Transplant Infectious Disease最新文献

Background: Liver transplant (LT) recipients are vulnerable to COVID-19 due to immunosuppression and comorbidities. This study evaluated the association between social determinants of health (SDOH) and COVID-19-related mortality (C19M) in LT recipients in the United States.

Methods: We utilized the Scientific Registry of Transplant Recipients to collect information on adult LT recipients between March 13, 2010 and December 31, 2023. We evaluated the incidence and risk factors for C19M among primary LT recipients using univariable and multivariable competing risk analysis.

Results: There were 82 995 prevalent LT recipients with 7817 non-C19 deaths and 671 C19M. Non-medical factors associated with higher C19M included Hispanic ethnicity (subdistribution hazard ratio [SHR] = 1.72; 95% CI = 1.31-2.26; ref = White), Native American/American Indian race (SHR  =  3.59; 95% CI  =  2.29-5.64; ref = White), Medicare insurance (SHR  =  1.40; 95% CI = 1.16-1.69; ref = private insurance), less than high school-level education (SHR  =  1.35; 95% CI  =  1.14-1.59; ref = > high school-level education), and residency in highly distressed communities (highest Distressed Community Index (DCI); SHR = 1.33; 95% CI  =  1.01-1.75; ref = lowest DCI). Medical factors associated with higher C19M included higher BMI, diabetes, MELD score, and simultaneous liver and kidney transplants.

Conclusion: SDOH are significantly associated with C19M in LT recipients. While focused on the United States, these findings have international relevance, emphasizing the importance of integrating SDOH into transplant risk assessment and targeted public health interventions. Addressing social and geographic disparities is critical for protecting immunocompromised transplant populations during the pandemic and other infectious-related emergencies.

Introduction: In allogeneic HCT recipients, risk factors for PTLD and EBV end-organ diseases are well established. Therefore, weekly monitoring of EBV reactivation with quantitative PCR is indicated for patients at risk. Although based on uncontrolled studies and supported by moderate strength of evidence, preemptive rituximab has been recommended in cases of EBV reactivation, without a clearly defined EBV DNAemia threshold. Rituximab is known to be associated with prolonged B-cell depletion and secondary hypogammaglobulinemia, resulting in an increased risk of infectious complications and poor vaccine responses for an extended period.

Methods: In this retrospective single-center study, we evaluated the safety and effectiveness of immunosuppression (IS) reduction as the first approach in EBV reactivation in 328 HCT recipients, limiting the introduction of rituximab to patients who did not respond to IS reduction or who developed EBV end-organ disease or PTLD.

Results: During follow-up, 178 patients experienced EBV reactivation, with a cumulative incidence of 54.6%. Among these, four patients developed EBV encephalitis (2.2%), and no cases of PTLD were identified. Rituximab was administered to only 12 patients (6.7%). In multivariate analysis, EBV reactivation was significantly associated with chronic GVHD, which may be related to EBV reactivation itself, rapid IS withdrawal, or both. EBV reactivation did not adversely affect non-relapse mortality or overall survival in this cohort.

Conclusion: IS reduction as the first-line approach to EBV reactivation was safe and effective in most patients with increasing EBV DNAemia. Consequently, rituximab was required in fewer than 10% of cases.

Background: Malaria during hematopoietic stem cell transplant (HCT) poses serious risks. Historically, donors with potential exposure were deferred or treated empirically. Malaria PCR, the most sensitive diagnostic tool, is not routinely used. Patients with sickle cell disease (SCD) and their related donors may be disproportionately affected given endemic exposures and potential occult parasitemia.

Methods: Performed a single-center retrospective review of malaria screening and outcomes in patients with SCD undergoing allogeneic HCT and their related donors. In addition, reviewed the literature on HCT-related malaria cases.

Results: Among 57 HCT donors tested for malaria, three asymptomatic cases were identified. Two were identified prior to donation via blood smears and PCRs, while one-initially screened with smears alone-was diagnosed retrospectively after transmitting malaria to the recipient. Retrospective malaria PCR of the hematopoietic cell product was positive, suggesting the donor's pre-collection whole-blood malaria PCR may have been positive. Among 52 HCT recipients tested for malaria, two developed peri-HCT malaria-one diagnosed and treated pre-HCT, and another with donor-derived malaria. All cases diagnosed before collection and HCT proceeded successfully after treatment and negative PCR. Literature review identified 10 detailed malaria cases in HCT and two additional series lacking case specifics.

Discussion: Asymptomatic HCT donors and candidates with potential exposure to malaria should undergo screening. Malaria PCR offers greater diagnostic sensitivity than conventional methods. PCR utilization may prevent unnecessary donor deferrals and avoided empiric malaria treatment. Moreover, PCR negativity post-treatment may help confirm donor and candidate eligibility. These observations warrant validation in larger studies.

Background: Respiratory viral infections (RVIs) can have distinct clinical presentations and outcomes in non-lung solid organ transplant (SOT) recipients compared to non-transplant and lung transplant patients. Understanding their impact is crucial for improving patient care and outcomes.

Methods: This multicenter retrospective study analyzed adult non-lung SOT recipients with PCR-confirmed symptomatic RVIs from eight Dutch hospitals (January 2013-July 2024) to characterize clinical characteristics and outcomes of mono- and co-infections and identify risk factors for intensive care admission or 30-day mortality.

Results: In total, 603 RVIs were identified in 460 recipients (kidney: 501; liver: 75; pancreas/islet of Langerhans: 4; combined: 23). The most common viruses were SARS-CoV-2 (36%), influenza A/B (29%), rhinovirus (14%), and RSV (7%). Influenza cases showed higher rates of fever (72%), common cold symptoms (37%), and myalgia (29%) than other viruses. Hospitalization occurred in 68% (384/565). Factors independently associated with intensive care admission or 30-day mortality included higher CURB-65 score (OR 1.91; 95% CI 1.36-2.70; p < 0.01), radiologic infiltrates (OR 3.04; 95% CI 1.60-5.80; p < 0.01), and SARS-CoV-2 infection (OR 1.67; 95% CI 1.05-2.67; p = 0.03). In contrast, influenza infection was associated with a lower risk (OR 0.21; 95% CI 0.07-0.62; p < 0.01). Co-infections were not linked to worse outcomes compared to mono-infections.

Conclusion: Overall, RVIs in non-lung SOT recipients were associated with high hospitalization and mortality rates. SARS-CoV-2 posed the highest risk for complications, while influenza was associated with a lower risk of severe outcomes. No association was found between co-infection and poor outcomes.

Background: Multidrug-resistant organism colonization and infections cause significant morbidity and mortality in solid organ transplantation, affecting the perioperative antibiotic management. Yet, international practices for screening and antibiotic prophylaxis in colonized donors and recipients remain poorly defined.

Methods: Self-administered, web-based survey conducted between February and July 2025 to assess global practices in multidrug-resistant organism screening and perioperative antibiotic management in SOT, developed by transplant infectious diseases experts and endorsed by the Transplant Infectious Diseases Section of the Transplantation Society and the European Society of Clinical Microbiology and Infectious Diseases Study Group for Infections in Compromised Hosts. Data collected included respondent and institution characteristics; screening and prophylaxis protocols; donor and recipient colonization management; and timeframes relevant for prophylaxis modification.

Results: Responses from 125 transplant centers across 24 countries and four continents were included. Most respondents were infectious disease physicians (73.6%). Antimicrobial stewardship programs and transplant infectious diseases consultation were available in 93.6% and 85.6% of centers, respectively. Over half (52.0%) modified prophylaxis based on donor multidrug-resistant organism colonization, mainly triggered by urine and respiratory cultures. Preservation fluid and surveillance cultures influenced decisions less often. Recipient screening protocols were reported by 61.6% of centers, primarily targeting carbapenem-resistant Enterobacterales (80.8%). About 41.6% routinely adjusted prophylaxis for colonized recipients, especially with recent (1-3 months) colonization.

Conclusion: Substantial international variability exists in multidrug-resistant organism screening and perioperative prophylaxis practices in solid organ transplantation. Evidence-based consensus guidelines are needed to standardize and improve prevention of donor-derived and recipient infections globally.

Background: The use of organs from donors at increased infectious risk represents an effort to broaden the donor pool, but case-by-case evaluation may be needed. The Italian National Transplant Center (CNT) is supported by a second opinion task force of experts consulted for donors with complicated infectious assessment.

Methods: Retrospective observational study to describe infectious disease second opinion (IDSO) activity between June 2022 and October 2023. We analyzed the distribution of the infectious risk level, assigned according to the CNT protocol in five categories.

Results: IDSO evaluation was requested for 1246 of the 4153 (30%) of the donors. The mean age was 58.2 years, 56.8% were male, and most of them were Italians (91%). Donors had on average 1.5 (SD 0.9, range 1-6) infectious problems, the most frequent being pneumonia (453, 36.4%), inflammatory marker elevation (299, 24%), and bacteremia (125, 10%). The infectious risk was classified in most cases as increased but acceptable risk (60.8%), followed by negligible risk (19.2%) and increased but acceptable risk only for critical recipients (12.4%). Only 5.2% of donors were unacceptable, the main reason being inappropriately treated multidrug-resistant organism bacteremia or candidemia (21/65, 32.3%). Lung was the most frequently excluded organ (18.2%). In 284 donors (24%), additional testing was recommended, and in 299 recipients (25.3%), a specific therapeutic indication was given.

Conclusions: IDSO activity allowed the acceptance of the donor pool in almost 95% of the reviewed cases. Prospective international studies are necessary to understand the real impact of donors at increased infectious risk on recipient outcomes.

Background: Neutropenia during valganciclovir (VGCV) prophylaxis for cytomegalovirus infection in pediatric solid organ transplant (pSOT) recipients is common, but it is uncertain if this toxicity is exposure-dependent.

Methods: To compare ganciclovir (GCV) exposures in children treated with VGCV with and without neutropenia, we performed a retrospective matched case-control study among pSOT prescribed VGCV, dosed based on body surface area. Cases were defined as an absolute neutrophil count (ANC) < 1000/µL. Controls without neutropenia were matched by age (+/-1 year), transplanted organ, and duration of VGCV prophylaxis. We used a published population pharmacokinetic model to inform predictions of GCV concentrations using Pmetrics, accounting for each subject's time-dependent variables (age, weight, creatinine clearance). We then calculated 24-h, 7-day, and cumulative area under the curve (AUC) in each subject and used conditional logistic regression to compare GCV exposures among cases and controls.

Results: Among 164 pSOT recipients prescribed VGCV, we identified 35 case-control matches. There were no statistically significant differences in the 24-h (odds ratio [OR] 0.990, 95% confidence interval [CI] 0.964-1.018), 7-day (OR 1.000, 95% CI 0.996-1.004), or cumulative AUCs (OR 1.00, 95% CI 0.9996-1.00) among all cases and controls. AUC metrics by SOT type also showed no statistically significant differences.

Conclusions: Predicted GCV exposures were similar among pSOT recipients with and without neutropenia, suggesting that differences in dosing and pharmacokinetics covariates did not drive toxicity in our population. Measurement of GCV concentrations may discern whether toxicity relates to exposures/concentrations or intrinsic factors (i.e., genetics) in the pSOT population.