Transplant Infectious Disease最新文献

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.

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.

Solid organ transplant and hematopoietic cell transplant patients face an increased risk of infectious diseases, greater exposure to antibiotics, and heightened risk of multidrug-resistant organisms (MDROs) due to their immunosuppressed state. Antimicrobial stewardship programs (ASP) are essential in reducing the incidence of MDRO by conserving antimicrobial use, minimizing treatment durations, and improving the appropriate use of diagnostic testing. However, the role of ASP in transplant infectious diseases (TID) is still evolving, necessitating greater collaboration between ASP and transplant programs. This collaboration will mitigate infection risks, reduce infection-associated costs, and improve outcomes. This article reviews the key components for implementing ASP in TID, especially for those that are establishing or growing their ASP to include TID, including specific goals, structure and funding, ASP initiatives (including antibiotic allergy delabeling, diagnostic stewardship, and antiviral/antifungal stewardship), metrics, and educational opportunities.

Background: Treatment strategies for BK polyomavirus (BKPyV) infection in kidney transplant recipients are heterogeneous among clinicians. We aimed to identify the treatment preferences of key stakeholders for BKPyV infection and measure the trade-offs between treatment outcomes.

Methods: Adult kidney transplant recipients, caregivers, and clinicians were eligible to participate in a discrete choice experiment between February 2021 and June 2022. The five treatment-related attributes were achieving viral clearance and optimal graft function, as well as reducing the risk of graft loss, acute rejection, and complications. Results were analyzed using multinomial logistic models.

Results: In total, 109 participants (57 kidney transplant recipients, 10 caregivers, and 42 health professionals) were included. The most important attribute was the risk of graft loss, followed by side effects and acute rejection. As the risk of graft loss increased, all participants were less inclined to accept an assigned treatment strategy. For instance, if graft loss risk was increased from 1% to 50%, the probability of uptake of a treatment strategy for BKPyV infection was reduced from 87% to 3%.

Conclusion: Graft loss is the predominant concern for patients, caregivers, and health professionals when deciding on the treatment for BKPyV infection, and should be included in intervention trials of BKPyV infection.

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.

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: Hematopoietic cell transplant (HCT) survivorship care includes recommendations for post-HCT revaccination to restore immunity to vaccine-preventable diseases (VPDs). However, not all survivors agree to be vaccinated. No existing studies have comprehensively reported barriers and facilitators to adult HCT survivors completing revaccination.

Methods: A cross-sectional survey of 194 adult HCT survivors was analyzed using convergent mixed methods. The analysis used various statistical methods to determine the prevalence of barriers and facilitators and the association between revaccination and the number and specific type of barriers and facilitators. Content analysis was applied to open-ended item responses. Integrated analysis merged quantitative and qualitative findings.

Results: The most frequent barriers included the inability to receive live vaccines because of immunosuppression, identifying a suitable community location for administering childhood vaccines to adults, and delayed immune recovery. The most frequent facilitators were having healthcare insurance and a clear calendar of the revaccination schedule. Complete revaccination rates were lower with each additional reported barrier (OR = 0.58; 95% CI 0.459-0.722) and higher with each additional reported facilitator (OR = 1.31; 95% CI 1.05-1.63). Content analysis suggested that most barriers were practical issues. One significant facilitator highlighted by respondents was for the transplant center to coordinate and serve as the vaccination location for revaccination services. Merged analysis indicated convergence between quantitative and qualitative data.

Conclusion: Practical barriers and facilitators played a consequential role in revaccination uptake, and survivors would like to be revaccinated at the transplant center.

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.