Transplant Infectious Disease最新文献

Background: Cytomegalovirus (CMV) infection remains among the leading complications after solid organ transplantation (SOT). Large international surveys mainly focused on high-income countries, detected considerable variability in the management of this infection after SOT. Limited data are available from resource-limited settings.

Methods: A questionnaire-based cross-sectional study was performed. All transplant programs (TP) registered at the Brazilian Organ Transplantation Society (ABTO) were invited to participate.

Results: Sixty-one TP participated in the study. Of these, 59 (97%) reported using at least 1 preventive strategy (prophylaxis or preemptive therapy [PET]). Prophylaxis was reported by only 39 (64%). PET was used by 52 (85%), predominantly for R+ recipients (n = 42/61; 70%). CMV monitoring was performed weekly in only 22 of 52 (42%) TP. This was significantly more common in TP reporting turnaround times ≤72 h for quantitative nuclear acid amplification tests (p < 0.001). Intravenous (IV) ganciclovir was the predominant drug chosen for prophylaxis (21/39 TP; 54%) and for PET (44/52 TP; 77%). Lack of regular access to valganciclovir was significantly associated with the choice of IV ganciclovir for prophylaxis and PET (p = 0.002 for both comparisons). Only 8 (13%) TP had access to molecular diagnostic tests for ganciclovir resistance, and 14 (23%) had access to effective therapy for highly resistant infections.

Conclusion: These results suggest that strategies to improve the management of CMV after SOT in such a resource-limited setting are needed and should include not only targeted educational programs but also initiatives to tackle economic and structural barriers.

Background: Multiple outpatient therapies have been developed for COVID-19 in high-risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population.

Methods: We performed a retrospective cohort study using de-identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID-19 between January 2022 and December 2023, and underwent SOT prior to COVID-19. The primary outcome was 30-day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables.

Results: 4192 SOT recipients with COVID-19 were identified. 1403 received an outpatient COVID-19 therapy, including anti-spike monoclonal antibodies (N = 748, 53.3%), molnupiravir (N = 327, 23.3%), ritonavir-boosted nirmatrelvir (N = 217, 15.5%), or remdesivir (N = 141, 10.0%). In weighted analysis compared to no treatment, anti-spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28-0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36-0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25-0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50-1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti-spike monoclonal antibodies.

Conclusions: Outpatient COVID-19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30-day hospitalization, except for remdesivir. The choice of outpatient COVID-19 therapy in SOT recipients should primarily account for patients' individual circumstances and drug-drug interactions rather than differential therapeutic efficacy.

Background: Kidney transplant (KT) recipients at intermediate risk for cytomegalovirus (CMV) infection constitute a potential target for individualized prevention strategies informed by the CMV-specific cell-mediated immunity (CMV-CMI). The optimal method for the functional assessment of CMV-CMI in this group remains unclear.

Methods: We included 74 CMV-seropositive KT recipients that did not receive T-cell-depleting induction and were managed by preemptive therapy. CMV-CMI was monitored at baseline and months 1, 3, 6, and 12 by intracellular cytokine staining (ICS) and a interferon (IFN)-γ-release assay (QuantiFERON-CMV [QTF-CMV]). Both methods were compared for discriminative capacity (areas under the receiving operating characteristic curve [auROCs]) and diagnostic accuracy to predict protection against high-level (≥1000 IU/mL) CMV DNAemia and/or disease.

Results: Eighteen patients (24.3%) experienced high-level CMV DNAemia or disease. There were no significant differences in the discriminative capacity to predict protection of CMV-specific CD8+ (auROC: 0.719) and CD4+ T-cell counts (auROC: 0.664) enumerated by ICS and IFN-γ production measured by QTF-CMV (auROC: 0.666). Optimal cutoff values of ≥9.8 CMV-specific CD4+ T-cells/µL and ≥5.7 CD8+ T-cells/µL by ICS yielded excellent specificity (95.7% and 86.9%, respectively) and positive predictive values (PPVs) (>98.0%), but a sensitivity below 60%. A reactive QTF-CMV (IFN-γ ≥0.2 IU/mL) provided good sensitivity (81.6%) and PPV (92.5%), at the expense of a poor specificity (22.2%).

Conclusions: The discriminative capacity to predict immune protection against clinically relevant CMV infection among intermediate-risk KT recipients was comparable for ICS and QTF-CMV. A selected ICS threshold may provide better specificity than the interpretative cut-off values currently recommended for QTF-CMV.

Background: Patients with cancer are at elevated risk for tuberculosis (TB) reactivation. Diagnosis of latent TB infection and TB disease remains challenging in this patient population despite the advent of interferon-γ release assays (IGRA).

Methods: We retrospectively reviewed medical records of all patients with cancer who had IGRA testing (QuantiFERON-TB [QFT-TB] or T-SPOT.TB) at a major cancer center in the United States from June 2010 to July 2017. The results were analyzed with respect to the likelihood of latent TB infection and TB disease.

Results: A total of 1299 patients were included with 1599 tests performed: 586 QFT-TB and 1013 T-SPOT.TB. Forty-nine (4%) patients were diagnosed with latent TB, and four (1%) with TB disease. T-SPOT.TB was more likely to yield an actionable result (positive or negative) than QFT-TB (89% vs. 65%, p < 0.001). The rate of indeterminate results for QFT-TB was higher than the rate of invalid results for T-SPOT.TB (35% and 10%, respectively, p < 0.001). On multivariate analysis, independent predictors of an invalid T-SPOT.TB included prior receipt of alemtuzumab, lower hemoglobin, absolute lymphocyte count, or serum albumin (p < 0.05 each), whereas the independent predictors of an indeterminate QFT-TB were female gender, prior receipt of systemic corticosteroids, and lower hemoglobin, or serum albumin or higher absolute neutrophil count (p < 0.05 each).

Conclusions: T-SPOT.TB yielded more actionable results than QFT-TB in patients with cancer. T-SPOT.TB might be a better IGRA for screening for latent TB infection in patients with cancer, although a direct comparison would be needed to definitively determine this.

This case involves a 52-year-old male, who underwent a deceased donor orthotopic liver transplant 7 months prior, presented with a 2-week history of persistent fever, anemia, thrombocytopenia, and mild elevation of liver enzymes. Upon hospital admission, the patient was febbrile, alert and oriented, hemodynamically stable. Laboratory exams revealed worsening leukopenia, anemia, thrombocytopenia, hyponatremia, and elevated ferritin. On hospital day 5, the general condition of the patient rapidly deteriorated with dyspnea, asthenia, and worsening fever and pancytopenia.Computed tomography revealed splenomegaly and minimal bilateral pleural effusion.

Introduction: With reports of expanding epidemiology of blastomycosis across the United States, the purpose of this study was to evaluate the incidence and outcomes associated with blastomycosis in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients.

Methods: We conducted a retrospective case series of adult SOT and HCT recipients at a tertiary care medical center between January 1, 2005 and September 30, 2023. Cases were defined as culture-proven blastomycosis. We performed descriptive statistical analysis to evaluate diagnosis, management, and outcomes (mortality) of blastomycosis in SOT.

Results: The cumulative incidence of blastomycosis was 0.11% with a median time to infection following transplant of 743 days. Of the 19 cases, the majority of patients were SOT recipients (90%). Supratherapeutic immunosuppression within 30 days of diagnosis was observed in 42% of cases with documented drug monitoring. Urine antigen testing was highly sensitive (100%). Fourteen (73.7%) patients received induction therapy with liposomal amphotericin B followed by azole therapy for a minimum of 12 months. Despite appropriate treatment, 1-year mortality was high at 26.3%, with attributable mortality of 21.1%.

Conclusions: While rates of blastomycosis remain low among SOT and HCT recipients, infection is associated with poor posttransplant outcomes. Antigen testing can aid in timely assessment of disease severity and initiation of appropriate therapy. Among survivors, no relapses were observed while on lifelong secondary suppression. Future studies should aim to better define risk factors associated with developing blastomycosis and establish effective strategies for prevention.

Background: Identifying patients with latent tuberculosis infection (LTBI) is challenging. This is particularly true amongst immunocompromised hosts, in whom the diagnostic accuracy of available tests is limited. The authors evaluated the impact of routine pretransplant review by a transplant infectious diseases (TID) physician on LTBI screening in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients.

Methods: Adult patients who received an alloHSCT between January 2018 and December 2022 were eligible for inclusion. Data were retrospectively extracted from patient records. Participants were dichotomized into those that had a routine pretransplant review with a TID physician and who that did not.

Results: Of the 116 participants included, 61.2% had a documented TID review. This intervention was associated with more frequent initiation of LTBI treatment (8.5% vs. 0.0%) and a tendency for LTBI treatment to be initiated in the absence of immunodiagnostic criteria (7.1% vs. 0.0%). A case of LTBI reactivation occurred in each group.

Conclusion: Routine pretransplant review by TID physicians improved the recognition of risk factors for LTBI and increased the initiation of LTBI treatment in patients with a high pretest probability of LTBI. Further research is needed to evaluate the utility of routine pretransplant TID review and to determine the optimal strategy for preventing LTBI reactivation amongst alloHSCT recipients in low-endemic settings.