (BU). Multivariable logistic regression identified BSIU risk factors, and Cox models assessed its impact on graft failure. Results Among 3435 patients, who underwent kidney transplantation at Emory Hospital, 757 (22%) developed bacteriuria, among whom 142 (18.8%) were BSIU. Male sex, presence of Escherichia coli, Klebsiella pneumoniae, or Pseudomonas species in urine culture, urethral stricture, neuromuscular bladder disorder, and history of diabetes-induced renal failure were independently associated with increased odds of BSIU (Male sex: aOR 2.29, 95% CI 1.52, 3.47, E. coli: aOR 5.14, 95% CI 3.02, 9.13; K. pneumoniae aOR 3.19, 95% CI 1.65, 6.27, Pseudomonas spp aOR 3.06, 95% CI 1.25, 7.18; urethral stricture: 4.10, 95% CI 1.63, 10.3, neuromuscular bladder disorder aOR 1.98, 95% CI 1.09, 3.53, diabetes: aOR 1.64, 95% CI 1.08, 2.49). BSIU was associated with increased hazard of graft failure (HR 1.52, 95% CI 1.05, 2.20). Conclusion Close monitoring is warranted for male KTR with bacteriuria, those with urine cultures positive for Pseudomonas spp, K. pneumoniae, or E. coli, as well as KTR with a history of diabetes-induced renal failure, urethral stricture, or neuromuscular bladder disorder due to their risk for developing BSIU. Future research should explore strategies to mitigate BSIU risk in these high-risk KTR and reduce the associated risk of long-term graft failure.
Keywords: bacteriuria; bloodstream infection; kidney transplant; urinary source

Infections in Patients with Mechanical Circulatory Support - Eichenberger, Emily M.; Phadke, Varun; Busch, Lindsay M.; Pouch, Stephanie M. (Infectious Disease Clinics of North America, 2024)

Lung Nodules and Masses in non-HIV Immunocompromised Patients: A Clinical-Imaging Algorithmic Approach - Franquet, T.; Raoof, S.; Lee, Ks; Han, J.; Gimenez, A.; Brenes, Jm; Asmar, J.; Domingo, P. (CHEST, 2024)
Pulmonary nodules and masses in immunocompromised patients represent a diagnostic challenge due to overlapping radiological and clinical presentations. By integrating clinical context, immune status, and imaging findings, clinicians can more accurately diagnose and manage these lesions, improving patient outcomes. This review presents an algorithmic approach for differentiating between various causes of pulmonary nodules and masses in non-HIV immunocompromised individuals, providing a valuable tool for clinical practice.

Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infections after Allogeneic Hematopoietic Stem Cell Transplantation - Fu, Rong; Xu, Jun; Fan, Zhiping; Qu, Hong; Jiang, Yirong; Xiong, Wenjie; Huang, Fen; Xuan, Li; Xu, Na; Liu, Hui; Wang, Zhixiang; Sun, Jing; et al. (Transplantation and Cellular Therapy, 2024)
Early and accurate identiﬁcation of pathogens in pulmonary infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critically important. The clinical usefulness of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary infections after allo-HSCT remains under discussion. This multicenter retrospective study was conducted to compare mNGS and conventional microbiological tests (CMTs) in identifying the pathogens of pulmonary infections in allo-HSCT recipients. One hundred forty alloHSCT recipients with suspected pulmonary infections who underwent bronchoscopy were included. mNGS and CMTs performed on bronchoalveolar lavage ﬂuid specimens showed 71.4% positivity on mNGS compared to 55.0% positivity on CMTs. mNGS identiﬁed 182 pathogens, including bacteria (n = 88), fungi (n = 35) and viruses (n = 59), compared to 106 pathogens detected by CMTs (bacteria, n = 31; fungi, n = 24; viruses, n = 51). Pulmonary infection was ﬁnally diagnosed in 98 patients, including 22 bacterial, 7 fungal, 18 viral, and 48 mixed infections and 3 infections with an unknown pathogen. Mixed infections were identiﬁed in 50.5% of the patients with pulmonary infection. The sensitivity of mNGS and CMTs for diagnosing pulmonary infections was 88.8% and 69.4%, respectively (P = .001), and the speciﬁcity were 81.0% and 85.7%, respectively (P = .688). Our ﬁndings suggest that mNGS may be a promising technology for diagnosing pulmonary infections in allo-HSCT recipients.

Endemic viral infections in immunocompromised hosts: Dengue, Chikungunya, Zika - Garnica, Marcia; Ramos, Jessica Fernandes; Machado, Clarisse Martins (Current Opinion in Infectious Diseases, 2024)
Educational and preventive measures are the best strategy: vector control, knowledge of the vector’s habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.

The IPTA Nashville consensus conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: II—consensus guidelines for prevention - Green, Michael; Squires, James E.; Chinnock, Richard E.; Comoli, Patrizia; Danziger-Isakov, Lara; Dulek, Daniel E.; Esquivel, Carlos O.; Höcker, Britta; L'Huillier, Arnaud G.; Mazariegos, George Vincent; Visner, Gary A.; Bollard, Catherine M.; et al. (Pediatric Transplantation, 2024)
The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted.

The nuts and bolts of transplant infectious disease training - Harris, Courtney E.; Kumar, Rebecca N.; Haidar, Ghady; La Hoz, Ricardo M.; Gorsline, Chelsea A. (Transplant Infectious Disease, 2024)
The number of transplant infectious disease (TID) fellowship programs has expanded rapidly in the past 5 years, with the creation of many new programs and the expansion of training tracks and dedicated years as the demand for TID physicians grows drastically. This editorial focuses on major factors and complexities that programs should consider in TID fellowship creation, as well as highlighting examples of formative experiences, programmatic structure, and fellow resources that trainees can use to identify their desired career path in TID.

Babesiosis in immunosuppressed hosts: pathogenesis, diagnosis and management - Heller, Howard M. (Current Opinion in Infectious Diseases, 2024)
Babesiosis is likely to become a more frequent infectious complication in immunosuppressed hosts as the areas of endemicity expand. Reduced efficacy of standard therapies is likely to continue emerging so more effort needs to be placed on methods of assessing resistance in vitro and developing more reliable treatments for resistant infections.

Acute Graft-Versus-Host Disease - Holler, Ernst; Greinix, Hildegard; Zeiser, Robert (The EBMT Handbook, 2024)
Abstract Acute graft-versus-host disease (GvHD) remains a major course of short term (100 days and 1 yr) mortality and morbidity after allogeneic stem cell transplantation. The pathophysiology of GvHD is described as a 3 step process starting with initial tissue damage by conditioning followed by host antigen presenting cell activation by damage and pathogen associated molecular patterns and finally resulting in activation of alloreactive T cells and proinflmmatory cytokines inducing target cell apoptosis. This activating cycle elicits multiple regulatory mechanisms and cells such as regulatory T cells and myeloid derived suppressor cells. Besides the disturbed balance between immune activation and immune tolerance, a disturbed capacity of tissue repair contributes to clincal damage.

Cytomegalovirus Post‐Prophylaxis Surveillance in High‐Risk Kidney and Liver Recipients Prevents CMV End‐Organ Disease and Ganciclovir‐Resistance - Jorgenson, Margaret R.; Meyer, Ethan; Leverson, Glen E.; Descourouez, Jillian L.; Saddler, Christopher M.; Smith, Jeannina A.; Rice, John P.; Mandelbrot, Didier A.; Odorico, Jon S. (Clinical Transplantation, 2024)
ABSTRACT Purpose Evaluate cytomegalovirus (CMV) post‐prophylaxis surveillance in high‐risk (D+/R‐) kidney and liver transplant recipients. Methods Adult D+/R‐ patients were included if transplanted between 6/1/15 and 11/30/22 and divided into a pre‐CMV‐stewardship‐era (6/1/15–5/31/18), CMV‐stewardship‐era (6/1/18–6/30/20), and a surveillance‐era (7/1/2020–11/30/2022) then followed through 12 months. The primary objective was to evaluate CMV‐related outcomes. The secondary objective was to assess graft and patient survival by era. Results There were 328 patients in the study period; 133 in the pre‐stewardship‐era, 103 in the stewardship‐era, and 92 in the surveillance‐era. Replication rates in the surveillance‐era were significantly higher, as anticipated due to increased sampling (pre 38.4%, stewardship 33.0%, surveillance 52.2%, p = 0.02). Time from transplant to first replication was similar (pre 214.0 ± 79.0 days, stewardship 231.1 ± 65.5, surveillance 234.9 ± 61.4, p = 0.29). CMV viral load (VL) at first detection, maximum‐VL, and incidence of VL > 100 000 IU/mL were numerically lower in the surveillance era, although not statistically significant. CMV end‐organ disease ( p < 0.0001) and ganciclovir‐resistance ( p = 0.002) were significantly lower in the surveillance era than in both previous eras. Rejection was not different between eras ( p = 0.4). Graft ( p = 0.0007) and patient survival ( p = 0.008) were significantly improved in the surveillance era. Conclusions Post‐prophylaxis surveillance significantly reduced CMV end‐organ disease and resistance. Despite observing increased replication rates in the surveillance era, rejection was not significantly different and there was no graft loss or patient mortality at 12 months.

Hematopoietic Stem Cell Transplantation - Khaddour, Karam; Hana, Caroline K.; Mewawalla, Prerna (StatPearls, 2024)
Hematopoietic stem cell transplant (HPSCT), sometimes referred to as bone marrow transplant, involves administering healthy hematopoietic stem cells to patients with dysfunctional or depleted bone marrow. This procedure has several benefits. It helps to augment bone marrow function. In addition, depending on the disease being treated, it may allow for the destruction of malignant tumor cells. It can also generate functional cells that replace dysfunctional ones in cases like immune deficiency syndromes, hemoglobinopathies, and other diseases. History and Evolution Hematopoietic stem cell transplantation (HPSCT) was first explored for use in humans in the 1950s. It was based on observational studies in mice models, which showed that infusion of healthy bone marrow components into a myelosuppressed bone marrow could induce recovery of its function in the recipient. These animal-based studies soon found their clinical application in humans when the first successful bone marrow transplant was performed between monozygotic twins in New York in 1957 to treat acute leukemia. The performing physician, E. Donnell Thomas, continued his research on the development of bone marrow transplantation and later received the Nobel Prize for Physiology and Medicine for his work. The first successful allogeneic bone marrow transplant was reported in Minnesota in 1968 for a pediatric patient with severe combined immunodeficiency syndrome.  Since then, allogeneic and autologous stem cell transplants have increased in the United States (US) and worldwide. The Center for International Blood and Marrow Transplant Research (CIBMTR) reported over 8000 allogeneic transplants performed in the US in 2016, with an even greater number of autologous transplants; autologous transplants have steadily outpaced allogeneic transplants over time. Definitions Major Histocompatibility Complex (MHC) The human MHC genes on the short arm of chromosome 6 (6p) encode for human leukocyte antigens (HLA) and are highly polymorphic. These polymorphisms lead to significant differences in the resultant expressed human cell-surface proteins. They are divided into MHC class I and MHC class II. Human Leukocyte Antigens (HLA) The HLA proteins are expressed on the cellular surface and play an essential role in alloimmunity. HLA class I molecules, encoded by MHC class I, can be divided into HLA-A, HLA-B, and HLA-C. These proteins are expressed on all cell types and present peptides derived from the cytoplasm and recognized by CD8+ T cells. HLA class II molecules are classified as HLA- DP, HLA-DQ, and HLA-DR, are encoded by MHC class II, can be found on antigen-presenting cells (APCs), and are recognized by CD4+ T cells. Syngeneic Bone Marrow Transplantation The donor and the recipient are identical twins. The advantages of this type of transplant include no risk of graft versus host disease (GVHD) or graft failure. Unfortunately, however, only a very few transplant patients will have an identical twin available for transplantation. Autologous Bone Marrow Transplantation The bone marrow products are collected from the patient and are reinfused after purification methods. The advantage of this type of transplant is no risk of GVHD. The disadvantage is that the reinfused bone marrow products may contain abnormal cells that can cause relapse in the case of malignancy; hence, theoretically, this method cannot be used in all cases of abnormal bone marrow diseases. Allogeneic Transplantation The donor is an HLA-matched family member, an unrelated HLA-matched donor, or a mismatched family donor (haploidentical). Engraftment The process by which infused transplanted hematopoietic stem cells produce mature progeny in the peripheral circulation. Preparative Regimen This regimen comprises high-dose chemotherapy or total body irradiation (TBI) or both, which are administered to the recipient before stem cell infusion to eliminate the largest number of malignant cells and induce immunosuppression in the recipient so that engraftment can occur.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post‐transplant viremia - Khan, Sarah; Mazumder, Ritika; Wang, Xiaofeng; Wang, Yifan; Sims, Omar T; Budev, Marie; Carey, William (Clinical Transplantation, 2024)
Background/aims: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). Methods: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. Results: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). Conclusion: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Pet safety guidelines for pediatric transplant recipients - Kilduff, Stella; Steinman, Benjamin; Xie, Yuping; Kiss-Farengo, Tomas; Foca, Marc; Hayde, Nicole (Pediatric Transplantation, 2024)
Approximately 70% (90.5 million) of United States (US) households own at least one pet. Dogs are the most common, making up about 38% of all household pets, followed by cats, which make up 25%. Other pets such as fish, birds, reptiles, and small animals such as hamsters, gerbils, and rabbits are less common household members. Pets are often considered a part of the family and there are significant medical and psychosocial benefits to pet ownership; however, the possibility of disease transmission exists related to the type of animal and infectious organism, and specific human risk factors. Immunocompromised individuals may be at increased risk of serious illness from zoonotic infections. During the transplant evaluation and routinely posttransplant, the multidisciplinary team should inquire about pet ownership and animal exposures to guide on potential risks. This review discusses the most common diseases seen in various household pets including dogs, cats, birds, fish, and some farm animals. We will also present guidelines for pet safety and include strategies to decrease the risk of infection while supporting the benefits of pet ownership after transplant.
Keywords: infectious risk; transplant

Lung Transplantation - Kumar, Akshay; Anjum, Fatima (StatPearls, 2024)
Lung transplantation is a well-established life-saving treatment to improve the quality of life of patients with end-stage respiratory failure not responding to other medical or surgical interventions. The 36th adult lung and heart-lung transplant report summarize data from 69,200 adult lung transplants that have been performed through June 30, 2018, and reported to the International Thoracic Organ Transplant Registry. The US Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR) reported survival rates of 85% at 1 year, 68% at 3 years, and 55% at 5 years.  Because lung transplantation is evolving both in the application and in success, it is worthwhile to be acquainted with the procedure. The first lung transplant procedure was performed by Dr. James Hardy and colleagues at the University of Mississippi in 1963. The recipient had chronic obstructive pulmonary disease (COPD) but was a suboptimal candidate for several reasons, including the presence of advanced lung cancer and renal insufficiency. While the first successful combined heart and lung transplant was performed in 1981. Since then the field of lung transplantation has advanced in the selection of candidates, operative techniques, critical care management, immunosuppression, and long-term follow-up.

Lung and sinus fungal infection imaging in immunocompromised patients - Lamoth, Frederic; Prakash, Katya; Beigelman-Aubry, Catherine; Baddley, John W. (Clinical Microbiology and Infection, 2024)

Viral Infections - Ljungman, Per; Piñana, Jose Luis; Cesaro, Simone; De La Cámara, Rafael (The EBMT Handbook, 2024)
Abstract Viral infections are important and possibly serious complications to cellular therapies especially allogeneic hematopoietic stem cell transplantation. The most important virus infections are caused by the herpesviruses, adenovirus, and community acquired respiratory viruses including SARS-CoV-2, but also other more rare infections require attention. This chapter discusses some of these infections and their management

Invasive Fungal Diseases - Maertens, Johan A. (The EBMT Handbook, 2024)
Abstract Invasive fungal diseases are potentially life-threatening infectious complications following HCT and CAR-T cell treatment. The successful introduction of azole-based antifungal prophylaxis has dramatically changed the fungal epidemiology and resistance patterns in many institutions. Timely and accurate diagnosis remains a challenge, especially for mould infections, and relies nowadays heavily on the detection of fungal biomarkers, fungal DNA, and sensitive imaging. Various antifungal strategies are in place, and recommendations regarding drugs of choice are available.

Opportunistic Infections Post-Lung Transplantation: Viral, Fungal, and Mycobacterial - Magda, Gabriela (Infectious Disease Clinics of North America, 2024)

Other Life-Threatening Infections - Martino, Rodrigo (The EBMT Handbook, 2024)
Abstract Toxoplasma gondii is a protozoan that commonly infects animals and birds. Primary T. gondii infection in humans and other mammals is usually asymptomatic but leads to lifelong latent infection. Transmission to humans occurs by ingesting tissue cysts from undercooked meat or oocysts (released in the feces of cats). Latent cysts can give rise during immunosuppression to a severe localized reactivation producing, for example, toxoplasma encephalitis or chorioretinitis, with dissemination being common (Martino, et al.Clin Infect Dis 2000;31:1188–95; Martino et al. Clin Infect Dis 2005;40:67–78; Tomblyn et al., Biol Blood Marrow Transplant 2009;15:1143–23; Martino, et al., Clin Infect Dis 1996;23:419–20.). Very detailed guidelines for the management and diagnosis of toxoplasmosis following HCT have been recently finalized for the European Conference of Infections in Leukemia 9th Meeting (ECIL-9) conference and are being considered for publication as of June 2023 (Aerts et al., Under peer-review, 2023).

Diagnosing and Managing Urinary Tract Infections in Kidney Transplant Recipients - McAteer, John; Tamma, Pranita D. (Infectious Disease Clinics of North America, 2024)

Infection Control and Isolation Procedures - Mikulska, Malgorzata (The EBMT Handbook, 2024)
Abstract Infection control is defined as a set of measures aimed at preventing or stopping the spread of infections in healthcare settings. Isolation procedures are a set of standard recommendations designed to reduce the risk of transmission of different infectious agents from body fluids or environmental surfaces.

Neutropenic Fever - Mikulska, Malgorzata (The EBMT Handbook, 2024)
Abstract Fever during neutropenia is almost universal after an HCT. In neutropenic HCT recipients, clinicians are faced with a unique combination of issues: (1) high incidence of bacterial bloodstream infections, (2) high mortality in case of infections due to Gram-negative bacteria unless effective antibiotic treatment is provided promptly, and (3) numerous causes of fever other than bacterial infection.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act - Motter, Jennifer D.; Hussain, Sarah; Brown, Diane M.; Florman, Sander; Rana, Meenakshi M.; Friedman-Moraco, Rachel; Gilbert, Alexander J.; Stock, Peter; Mehta, Shikha; Mehta, Sapna A.; Stosor, Valentina; Elias, Nahel; et al. (Transplantation, 2024)
Background. Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. Methods. Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D – [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. Results. HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D – , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D – , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). Conclusions. Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

The performance of bronchoalveolar lavage Aspergillus PCR testing in solid organ transplant recipients with invasive pulmonary aspergillosis - Mutcali, Sibel Islak; Hussain, Nadeem; Nematollahi, Saman; Lainhart, William; Zangeneh, Tirdad T.; Al-Obaidi, Mohanad M. (Transplant Infectious Disease, 2024)
Background Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. Methods We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. Results Ninety-nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non-Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty-four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%–93%), and the specificity was 98% (95% CI 93%–99%). Conclusion BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test.
Keywords: Aspergillus PCR; invasive pulmonary aspergillosis; solid organ transplant

Evaluation of valganciclovir's neutropenia risk in pediatric solid organ transplant recipients utilizing two dosing regimens - Patel, Avani; Le, Kevin; Panek, Natalia (Pediatric Transplantation, 2024)
Background: Valganciclovir is approved for cytomegalovirus prophylaxis in pediatrics using the Pescovitz algorithm. There are reports of valganciclovir overdoses in children with low body surface area and overestimated creatinine clearance utilizing this algorithm. This study compared the incidence of neutropenia and cytomegalovirus infection between the Pescovitz and weight-based dosing algorithms. Methods: A single-center retrospective chart review from January 2010 to September 2018 was performed on pediatric heart, liver, and kidney transplant recipients, who received valganciclovir. Data were collected from the initiation of valganciclovir prophylaxis to 30 days after discontinuation. The primary objective was the incidence of neutropenia in patients receiving valganciclovir dosed by the Pescovitz versus weight-based dosing algorithms. Results: This study included 187 pediatric transplant recipients who received valganciclovir dosed via the Pescovitz (62 recipients) or weight-b ased dosing algorithms (125 recipients). The incidence of neutropenia was higher in the Pescovitz (69.4%) compared to the weight-based dosing group (53.6%; p = .04) including moderate and severe neutropenia. Cytomegalovirus viremia was not significantly different between the two groups and occurred in 4.8% of the Pescovitz group compared to 2.4% of the weight-b ased group (p = .4). Conclusions: The incidence of neutropenia was greater in recipients receiving valganciclovir dosed via the Pescovitz algorithm compared to the weight-b ased dosing. There were no significant differences in regard to cytomegalovirus viremia or disease between the two groups.

AGA Clinical Practice Guideline on Fecal Microbiota–Based Therapies for Select Gastrointestinal Diseases - Peery, Anne F.; Kelly, Colleen R.; Kao, Dina; Vaughn, Byron P.; Lebwohl, Benjamin; Singh, Siddharth; Imdad, Aamer; Altayar, Osama (Gastroenterology, 2024)

Interpreting and managing preservation fluids positive for Gram-negative bacteria - Peghin, Maddalena; Graziano, Elena; Grossi, Paolo Antonio (Current Opinion in Infectious Diseases, 2024)
Culturing preservation fluids is a further step into preventing donor-derived infections. Interpreting and managing GNB positivity require a multidisciplinary team with specific skills. Standardized randomized trials are needed for insight into the real utility of preservation fluids cultures, the role of preservation fluids positivity, and the impact of antimicrobial therapy.

Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis - Pennington, Kelly M.; Martin, Max J.; Murad, M. Hassan; Sanborn, David; Saddoughi, Sahar A.; Gerberi, Danielle; Peters, Steve G.; Razonable, Raymund R.; Kennedy, Cassie C. (Transplantation, 2024)
Background. Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. Methods. We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. Results. We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. Conclusions. Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

Kidney Function Assessment Using Cystatin C and Serum Creatinine in Heart Transplantation Recipients: Implications for Valganciclovir Dosing - Pinsino, Alberto; Jennings, Douglas L; Ladanyi, Annamaria; Duong, Phuong; Sweat, Austin O; Mahoney, Ian; Bohn, Bruno; Demmer, Ryan T; Takeda, Koji; Sayer, Gabriel T; Uriel, Nir; Leb, Jay S; et al. (The Journal of Heart and Lung Transplantation, 2024)

Kidney transplantation in patients on anti-tubercular therapy: A single centre observational study - Prasad, Pallavi; Bagai, Sahil; Prasad, Vandana; Grover, Rahul; Chhabra, Gagandeep; Khullar, Dinesh (Transplant Infectious Disease, 2024)
Background Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT). Methods This was a retrospective single-center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT. Results Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosed by ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post-transplantation fluoroquinolone-based non-rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post-transplantation was 71.9, 64.7, and 67 mL/min/1.73m2, respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%. Conclusion Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase of ATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB.
Keywords: anti-tubercular therapy; transplantation; tuberculosis

The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III – Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring - Preiksaitis, Jutta; Allen, Upton; Bollard, Catherine M.; Dharnidharka, Vikas R.; Dulek, Daniel E.; Green, Michael; Martinez, Olivia M.; Metes, Diana M.; Michaels, Marian G.; Smets, Françoise; Chinnock, Richard E.; Comoli, Patrizia; et al. (Pediatric Transplantation, 2024)
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of “viremia” to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.
Keywords: Epstein-Barr virus; PTLD; biomarkers; child; solid organ transplantation

Cytomegalovirus related hospitalization costs among hematopoietic stem cell and solid organ transplant recipients treated with maribavir versus investigator-assigned therapy: A US-based study - Schultz, Bob G.; Bullano, Michael; Paratane, Deepika; Rajagopalan, Krithika (Transplant Infectious Disease, 2024)
Background Cytomegalovirus (CMV) infections among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients impose a significant health care resource utilization (HCRU)-related economic burden. Maribavir (MBV), a novel anti-viral therapy (AVT), approved by the United States Food and Drug Administration for post-transplant CMV infections refractory (with/without resistance) to conventional AVTs has demonstrated lower hospital length of stay (LOS) versus investigator-assigned therapy (IAT; valgancilovir, ganciclovir, foscarnet, or cidofovir) in a phase 3 trial (SOLSTICE). This study estimated the HCRU costs of MBV versus IAT. Methods An economic model was developed to estimate HCRU costs for patients treated with MBV or IAT. Mean per-patient-per-year (PPPY) HCRU costs were calculated using (i) annualized mean hospital LOS in SOLSTICE, and (ii) CMV-related direct costs from published literature. Probabilistic sensitivity analysis with Monte-Carlo simulations assessed model robustness. Results Of 352 randomized patients receiving MBV (n = 235) or IAT (n = 117) for 8 weeks in SOLSTICE, 40% had HSCT and 60% had SOT. Mean overall PPPY HCRU costs of overall hospital-LOS were \67,205 (95% confidence interval [CI]: \33,767, \231,275) versus \145,501 (95% CI: \62,064, \589,505) for MBV and IAT groups, respectively. Mean PPPY ICU and non-ICU stay costs were: \32,231 (95% CI: \5,248, \184,524) versus \45,307 (95% CI: \3,957, \481,740) for MBV and IAT groups, and \82,237 (95% CI: \40,397, \156,945) MBV versus \228,329 (95% CI: \94,442, \517,476) for MBV and IAT groups, respectively. MBV demonstrated cost savings in over 99.99% of simulations. Conclusions This analysis suggests that Mean PPPY HCRU costs were 29%–64% lower with MBV versus other-AVTs.
Keywords: cost-savings; cytomegalovirus infection; healthcare resource utilization; maribavir; organ transplant recipients

Clinical utility of plasma microbial cell-free DNA sequencing in determining microbiologic etiology of infectious syndromes in solid organ transplant recipients - Shah, Jesal R.; Sohail, Muhammad Rizwan; Lasco, Todd; Goss, John A.; Mohajer, Mayar Al; Khalil, Sarwat (Therapeutic Advances in Infectious Disease, 2024)
Background: Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking. Objectives: To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR. Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke’s Medical Center from March 2017 to February 2023. Methods: Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA results with clinical diagnosis. A descriptive analysis of the patient and clinical characteristics was performed. Results: A total of 113 mcfDNA tests in liver (42%), kidney (35%), lung (20%) and heart (13%) transplant recipients were performed in the study period. The most common clinical syndromes were pneumonia (36%), fever of unknown origin (16%), and intra-abdominal infections (15%). Most (80, 71%) of the mcfDNA test results were positive for microorganisms. Twenty-seven (24%) cases were classified as positive clinical impact, 82 (73%) were neutral and 4 (3%) were negative, respectively. Conclusion: In SOTR, mcfDNA sequencing can add a positive clinical impact in a quarter of the cases and identify microorganisms beyond conventional microbiological testing across clinical syndromes. The negative clinical impact was rare. However, larger prospective studies are needed to define the optimal timing and utilization of mcfDNA in the sequence of diagnostic evaluation for syndrome-specific workup in SOTR. Summary: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool that can identify difficult-to-detect microorganisms in SOTR. Our study demonstrates that the mNGS test resulted in a positive clinical impact in 1 out of 4 patients. , Plain language summary Use of plasma cell-free DNA testing to diagnose microbiologic causes of infections in solid organ transplant recipients In our study, we evaluated the use of metagenomic next-generation sequencing (mNGS) in solid organ transplant patients who were hospitalized with concerns for infection that was difficult to diagnose by standard methods of testing. We reviewed 113 patients and found that the most common syndromes in which mNGS aided in diagnosis was pneumonia (36%), followed by fever of unknown origin (16%), and intra-abdominal infections (15%). The test result was found to be positive in 80 patient for at least one or more microorganisms. Based on the standardized clinical definitions to look at the impact of obtaining mNGS test, we found that the test had a positive clinic impact in 24% of the patients, neutral impact in 73%, and a minimal negative impact of 3%, respectively. This study shows that mNGS can be helpful in appropriately managing infections in one out of four patients with solid organ transplant.

Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies - Shahid, Zainab; Jain, Tania; Dioverti, Veronica; Pennisi, Martina; Mikkilineni, Lekha; Thiruvengadam, Swetha Kambhampati; Shah, Nirali N; Dadwal, Sanjeet; Papanicolaou, Genovefa; Hamadani, Mehdi; Carpenter, Paul A.; Alfaro, Gabriela Maron; et al. (Transplantation and Cellular Therapy, 2024)

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation - Stewart, Adam G.; Kotton, Camille N. (Transplantation, 2024)
Cytomegalovirus (CMV) is one of the most common infections occurring after solid organ transplantation. This high burden of disease, which incurs sizeable morbidity, may be worsening with the proportion of high-risk D+/R− solid organ transplantation recipients increasing in some regions globally. Cohort studies continue to support either universal prophylaxis or preemptive therapy as effective prevention strategies. Letermovir prophylaxis was noninferior to valganciclovir in adult high-risk D+/R− kidney transplant recipients with fewer drug-related adverse events in a recent clinical trial and has now been approved for such use in some regions. Maribavir preemptive therapy failed to demonstrate noninferiority when compared with valganciclovir in hematopoietic stem cell transplant recipients but looked promising for safety. Donor matching could be useful in prevention CMV disease with a survival advantage demonstrated in seronegative recipients waiting up to 30 mo for a seronegative kidney. Immune-guided prophylaxis resulted in fewer CMV infection episodes in lung transplant recipients when compared with fixed-duration prophylaxis in a recent clinical trial. For treatment of refractory or resistant CMV infection, maribavir was more efficacious and better tolerated when compared with investigator-initiated therapy in its registration trial for this condition. Further research regarding best treatment and prophylaxis of resistant or refractory CMV infection is needed to reflect best clinical practice choices. Optimal use of immune globulin or CMV-specific T cells for prevention or treatment of CMV disease remains undefined. Standardized definitions for the design of CMV clinical trials have been developed. In this review, we highlight recent updates in the field from data published since 2018.

The EBMT Handbook: Hematopoietic Cell Transplantation and Cellular Therapies - Sureda, Anna; Corbacioglu, Selim; Greco, Raffaella; Kröger, Nicolaus; Carreras, Enric (Springer International Publishing, 2024)

The EBMT Handbook: Hematopoietic Cell Transplantation and Cellular Therapies - Sureda, Anna; Corbacioglu, Selim; Greco, Raffaella; Kröger, Nicolaus; Carreras, Enric (Springer International Publishing, 2024)

Epstein–Barr virus‐associated post‐transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States - Tajima, Tetsuya; Martinez, Olivia M.; Bernstein, Daniel; Boyd, Scott D.; Gratzinger, Dita; Lum, Grant; Sasaki, Kazunari; Tan, Brent; Twist, Clare J.; Weinberg, Kenneth; Armstrong, Brian; Desai, Dev M.; et al. (Pediatric Transplantation, 2024)
Abstract Background Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. Methods The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre‐transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. Results The uni−/multivariable competing risk analyses revealed the combination of EBV‐seropositive donor and EBV‐naïve recipient (D+R−) was a significant risk factor for PTLD development (sub‐hazard ratio: 2.79 [1.34–5.78], p = .006) and EBV DNAemia (2.65 [1.72–4.09], p < .001). Patients with D+R− were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations ( p = .02). Patients with monomorphic/polymorphic PTLD ( n = 21) had significantly more EBV DNAemia than non‐PTLD patients ( p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias ( p < .001), within 6‐month post‐transplant. Among non‐liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant ( p = .01). Conclusions D+R− is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow‐up of EBV viral load within 6‐month post‐transplant, especially for patients with D+R− and/or non‐liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

New Insights Into Infections’ Risk of Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia - Trimbour, Camille; Balsat, Marie; Olivier, Laura; Mihalcea, Ana-Raluca; Garnier, Nathalie; Kebaili, Kamila; Sirvent, Nicolas; Dupont, Damien; Fuhrmann, Christine; Theron, Alexandre; Domenech, Carine (Pediatric Infectious Disease Journal, 2024)
Background: This study aims to compare the infections’ risk between adolescents and young adults (AYAs), treated for acute lymphoblastic leukemia, and pediatric population. We also focused on their bacterial and fungal infection specificities. Methods: This case–control study investigated the occurrence of bacterial bloodstream infection (BSI) and proven and probable invasive fungal infection (IFI) in AYAs (15–25 years old) and children (1–14 years old) treated for acute lymphoblastic leukemia between January 2013 and December 2020 in 2 French tertiary pediatric and 2 referral adult hematological centers, independent of their treatment protocol. We also evaluated the impact of these infections on morbidity (necessity of intensive care) and mortality. Results: We analyzed 83 AYAs and 230 children and found that AYAs developed significantly more IFI than the pediatric population (22% vs. 10%, P = 0.007), regardless of their care center (adult or pediatric). Furthermore, the occurrence of BSI was similar between the 2 populations (48% vs. 51%, P = 0.66). Moreover, the occurrence of infection increased with the AYAs’ risk group of treatment: standard, medium or high risk ( P = 0.021 for BSI and P = 0.029 for IFI). Finally, the mortality rate is only 1.3% after a BSI whereas it increases to 4.9% after IFI. Conclusion: AYAs have their own specificity with an increased risk of fungal infection compared to children, independent of the care center. Antifungal prophylaxis should be contemplated, especially for patients classified in high-risk groups.

Left Ventricular Assist Devices - Vaidya, Yash; Riaz, Sana; Dhamoon, Amit S. (StatPearls, 2024)
Heart failure (HF) is a frequent cause of inpatient admissions. The Framingham study in 1993 described the risk factors for heart failure and showed unacceptably high five-year mortality rates of 25% in men and 38% in women . The American Heart Association reported the prevalence of HF to be 5.1 million in the United States in 2006 . The worldwide prevalence has been estimated to be 23 million . HF can be categorized based on the left ventricular ejection fraction (LVEF) into systolic and diastolic HF. The former group includes patients with LVEF less than or equal to 40%, also termed heart failure with reduced ejection fraction (HFrEF). Heart failure with preserved ejection fraction (HFpEF) includes those with LVEF greater than or equal to 40%.  The multiple modalities of treatment available to treat HF include but are not limited to lifestyle modifications, pharmacologic agents, device therapies such as implantable cardioverter-defibrillator (ICD), and cardiac resynchronization therapy (CRT). At times, failure to improve could necessitate short-term mechanical circulatory support with the use of an intra-aortic balloon pump (IABP) or even extracorporeal membrane oxygenation (ECMO). However, a large population of patients continues to have advanced heart failure with worsening LVEF despite maximal therapy. Circulatory support with the use of a left ventricular assist device (LVAD) is an emerging field. The landmark REMATCH trial that compared LVADs with optimal medical therapy in class IV HF patients found a 48% reduction in mortality from any cause . There was also a significant increase in the survival rates at one year (52% versus 25%) and two years (23% versus 8%). The definitive treatment for advanced HF (class II and IV) is cardiac transplantation . However, with the limited number of donor hearts available, LVADs are life-saving.

Chronic Graft-Versus-Host Disease - Wolff, Daniel; Peric, Zinaida; Lawitschka, Anita (The EBMT Handbook, 2024)
Abstract Chronic GVHD (cGVHD) is the most relevant cause of late non-relapse morbidity and subsequent mortality (approximately 25%) following allo-HCT (Grube et al. 2016). Its incidence is approximately 50% among all patients following allo-HCT and has increased during the last two decades due to increasing patient age and increasing use of unrelated and/or mismatched donors, RIC regimens, PBSC with application of standard GVHD prophylaxis (calcineurin inhibitor [CNI] + MMF or MTX) only (Arai et al. 2015). While the incidence of cGVHD is lower (6–40%) in children, its incidence rises to 60% as age increases (Baird et al. 2010; Sobkowiak-Sobierajska et al. 2022).

The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies - Zhu, Violet Z.; Horton, Miles B.; Haeusler, Gabrielle M.; Yong, Michelle K. (Current Opinion in Infectious Diseases, 2024)
The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.

Impact of an ultrasensitive Cytomegalovirus quantitative nucleic acid test on Cytomegalovirus detection and therapy in renal transplant recipients - Beechar, Vivek B.; Pouch, Stephanie M.; Phadke, Varun K.; Karadkhele, Geeta; Larsen, Christian P.; Woodworth, Michael H. (Transplant Infectious Disease, 2023)
Background: Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decisionmaking and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia. Methods: We conducted a single-center cohort study contrasting RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ >300 IU/mL) with those monitored with a more sensitive qNAT (LLOQ >35 IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R−: high risk; any R+: moderate risk). CMV viral load monitoring was performed monthly post transplantation, with the primary outcomes being time to CMV DNAemia and its duration. Results: Total 1382 patients were analyzed from 2014 to 2016 and 2019 to 2021. Moderate-risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR: 1.95, 95% confidence interval [CI]: 1.55–2.46) and an average of 24 (95% CI: 16.40–31.98) additional days of DNAemia. There was no difference in CMV end-organ disease or 1-year all-cause mortality between moderate-risk RTRs. Conclusions: The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate-risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs.

Clinical course and management of COVID-19 in the era of widespread population immunity - Meyerowitz, Eric A.; Scott, Jake; Richterman, Aaron; Male, Victoria; Cevik, Muge (Nature Reviews Microbiology, 2023)

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline - Awan, Ahmed Arslan Yousuf; Berenguer, Marina C.; Bruchfeld, Annette; Fabrizi, Fabrizio; Goldberg, David S.; Jia, Jidong; Kamar, Nassim; Mohamed, Rosmawati; Pessôa, Mário Guimarães; Pol, Stanislas; Sise, Meghan E.; Balk, Ethan M.; et al. (Annals of Internal Medicine, 2023)

Risk Factors for Surgical-Site Infections After Liver Transplant: Does Perioperative Antibiotic Regimen Matter? - Rolak, Stacey C.; Yetmar, Zachary A.; Lahr, Brian D.; Beam, Elena; Razi, Samrah; Watt, Kymberly; Yang, Liu; Aqel, Bashar A.; Mahmood, Maryam (Transplantation, 2023)
Background. Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. Methods. Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. Results. Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin–tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ–space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10–20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs ( P = 0.5), whereas surgical leak ( P <0.001) and reoperation ( P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. Conclusions. The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

Current use of fecal microbiota transfer in patients with hematologic diseases: a survey on behalf of the Cellular Therapy and Immunobiology Working Party of the EBMT - Battipaglia, Giorgia; Mooyaart, Jarl E.; Meyer, Ralf; Mohty, Mohamad; Sadowska-Klasa, Alicja; Goloshchapov, Oleg; Locatelli, Franco; Styczynski, Jan; Pavlu, Jiri; Dybko, Jaroslaw; Bronin, Gleb; Salmenniemi, Urpu; et al. (Bone Marrow Transplantation, 2023)
Keywords: Diseases; Haematological cancer

A joint program of antimicrobial stewardship and hospital-acquired infection control to reduce healthcare-associated infections after kidney transplantation: The Hipomenes study - Silva, José Tiago; Montoro, Juan; Pérez-Jacoiste Asín, María Asunción; Fernández-Ruiz, Mario; Polanco, Natalia; González, Esther; Caro-Teller, José Manuel; Andrés, Amado; Aguado, José María; López-Medrano, Francisco (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2023)
Infection is a common complication in kidney transplant recipients (KTRs). The usefulness of antimicrobial stewardship programs (ASP) and hospital-acquired infection control (HAIC) initiatives in the general inpatient population is well established. We performed a quasi-experimental study to evaluate a joint ASP/HAIC initiative focused on KTRs. A dedicated ASP team optimized antimicrobial prescriptions in consecutive KTRs during the intervention period (June 2015-March 2016). A multifaceted, evidence-based HAIC program was concurrently implemented. Results were compared with the preceding period (June 2014-March 2015). We included 96 and 100 KTRs in the intervention and preintervention periods, respectively. There was a reduction in the consumption of meropenem (rate ratio [RR]: 0.63; 95% confidence interval [CI]: 0.53-0.75; P <.0001), ceftazidime (RR: 0.31; 95% CI: 0.21-0.45; P <.0001), vancomycin (RR: 0.65; 95% CI: 0.53-0.8; P <.0001), and ciprofloxacin (RR: 0.66; 95% CI: 0.55-0.81; P <.0001) and an increase of fosfomycin (RR: 1.80; 95% CI: 1.17-2.76; P =.008) during the intervention period. The incidence of cystitis (RR: 0.30; 95% CI: 0.28-0.33; P <.001) and upper urinary tract infection (RR: 0.56; 95% CI: 0.33-0.95; P =.04) decreased. A specific ASP/HAIC initiative was effective in optimizing antimicrobial use and reducing the incidence of common bacterial infections among KTRs.
Keywords: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Stewardship; Cross Infection; Delivery of Health Care; Hospitals; Humans; Infection Control; Kidney Transplantation; antimicrobial prescription; antimicrobial stewardship; hospital-acquired infection; kidney transplantation; multidrug-resistant bacteria

Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir with Valganciclovir - Papanicolaou, Genovefa A; Avery, Robin K; Cordonnier, Catherine; Duarte, Rafael F; Haider, Shariq; Maertens, Johan; Peggs, Karl S; Solano, Carlos; Young, Jo-Anne H; Fournier, Martha; Murray, Rose Ann; Wu, Jingyang; et al. (Clinical Infectious Diseases, 2023)
Background. Neutropenia may limit use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir. Methods. In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks follow-up. Primary T endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). Key secondary endpoint was a composite of the primary endpoint IP with no findings of CMV tissue-invasive disease at week 8, through week 16. Treatmentemergent adverse events (TEAEs) were assessed. R Results. Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of C non-inferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted S difference [95% confidence interval (CI)]: −7.7% [−14.98, −0.36]; lower limit of 95% CI of treatment difference exceeded −7.0%). At week 16, 52.7% and 48.5% of patients treated U (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissueinvasive disease (adjusted difference [95% CI]: 4.4% [−3.91, 12.76]). With maribavir (versus N valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due A to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, M 4.0%; valganciclovir, 17.5%). Conclusions. Although non-inferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified non-inferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer D discontinuations due to neutropenia.

Two-Week Direct-Acting Antiviral Prophylaxis for Kidney Transplantation From Donors With Hepatitis C Viremia to Recipients Without Hepatitis C Viremia: A Small Uncontrolled Trial - Desai, Niraj M.; Leung, Sherry G.; Motter, Jennifer D.; Segev, Dorry L.; Warren, Daniel; Durand, Christine M. (Annals of Internal Medicine, 2023)

Hepatitis E virus infection epidemiology in allogeneic hematopoietic cell transplant recipients - Courjon, Johan; Portillo, Vera; Yerly, Sabine; Vetter, Pauline; Schibler, Manuel; Mappoura, Maria; Morin, Sarah; Giannotti, Federica; Mamez, Anne-Claire; van Delden, Christian; Kaiser, Laurent; Chalandon, Yves; et al. (Open Forum Infectious Diseases, 2023)
Among 292 allogeneic hematopoietic cell transplant recipients (allo-HCTr, 2018-2022), 64 (21.9%) tested positive for anti-HEV-IgG and among 208 allo-HCTr tested by plasma/serum-HEV-PCR (2012-2022) 3 (1.4%) primary HEV infections were diagnosed; in one patient plasma HEV-PCR relapsed positive for 100 days. HEV infection remains rare albeit associated with persistent viral replication.

Liver Transplantation - Lucey, Michael R.; Furuya, Katryn N.; Foley, David P. (New England Journal of Medicine, 2023)

Routine infectious disease consultation prior to an allogeneic hematopoietic cell transplant - Portillo, Vera; Masouridi-Levrat, Stavroula; Chalandon, Yves; Mappoura, Maria; Morin, Sarah; Marinosci, Annalisa; Giannotti, Federica; Mamez, Anne-Claire; van Delden, Christian; Neofytos, Dionysios (Open Forum Infectious Diseases, 2023)
A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic-hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations.We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an allogeneic-HCT between 2018 and 2022 in 292 adult (≥18-year-old) consecutive patients. We describe the performance of a TID consultation, arbitrarily defined as major (HCT-postponement, procedure, cytomegalovirus recipient (CMV-R) serology reinterpretation) and minor interventions.Overall, 765 interventions were observed in 257/292 (88%) patients: 88/765 (11.5%) major and 677/765 (88.5%) minor interventions. Amongst major interventions, HCT was postponed in 8/292 (2.7%) patients and a procedure was requested in 18/292 (6.2%) patients. The CMV-R serostatus was changed from indeterminate/low-titer positive to negative in 60/292 (20.5%) patients. Amongst 677 minor interventions, there were: 68 (8.8%) additional consultations with other services requested, 260 (33.7%) additional diagnostic tests requested, 102 (13.2%) additional treatments recommended, 60 (7.8%) non-CMV serology reinterpretations performed, 115 (14.9%) deviations from routine anti-infective prophylaxis, and 72 (9.3%) deviations from routine empirical antibiotic treatment recommendations in case of neutropenic fever.We are proposing a structured, clearly defined, and comprehensive pre-transplant checklist for an effective assessment of ID risks and complications prior to an allogeneic-HCT. Further studies or experiences like ours could help to define a global strategy or new models of care to be implemented in HCT centers in the future.

Use and Outcomes of Hepatitis B Virus-Positive Grafts for Kidney or Heart Transplantation in the United States From 1999 to 2021 - Singal, Ashwani K.; Reddy, K. Rajender; Nguyen, Mindie H.; Younossi, Zobair; Kwo, Paul; Kuo, Yong-Fang (Transplantation, 2023)
Background. The gap between demand and supply for solid organ transplants requires strategies to expand the donor pool. Successful use of hepatitis B virus (HBV)-positive grafts has been reported in liver transplantation. Methods. In this United Network for Organ Sharing database (January 1999 to June 2021) retrospective cohort study, outcomes of kidney transplant (KT) or heart transplant (HT) recipients with HBV donor grafts (hepatitis B surface antigen and/or for HBV nucleic acid test-positive) were examined. Propensity score matching was performed for HBV-positive to negative graft recipients (1:5 for renal transplantation and 1:10 for HT). Results. Of 448 HBV-positive donors with 896 kidneys, 352 kidneys (39.3%) and 56 hearts (12.5%) were transplanted. Of these, 312 kidneys (88.6%) and 45 hearts (80.3%) were transplanted in hepatitis B surface antigen-negative recipients. Ten-year graft survival was 47.1% and 49% (log-rank P = 0.353), and patient survival was 58% and 59% ( P = 0.999) for KT recipients. Similar figures among HT recipients were 41.9% and 38.9% for graft survival ( P = 0.471), and 54.3% and 61.2% for patient survival ( P = 0.277). Subgroup analyses in recipients with HBV nucleic acid test-positive grafts irrespective of antibodies to HBV core antigen-positive status, and recipients negative for anti-HBs (548 renal transplantation and 209 HT) were similar. Conclusions. Although we are limited by lack of available data on posttransplant anti-HBV treatment, the study observations suggest that using HBV-positive grafts is a reasonable strategy to expand the donor pool among candidates waiting for KT or HT.