Transplant Infectious Disease最新文献

Background: Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate.

Methods: We present a single-center cohort study describing a 10-year experience of kidney transplantation in patients at risk of donor-derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR).

Results: Fifty-seven kidney transplant recipients (KTRs) were enrolled in the study. Forty-four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory-detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1-year post-transplantation, the patient and graft survival rates were 96.5% and 93%, respectively.

Conclusion: In this study, no donor-derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis.

Background: In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)-negative (-) recipients who received HCV NAT-positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT- recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution.

Methods: This was an Institutional Review Board-approved, single-center, retrospective case-control study of HCV NAT- kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation.

Results: A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT-) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95-1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient-, D+/R-).

Conclusion: Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV.

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.

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.

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.

Background: Bacteremia is a common complication in allogeneic hematopoietic cell transplant recipients (alloHCTr), especially during the pre-engraftment period. International guidelines recommend antibacterial prophylaxis (ABP), despite potential selection for multidrug-resistant organisms (MDRO). Limited contemporary data exist on the epidemiology of pre-engraftment bacteremia in alloHCTr, who do not receive ABP.

Methods: We performed a retrospective observational single-center cohort study including all consecutive adult alloHCTr (2015-2021), investigating the incidence, risk factors, and outcomes of bacteremia during the engraftment period. Primary fluoroquinolone (FQ) ABP is not routinely administered in our center.

Results: Among 421 patients identified, 124 bacteremia episodes were observed in 121/421 (29%) alloHCTr. The median time to the 1st bacteremia episode was 9 days (IQR 6-11). Most (105/124, 85%) episodes were monomicrobial, while >1 pathogens were identified in 19/124 (15%) episodes. Overall, 152 pathogens were isolated, with a predominance of Gram-positive (118/152, 78%), including coagulase-negative staphylococci (n:47), streptococci (n:46), and enterococci (n:15), followed by Gram-negative bacteria (GNB, 30/152, 20%), and anaerobes (4/152, 3%). There were 2/152 (1%) MDRO (extended-spectrum beta-lactamase producing) GNB. Multivariable analyses identified age >40-year-old (OR 2.4, P = 0.02), male gender (OR 1.8, P = 0.02), and a haploidentical/mismatched unrelated donor (OR 2.5, P < 0.001) as independent risk factors for bacteremia. All cause 30-day mortality among alloHCTr with bacteremia was 0.8% (1/121): one patient died due to an HCT-related complication.

Conclusion: Despite lack of primary FQ ABP, low rates of bacteremia were observed during the pre-engraftment period, with low MDRO prevalence and mortality. Our findings may allow to revisit the need for primary universal FQ ABP in high-risk neutropenic hematology patients.