Transplant Infectious Disease最新文献

Background: Transplant infectious disease (TID) training is not accredited by the Accreditation Council for Graduate Medical Education (ACGME) and is not standardized. Prior surveys of the training landscape in TID have focused on fellow responses; we sought description of programs from program directors and coordinators.

Methods: Along with the American Society of Transplantation (AST) Infectious Disease Community of Practice (IDCOP), we administered a survey to adult and pediatric ID training programs focusing on the structure, funding, curriculum, and outcomes of ID fellows participating in TID fellowships and tracks. This manuscript is a work product of the American Society of Transplantation's Education Committee.

Results: We had 42 respondents representing 15 adult TID fellowships, 12 adult TID tracks, 4 pediatric TID fellowships, and 6 pediatric TID tracks. Adult TID fellowships required slightly more inpatient weeks than adult TID tracks: 26 versus 24 (p = 0.03). A majority of adult TID fellowships 10/14 (71%) rely on multiple sources of funding for their programs. A total of 67% of adult and 75% of pediatric TID fellowships have didactic curriculum, distinct from their general fellowship, and 53% of adult TID fellowships and no pediatric TID fellowships have distinct core competencies to evaluate TID fellows. Most TID fellows are pursuing TID-focused clinical careers.

Conclusions: Substantial heterogeneity exists among TID fellowships, and between fellowships and tracks. Future directions include updating prior guidance for adult and pediatric TID tracks and fellowships on curriculum, core competencies, and baseline requirements to ensure adequate competency in the care of these vulnerable patients.

Background: HHV-6 encephalitis is a serious complication after allogeneic hematopoietic stem cell transplantation. Whether foscarnet prophylaxis improves outcomes after unrelated cord blood transplantation (UCBT), particularly under systemic steroid exposure, and the renal safety of foscarnet remain uncertain.

Methods: This retrospective cohort consisted of 156 adult patients who received single-unit UCBT between 2005 and 2022. Foscarnet prophylaxis was defined as any use of foscarnet without encephalitis onset, including planned administration after transplantation, pre-emptive administration after HHV-6 DNAemia, or other indications. Primary endpoint was 60-day incidence of HHV-6 encephalitis, and secondary endpoints were overall survival and renal function up to 12 months.

Results: The 60-day cumulative incidence of HHV-6 encephalitis was 10.9%; 121/156 (77.6%) received prophylaxis. Incidence did not differ significantly by foscarnet exposure (9.9% vs. 14.3%; p = 0.418) and this was not significant in the multivariable analysis. A high cumulative dose of corticosteroid was associated with higher incidence (28.6% vs. 7.1%; p = 0.001). In patients with low corticosteroid exposure, the incidence of HHV-6 encephalitis was significantly lower with foscarnet prophylaxis (4.3% vs. 14.7%; p = 0.040). Among patients who developed encephalitis, 1-year overall survival appeared higher with prior foscarnet exposure than in those without prior exposure (72.2% vs. 20%); renal function up to 12 months was similar.

Conclusions: Foscarnet prophylaxis was not significantly associated with a reduced incidence of HHV-6 encephalitis after UCBT, whereas high-dose steroid exposure was a risk factor. Notably, a lower incidence of encephalitis with foscarnet prophylaxis was observed in the low-dose steroid subgroup, although this finding requires confirmation in larger cohorts.

The transplant environment requires special considerations when testing for viral infections as immunosuppression results in atypical infection profiles. Microbes otherwise considered commensals or causing mild disease can lead to severe infections in transplant environments. Therefore, guidelines tend to recommend broader microbial testing in these populations. In parallel, advances in molecular diagnostics have led to the availability of a wide selection of tests, including highly multiplexed nucleic acid amplification tests (NAATs) and direct next generation sequencing (NGS) based options. These newer technologies may provide information on many potential pathogens simultaneously, more rapidly, and while avoiding invasive specimen collection procedures. However, they are generally more expensive than conventional methods such as culture, and nucleic acid detection of multiple potential pathogens may be nonspecific and confuse the diagnosis. Navigating the complexity of the available molecular test landscape in immunocompromised patients is an opportunity for diagnostic stewardship. Here we discuss the clinical value of different molecular testing strategies for diagnosis of viral infectious diseases in immunocompromised transplant patients using several common transplant infection syndromes as a framework.

Candida auris is a multidrug-resistant yeast that poses a disproportionate threat to transplant recipients because of prolonged hospitalizations, intensive immunosuppression, frequent invasive procedures, and exposure to broad-spectrum antimicrobials. Despite growing recognition of its propensity for skin colonization, environmental persistence, and biofilm formation on healthcare devices, standardized screening practices for transplant donors and recipients remain poorly defined. Herein, we review published outbreak reports, surveillance studies, laboratory guidance, and public health recommendations to synthesize current approaches to C. auris screening relevant to transplant populations. Key domains included risk-based criteria for admission and response screening, diagnostic modalities (culture, chromogenic media, MALDI-TOF, and real-time PCR), and the applicability of ICU-derived data to transplant settings. Screening strategies include targeted admission or outbreak-driven response. Culture-based methods remain widely used but are slower and require confirmatory testing, whereas molecular assays enable rapid detection with high sensitivity and specificity and permit timely infection-control responses. Much of the data is extrapolated due to a paucity of transplant-specific evidence; available reports suggest frequent colonization in critically ill transplant recipients and high mortality among those who develop invasive disease. No validated decolonization protocols exist, and perioperative screening is not addressed in most guidelines, creating a gap in peri-transplant risk mitigation. Prospective, transplant-focused studies are needed to define optimal perioperative screening, quantify progression risk from colonization to invasive infection, and evaluate the clinical impact of screening on patient outcomes.

Molecular respiratory pathogen panels are an innovative tool for the rapid detection of respiratory pathogens and antimicrobial resistance genes, offering the potential to improve diagnostic accuracy and guide timely antimicrobial therapy. In lung transplantation, their application is especially appealing due to the high incidence of respiratory tract infections and the frequent involvement of multidrug-resistant organisms. This review summarizes the published experiences with molecular respiratory pathogen panels in lung transplant recipients. Current evidence has shown that these panels deliver results faster than conventional microbiology and can support clinical decision-making by confirming or excluding infections. Importantly, these tools cannot replace traditional diagnostics, which remain essential for pathogen susceptibility profiling and identifying organisms not included in the panels. An emerging application involves modulating perioperative antibiotic prophylaxis, where molecular panels may allow earlier adjustment of regimens to address potential donor-derived pathogens. Implemented within structured workflows, molecular panels could help reduce unnecessary antimicrobial exposure and the associated ecological impact. However, limitations still exist, including their inability to detect fungi or less common bacterial pathogens and the risk of over-interpreting colonizing flora. Defined protocols and diagnostic stewardship principles should therefore guide the integration of molecular panels into transplant practice. Further studies are needed to evaluate their cost-effectiveness and to identify patient subgroups who may benefit most from their use.

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: 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.