Transplant Infectious Disease最新文献

Background: Infections by carbapenem-resistant Pseudomonas aeruginosa (CRPA) have been associated with high morbidity and mortality among solid organ recipients.

Objectives: To delineate the epidemiological and molecular characteristics of a recurrent outbreak of imipenem (IMP)-producing P. aeruginosa (CRPA) among kidney transplant (KT) recipient METHODS: We described a recurring CRPA outbreak in a KT ward, divided into two periods: before unit closure (Feb 2019-2020) and after reopening (Aug 2020-Dec 2023). Routine surveillance cultures (SCs) were performed using axillary-perineum-rectal swabs with immunochromatographic tests. A case-control study identified risk factors for CRPA acquisition. Pulsed-field gel electrophoresis and whole genome sequencing characterized the strains.

Results: After reopening, new cases arose from patients previously colonized, peaking 18 months later. A total of 67 KT recipients with CRPA-IMP-producing strains were identified. All except one sequenced strain belonged to the ST446 clone, differing by a maximum of 110 single nucleotide polymorphisms. Forty-five (67.2%) cases were identified through SC, with 45.7% showing intermittent SC positivity. Patients remained colonized for up to 623 days. Twenty-four (35.8%) patients had infections, with the most common site being the urinary tract. Identified risk factors included older age, deceased donor, re-transplantation, reoperation, carbapenem or quinolone use, lymphopenia, hospital stay >10 days, and the first 60 days post-KT.

Conclusion: KT recipients can harbor CRPA for extended periods, and detecting CRPA-colonized patients is challenging. These characteristics highlight the patient as the major source and a critical point in outbreak control.

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.

Background: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management.

Methods: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate.

Results: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries.

Conclusion: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

Background: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV).

Methods: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow-up through day 49.

Results: The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log₁₀ reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group).

Conclusions: These preliminary results indicate that low-dose cidofovir was safe and tolerated but had no significant BKPyV-specific antiviral effect in KTRs with BKPyVAN.

Background: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients (SOTRs). Secondary prophylaxis (SP) is not routinely recommended by guidelines on the management of CMV in SOTR but may be considered in certain higher-risk situations.

Methods: A comprehensive search of English language publications up to September 2023 was performed. The primary outcome was CMV relapse, defined as the recurrence of DNAemia or disease. Secondary outcomes included graft loss, mortality, and hematological toxicity. Meta-analysis used the random-effects model. The study protocol is registered in PROSPERO (no. CRD42022357028).

Results: Six retrospective comparative studies were included. A total of 520/727 (72%) of SOTR received SP with valganciclovir. The meta-analysis did not demonstrate a significant difference in CMV relapse (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.79-2.63). Heterogeneity between the studies was low (I² = 0%, p = 0.57). SP was significantly associated with a reduction in mortality (OR 0.2, 95% CI 0.07-0.54) but not graft loss (OR 0.67, 0.17-2.63). There was no significant difference in CMV relapse among kidney-specific SOTR (OR 1.38, 95% CI 0.65-2.96).

Conclusion: Evidence from six nonrandomized studies is limited and cannot support a recommendation for or against routine SP in SOTR treated for CMV infection. Awaiting prospective-controlled trials, the decision about SP should depend on individualized risk-profile assessments by experienced clinicians.

Introduction: Vancomycin-resistant Enterococci (VRE) infections cause significant morbidity and mortality in liver transplant (LT) recipients. Management is challenging, especially in the setting of daptomycin resistance (DR).

Methods: Single-center retrospective review of patients who underwent LT between January 1, 2020, and December 31, 2022, and developed VRE infections. Descriptive statistics were used and Kaplan-Meier curves estimated freedom from treatment failure and survival.

Results: Forty-two patients (median age 58; 64% female; 67% white) were included. Alcohol-related cirrhosis (48%) and metabolic dysfunction-associated steatohepatitis (31%) were the most common indications for LT, and most were from deceased donors (86%). VRE infection occurred at a median of 21 days after LT, and 16% had known prior VRE colonization. Common infection sites were blood (45%, n = 19), intraabdominal (36%, n = 15), and urine (36%, n = 15). Most were initially treated with daptomycin alone (64%) or in combination with other agents (21%); 7% received linezolid alone. Twelve (29%) developed breakthrough infections during treatment and 11 (26%) had recurrent infections after discontinuation of treatment. All-cause mortality was 36% (n = 15) at a median of 90 days after VRE infection diagnosis and was nearly twice as high in patients with DR (63%).

Conclusion: VRE infection in LT recipients relapsed or recurred in over 25%. Mortality was high, especially in cases with DR. More data is needed to establish an optimal treatment approach, particularly for relapse and DR.