Transplant Infectious Disease最新文献

A successful multidisciplinary research center depends on the quality of the science being conducted and the quality of the center's design, culture, infrastructure, and institutional support. In this perspective, we describe our experience building and maintaining a multidisciplinary transplant research center with a large focus on transplant infectious diseases. We identify principles that we believe contributed to our success including: taking inventory, defining culture, creating a multidisciplinary shared leadership model, establishing expertise in a multiple method approach, investing in operations and management, building and sharing resources, and securing institutional support. We share our experience putting these principles into practice and highlight potential roadblocks.

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.

Introduction: BK polyomavirus (BKPyV)-DNAemia is a common complication in kidney transplant recipients (KTRs). The significance of achieving viral clearance at different time intervals is not well understood.

Methods: All adult KTRs transplanted between January 1, 2015 and December 31, 2017 who developed BKPyV-DNAemia were included. Outcomes were analyzed based on persistent clearance of BKPyV-DNAemia at 3-month intervals up to 2 years after initial detection, and for recipients with persistent BKPyV-DNAemia at last follow-up. Uncensored graft failure, death-censored graft failure (DCGF), and a composite outcome of DCGF or fall in estimated glomerular filtration rate (eGFR) by ≥50% from the time of initial BKPyV-DNAemia were outcomes of interest.

Results: Of 224 KTRs with BKPyV-DNAemia, 58 recipients (26%) achieved viral clearance by 3 months after initial detection, 105 (47%) by 6 months, 120 (54%) by 9 months, 141 (63%) by 12 months, 155 (69%) by 15 months, 167 (75%) by 18 months, 180 (80%) by 21 months, and 193 (86%) by 24 months. Nine recipients (4%) had persistent BKPyV-DNAemia at last follow-up. Compared to recipients who achieved viral clearance by 3 months, those who achieved clearance by 6 months (adjusted odds ratio [aOR]: 3.15; 95% confidence interval [CI]: 1.22-8.12; p = .02) and 9 months (aOR: 3.69; 95% CI: 1.02-13.43; p = .04) had significantly increased risk for uncensored graft failure. There was no significant association between time to viral clearance and DCGF or composite outcomes.

Conclusions: We found a trend of increased risk for uncensored graft failure among those who cleared BKPyV-DNAemia more slowly. Aiming to clear viremia early, without risking rejection, may be beneficial for allograft function and patient morbidity and mortality.

Background: There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant.

Methods: Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections.

Results: 102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups.  CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.

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: Cytomegalovirus (CMV) contributes to morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pre-emptive antiviral therapy (PET) reduces the incidence of CMV end-organ disease (EOD), though relevant viral thresholds to initiate PET remain undefined. We evaluated the impact of viral loads (VLs) at PET initiation on virologic and clinical outcomes following pediatric allo-HCT.

Methods: Single-center retrospective cohort analysis of children who underwent their first allo-HCT from January 2014 to December 2020. Weekly quantitative plasma CMV polymerase chain reaction was performed until Day +100 and PET was initiated once VL exceeded a pre-defined threshold per institutional guidelines. Patients were followed for 1-year post-HCT to evaluate virologic and clinical outcomes including end-organ disease (EOD), overall survival (OS), and non-relapse mortality (NRM).

Results: Among 146 allo-HCT recipients, CMV DNAemia occurred in 40 patients (27%) at a median of 15 days post-HCT (interquartile range 6-28.5). Ten percent (n = 4) had spontaneous resolution of DNAemia, while 90% (n = 36) required PET. PET initiated when CMV VL was ≥ 1000 IU/mL (n = 21) vs when VL < 1000 IU/mL (n = 15) resulted in higher peak CMV VL (12,670 vs. 1284 IU/mL, p = 0.0001) and longer time to CMV DNAemia resolution (36 vs. 24 days, p = 0.035). There were no differences in EOD, OS, or NRM at 12 months post-HCT based on VL at PET initiation.

Conclusions: Initiating PET when CMV VL was ≥1000 IU/mL resulted in significantly higher peak VL and prolonged DNAemia, with no differences in EOD, OS, or NRM at 12 months post pediatric HCT.

Background: Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT.

Methods: A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation.

Results: The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups.

Conclusions: A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT.

Background: Cytomegalovirus (CMV) mismatched, donor IgG-positive/recipient IgG-negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post-prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post-prophylaxis disease.

Methods: This was a single-center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post-prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5-year mortality based on DNAemia pattern stratified by organ transplant type.

Results: Post-prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non-lung recipients (p =  .003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5-year mortality.

Conclusion: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long-term mortality.