Transplant Infectious Disease最新文献

Background: Clostridioides difficile infection (CDI) is a common complication in patients receiving broad-spectrum antibiotics and causes significant morbidity, especially in solid organ transplant recipients. Oral vancomycin has shown potential for CDI prophylaxis, whereas metronidazole has been used solely for treatment; however, their effectiveness as primary prophylaxis remains uncertain. This study evaluates oral vancomycin or metronidazole prophylaxis in preventing primary CDI among lung transplant recipients (LTRs) during the index transplant admission.

Methods: We conducted a retrospective chart review of all LTRs at the University of Kentucky from January 2020 to May 2023. Patients were grouped based on whether they received primary CDI prophylaxis (oral vancomycin or metronidazole) during systemic antibiotic therapy at transplant. The primary outcome was the incidence of CDI during the index admission. Secondary outcomes included CDI incidence within 1 year post-transplant and all-cause mortality.

Results: Of 92 LTRs, 51 (55.4%) received prophylaxis and 41 (44.6%) did not. The incidence of CDI during the index admission was 2.0% (1/51) in the prophylaxis group and 2.4% (1/41) in the non-prophylaxis group. Within 1 year, CDI incidence was 5.9% versus 2.4%, respectively (p = 0.626). All-cause mortality was significantly higher in the prophylaxis group (41.2% vs. 19.5%; p = 0.041), likely reflecting greater baseline illness severity and comorbidities.

Conclusions: Primary prophylaxis with oral vancomycin or metronidazole did not reduce CDI incidence among LTRs. Prophylaxis was more frequently used in patients with prolonged hospitalizations and longer antibiotic courses. Larger studies are needed to clarify the role of primary CDI prophylaxis in this high-risk population.

Background: BK virus infection is a marker of poor immune recovery, especially after kidney or allogeneic cell transplantation. Because of the challenges associated with BK virus infection and the lack of effective treatments, there is a growing interest in novel approaches, such as adoptive cellular therapy, that aim to restore antiviral immunity and promote viral clearance.

Methods: Our clinical trial assessed the feasibility, safety, and efficacy of administering third-party, BK virus-specific cytotoxic T lymphocytes (CTLs) used to treat allogeneic HCT patients and kidney transplant patients with biopsy-proven BK-virus nephropathy. Comprehensive clinical assessments and correlative studies were performed.

Results: The study included six patients after kidney-transplantation and five HCT recipients. Viremia declined in most evaluable patients by Day 45 after BKCTL infusion. No new instances of graft-versus-host disease, kidney-transplant rejection, graft failure, or infusion-related toxicities were attributed to the treatment. Antiviral activity (as assessed by interferon-γ secretion) did not differ between infused BKV-CTLs given to kidney-transplant versus allogeneic SCT recipients.

Conclusion: In this study, we longitudinally tracked the in vivo persistence of adoptively transferred BKV-CTLs and demonstrated their sustained functional activity. This therapy could be promising in KT and SCT patients with recent-onset BK-virus viremia.

The COVID-19 pandemic exposed the vulnerability of immunocompromised hosts and the scarcity of evidence guiding their management. Within the European Horizon 2020 ORCHESTRA project, a multinational consortium connected existing and new cohorts to harmonize data, laboratory methods, and clinical expertise across fragile populations. The fragile patients' cohort became a model for how collaborative infrastructure can generate actionable evidence during a crisis. Through prospective follow-up and centralized immunologic assessment, ORCHESTRA defined the clinical spectrum of COVID-19 in transplant recipients, identified vaccine-modified disease phenotypes, and clarified the kinetics and correlates of immune protection. The project also demonstrated the feasibility of real-time immunologic monitoring, the value of data interoperability, and the need for adaptive harmonization across health systems. Integrating these results through Delphi consensus, ORCHESTRA translated research into practice, providing pragmatic guidance for clinicians across Europe. This experience underscores that harmonized, multidisciplinary research-rooted in collaboration and flexibility-can transform variability into knowledge and ultimately improve care for the most immunologically fragile patients.

The incidence of HHV-8/KSHV-associated diseases (KADs) among solid organ transplant (SOT) recipients has shown a relative increase, likely reflecting the growing population of long-term SOT survivors and heightened recognition and reporting due to greater clinician awareness. The real impact of HHV-8/KSHV in the SOT setting remains difficult to determine due to regional variations in seroprevalence and non-universal screening practices. Neoplastic KAD reported in SOT includes Kaposi sarcoma (KS), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and other rare lymphomas. Increasing attention has focused on Kaposi's Sarcoma-associated Herpesvirus Inflammatory Cytokine Syndrome (KICS), a non-malignant syndrome characterized by uncontrolled inflammation, fever, pancytopenia and elevated HHV-8/KSHV DNAemia, resembling viral sepsis that can progress to shock and multi-organ failure. A clinical protocol including testing donors and recipients, monitoring for DNAemia in recipients at risk, switching CNI to mTOR inhibitors, treatment with antivirals, and rituximab for KICS may mitigate the impact of HHV-8/KSHV infection in SOT recipients. However, standardized serological testing is not available and the role of monitoring, preemptive management and treatment of HHV-8/KSHV DNAemia should be studied in larger prospective studies. Severe donor-derived KICS and KS, often presenting without skin involvement, underscore the need for reliable serologic tests for identification of at-risk recipients (especially D+/R-), heightened clinical awareness to ensure timely diagnosis and prompt treatment. This review provides an updated overview of KADs with a particular focus on KICS in SOT, highlights knowledge gaps for future research, and summarizes recent advances in the screening and management of HHV-8/KSHV infection following transplantation.

Background: A 4-month course of rifampin is one of the recommended first-line regimens for latent tuberculosis infection (LTBI). However, data on its use among kidney transplant candidates (KTC) remain limited.

Methods: We conducted a retrospective study of all KTC treated with either 4-month rifampin or 9-month isoniazid (INH) for LTBI at a transplant infectious disease clinic in Miami from January 1, 2021 to December 31, 2024. We assessed rates of treatment completion, adverse reactions leading to discontinuation of therapy, and transaminase elevation (> 2 times the upper limit of normal). The potential impact of rifampin on blood pressure (BP) in patients on antihypertensive drugs (AHD) known to interact with rifampin was also evaluated.

Results: A total of 66 patients were analyzed (49 [74%] in the INH group and 17 [26%] in the rifampin group). There was a trend towards higher treatment completion in the rifampin group compared to the INH group (16 [94%] vs. 34 [69%], p = 0.05). There was no difference in adverse reactions leading to treatment discontinuation. Transaminase elevations were not observed in the rifampin group, whereas they occurred in 3 (6%) of the INH group. Three patients experienced an increase in BP while receiving rifampin, leading to treatment discontinuation in one case.

Conclusion: A 4-month rifampin course is an excellent option for LTBI among KTC due to its high completion rate and favorable liver safety profile; however, close monitoring for AHD interactions is essential.

Introduction: Studies evaluating the incidence of infections after belatacept as a substitute for calcineurin inhibitors (CNI) or antimetabolite in kidney transplant (KT) yielded conflicting results. We compared infectious outcomes after belatacept-use to no belatacept-use in KT recipients.

Methods: We included patients with primary KT between January 1, 2018, and December 31, 2022. We compared outcomes between those who received belatacept and those who did not. Cox proportional hazards models were used with belatacept as a time-varying covariate and adjusted for gender, age at transplant, donor type, underlying disease, CMV serostatus, and organ transplant type. Anderson-Gill hazard of the first Cox models was used to examine the recurrence of DNAemia.

Results: Of 401 KT recipients, 25 received belatacept. Belatacept-use had a higher hazard for EBV and CMV first infection (3.71 [95% CI 1.57, 8.72; p = 0.003] and 2.63 [95% CI 1.04, 6.70; p = 0.042], respectively), and for allograft failure (14.5 [95% CI 5.15, 41.0; p < 0.001]) and acute cellular rejection (5.08 [95% CI 2.56, 11.5; p < 0.001]). Each year increase in zage had a higher hazard for first EBV (3.71 [1.01, 1.05]; p = 0.005) and CMV infection (1.02 [1.00, 1.04]; p = 0.019). D+/R- CMV serostatus had a higher hazard for first CMV infection relative to other serostatuses (4.96 [3.14, 7.85]; p < 0.001).

Conclusion: Careful selection of KT for belatacept-use is recommended in older recipients (≥ 55 years) due to the increased hazard of mortality, CMV, and EBV DNAemia.

Background: Parvovirus B19 (PVB19) is a clinically important cause of refractory anemia in kidney transplant recipients (KTRs). Data from low- and middle-income settings remain scarce despite high transplant volumes. This study evaluated the clinical spectrum, management practices, and outcomes of PVB19 infection across major transplant programs in India.

Methods: We conducted a retrospective multicenter cohort study across 14 tertiary transplant centers. All KTRs with PCR-confirmed PVB19 infection and complete clinical data were included. Clinical features, bone marrow findings, immunosuppressive (IS) adjustments, intravenous immunoglobulin (IVIG) use, and patient and graft outcomes were analyzed.

Results: A total of 135 KTRs were identified. Median time to infection was 11 weeks posttransplant. Anemia was universal, not frequently accompanied by leukopenia (17.7%) or thrombocytopenia (14.8%). Bone marrow examinations (n = 34) demonstrated giant proerythroblasts or pure red cell aplasia. IS reduction was implemented in all patients; most commonly, complete MMF withdrawal (61.5%). IVIG was administered to 90% (median cumulative dose 100 g). Overall, 97% achieved hematologic recovery, with a median response time of 20 days. Recurrence occurred in 4.4%. At a median follow-up of 18 months, graft survival was 92.6%; graft loss (n = 10) was primarily due to antibody-mediated rejection, and no deaths were attributable to PVB19.

Conclusions: PVB19 infection represents an important consideration in the differential diagnosis of early posttransplant anemia in KTRs. Timely PCR testing and pragmatic treatment strategies can achieve favorable hematologic and graft outcomes in resource-constrained settings.

Background: Pneumocystis jirovecii pneumonia (PCP) is a significant opportunistic infection in solid organ transplant (SOT) recipients. However, the impact of respiratory coinfections on outcomes in this population remains unclear.

Methods: We retrospectively analyzed 112 SOT recipients diagnosed with PCP from April 2018 to March 2024. Respiratory coinfections were defined as identification of significant pathogens in respiratory specimens within 3 days of PCP diagnosis.

Results: Among 112 SOT recipients with PCP, 50.0% required intensive care unit (ICU) admission, and the 30-day and 90-day mortality rates were 12.5% and 17.9%, respectively. Respiratory coinfections were identified in 46 patients (41.1%), including cytomegalovirus (CMV, 30.4%), bacteria (14.3%), and non-CMV viruses (13.4%). Bacterial coinfection was significantly associated with increased 30-day mortality (adjusted odds ratio [aOR], 5.27; 95% confidence interval [CI], 1.15-26.27; p = 0.03) and 90-day mortality (aOR, 4.84; 95% CI, 1.29-19.35; p = 0.02). CMV coinfection was independently associated with prolonged hospital stay (adjusted ratio, 2.42; 95% CI, 1.67-3.50; p < 0.001), higher ICU admission rates (aOR, 2.95; 95% CI, 1.04-9.03; p = 0.05), and increased need for mechanical ventilation (aOR, 3.01; 95% CI, 1.10-8.83; p = 0.04), but not with mortality. Non-CMV viral coinfection was associated with significantly increased odds of ICU admission (aOR, 19.03; 95% CI, 2.67-254.90; p = 0.01) and mechanical ventilation (aOR, 21.21; 95% CI, 2.96-298.12; p = 0.01), without a significant impact on mortality.

Conclusion: In SOT recipients with PCP, bacterial coinfection was associated with higher mortality, while CMV and non-CMV viral coinfections were mainly associated with morbidity. Respiratory co-pathogens may indicate illness severity; whether pathogen-directed strategies can modify outcomes requires further study.

Background: Prior studies and guidelines emphasize PTLD-risk for Epstein-Barr virus (EBV) mismatched (D+/R-) recipients. However, risk among D-/R- kidney recipients remains poorly defined. We evaluated PTLD-risk by donor-recipient EBV serostatus, including D-/R-, and time-varying impact of PTLD on mortality in kidney transplant recipients.

Methods: This retrospective cohort included deceased donor kidney transplants from the US Scientific Registry of Transplant Recipients (2003-2023). Recipient and donor-recipient EBV serostatus were categorical exposures. Time-to-PTLD was analyzed using Kaplan-Meier methods and adjusted Cox models, stratified into 0-1, 1-2, and 2-3 years to address non-proportional hazards. Secondary outcomes included mortality and all-cause graft failure (ACGF), with PTLD modeled as a time-dependent exposure. Effect modification across key subgroups was evaluated.

Results: Among 309 585 recipients (2.35 million person-years), 3147 PTLD events (1.1%) occurred, largely within the first year. Incidence was highest for D+/R- (3%) and D-/R- (1.8%) (p < 0.001). First-year PTLD-risk was highest for D+/R- (HR 17.8 [95% CI: 10.4, 30.5]) and D-/R- (HR 8.2 [95% CI: 4.2, 15.8]) recipients. PTLD was associated with increased mortality (HR 4.5 [95% CI: 4.3, 4.8]) and ACGF (HR 3.7 [95% CI: 3.5, 3.9]), with relatively higher mortality-risk for pediatric recipients (ratio of HRs 1.5). Among 82 detailed PTLD cases, most were B-cell (89%), monoclonal (63%), and EBV-positive (78%), with mixed WHO class and site-involvement.

Conclusions: EBV D+/R- recipients experienced highest and sustained 3-year PTLD-risk, while D-/R- recipients faced previously under-recognized early risk. PTLD was strongly linked to mortality and ACGF, refining counselling and supporting targeted surveillance for high-risk groups.