Transplant Infectious Disease最新文献

Background: Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment.

Methods: We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI.

Results: Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant-days; p =  .8) and multidrug-resistant gram-negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant-days; p =  .08) were not significantly higher in comparison to patients who did not receive moxifloxacin.

Conclusion: A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.

This paper is an educationally focused article discussing how transplant infectious diseases (TID) providers balance the risks of accepting or rejecting an organ and have pushed barriers in organ transplantation. We emphasize the role TID providers play in the transplantation process as critical players on the transplant team. We discuss various donor-derived infections that were previously deemed unacceptable for donation due to concerns for transmission. Advances in medical knowledge have changed some of these situations. We discuss the critical role TID providers have in closing the gap between the thousands of patients on organ waitlists and the organ deficit faced each day. We believe TID providers have a unique opportunity to expand the donor pool by increasing education, expanding acceptable organ definitions, and expanding the boundaries of what we can do with potentially transmissible infections in organ transplantation.

Introduction: Cytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high-risk recipients. However, delayed-onset post-prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post-HSCT.

Methods: Retrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event.

Results: Among 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty-six (15.7%) developed a breakthrough csCMVi. Delayed-onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed-onset csCMVi (OR 0.23).

Conclusions: Having a matched unrelated donor, a CMV donor negative/recipient positive status, and a non-AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients.

Aim: Often, organ transplantation is the only option to improve the life expectancy and quality of life of patients with terminal organ failure. Despite improved donor and organ assessment, a residual risk remains for transmitting infection, tumor, or other disease from the donor to recipients. Analysis, reporting, and managing of donor-derived diseases through a vigilance and surveillance system (V&S) is mandatory in many countries. We report on suspected and proven/probable donor-derived infections (DDI) in Germany over a period of 8 years (2016-2023).

Methods: All incoming serious-adverse-event and serious-adverse-reaction (SAE/SAR) reports from 01.01.2016 to 31.12.2023 were evaluated for suspected DDI. Analysis of imputability followed the definition of the US Disease Transmission Advisory Committee (DTAC). Only probable and proven cases according to DTAC classification were defined as DDI.

Results: During the study period, 9771 donors in Germany donated post-mortem organs to 27 919 recipients. In that period 612 SAE/SAR cases were reported, 377 (62%) involved infections. 41 cases were proven/probable DDI affecting 58 recipients (seven recipients died, 12%). Suspected infections were bacterial (182/377, 48%), fungal (135/377, 36%), viral (55/377, 15%), and parasitic (5/377, 1%). In case of bacterial DDI, no recipient died, but organ loss occurred in six recipients. In case of fungal or viral DDI, 19% (3/16) and 21% (3/14) of the recipients died, respectively.

Conclusions: DDI are rare in solid organ transplantation (58/27 919, 0.21%), but when they occur, they are associated with high morbidity and mortality in affected recipients. Careful and detailed donor evaluation and a reliable V&S help improve recipient safety.

Background: Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.

Methods: Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post-transplant follow-up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.

Results: Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work-up for suspected infection during hospitalization. After a median follow-up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post-transplant and >2 years post-transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.

Conclusion: Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region.

Background: Chimeric antigen receptor (CAR) T-cell therapy is an emerging therapeutic modality for relapsed and refractory hematological malignancies. Infectious complications following CAR T-cell therapy are not well defined.

Methods: This is a retrospective analysis of data on patients who received CAR T-cell therapy between April 2018 and December 2022 at the Karmanos Cancer Center, Detroit. Patients' data were collected up to their last known clinic or inpatient follow-up visit. An infectious episode was defined as any microbiologically proven or clinically documented infection.

Results: Seventy-six patients received therapy with FDA-approved CAR T-cell products. Thirty-three patients (43.4%) had at least one infectious episode. There were 61 infectious episodes during a median follow-up of 184 (96-340) days. Median duration for the onset of infection was 59 (22-209) days. Bacterial and viral infections occurred in 42.6% and 41% of the infectious episodes, respectively. COVID-19 was the most common infectious complication (14.8%). Time-to-event analysis showed that most infections occurred within the first 100 days. Empirical antibiotic use during Cytokine Release Syndrome/Immune effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) in the absence of documented bacterial infection was reported in 85.7% of patients. Clostridioides difficile accounted for 11.5% of all infectious episodes. Five of six patients with C. difficile infection had CRS/ICANS and received antibiotics.

Conclusion: COVID-19 and C. difficile infection were the most common infections following CAR T-cell therapy. Most infections occurred within the first 100 days. Empiric antibiotic use and C. difficile infection were common in patients with CRS/ICANS, in the absence of documented bacterial infection, thus providing an excellent opportunity for antimicrobial stewardship in this population.