Transplant Infectious Disease最新文献

Background: Valganciclovir (VGCV) prophylaxis effectively prevents cytomegalovirus infection in lung transplant patients. However, VGCV-induced neutropenia causes early cessation. Nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 degrades the ganciclovir (GCV) triphosphate, an active metabolite. We assessed the effects of NUDT15 variants on neutropenia and VGCV cessation in recipients of lung transplants.

Methods: We recruited 28 patients who had received lung transplants and VGCV prophylaxis and genotyped NUDT15 exons 1-3 using Sanger sequencing. Neutrophil counts were monitored from 1 month to 1 year in the wild-type and NUDT15 reduced-function variant groups. Cumulative incidences of neutropenia (< 1500/mm³) and neutropenia-related cessation within 1 year, including late-onset neutropenia, were assessed using Kaplan-Meier analysis. A subgroup analysis was conducted focusing on patients with stable renal function, the primary route of excretion for GCV.

Results: Of the 28 patients, nine carried NUDT15 variants (Arg139Cys, Val18Ile, Val18_Val19insGlyVal, Arg139Cys/Val18Ile). The neutrophil count nadir within 1 month of treatment was lower in the NUDT15-variant group than in the wild-type group. A higher incidence of neutropenia and VGCV cessation was observed in the NUDT15-variant group, but without statistical significance. Among 13 patients with stable renal function, all four in the NUDT15-variant group developed neutropenia and cessation within 60 days, compared with two of nine in the wild-type group. Covariance analysis showed that NUDT15 variants were associated with decreased neutrophil counts, independent of GCV trough concentration.

Conclusion: NUDT15 variants increase the risk of early neutropenia during VGCV prophylaxis in lung transplant recipients.

Introduction: Limited data exist regarding the burden of intensive care unit (ICU)-acquired infections in the early post-solid organ transplant (SOT) period, particularly in multidrug resistant organisms-endemic settings. This study aims at describing the epidemiology, clinical characteristics, and outcomes of patients who developed an ICU-acquired infection following a SOT procedure in Italy from 2018 to 2024.

Methods: A multicenter, retrospective study was conducted within the Italian PROSAFE project across 31 ICUs from 2018 to 2024. All adult patients admitted to ICU during the same hospitalization as their organ transplant procedure were included. Bloodstream infections, ventilator associated pneumonia, intra-abdominal infections, and urinary tract infections occurring more than 48 h after ICU admission were retrieved.

Results: Among 2210 SOT recipients, 154 (6.9%) developed 193 ICU-acquired infections. Ventilator associated pneumonia was the most frequent (74, 38.3%), followed by bloodstream infections (56, 29%). Multidrug resistant organisms were identified in 34/87 (39%) isolates with available antibiogram. ICU-acquired infections were associated with significantly higher intra-ICU mortality (35/154, 22.4% vs. 49/2056, 2.4%; p < 0.001) and longer ICU stays (24 vs. 4 days; p < 0.001). Patients with infections due to multidrug resistant organisms showed higher mortality and length of stay.

Conclusions: ICU-acquired infections occurred in nearly 7% of SOT recipients admitted to ICU following a SOT procedure, with a significant contribute of multidrug resistant organisms. These infections were associated with striking differences in mortality and length of stay. Finally, this study suggested that patients with MDRO infections showed trends toward higher mortality and length of stay.

Background: Respiratory viral infections (RVIs) significantly impact patients with hematologic malignancies (HMs). During the 2023-2024 respiratory viral (RV) season, we observed a decline in SARS-CoV-2-related hospitalizations in our center compared to the two previous seasons. Given the changing epidemiology of RVIs in the post-pandemic era, the low acceptance of SARS-CoV-2 and influenza vaccination, and the availability of new respiratory syncytial virus (RSV) vaccines in 2023, we aimed to compare outcomes of RSV, influenza, and SARS-CoV-2 infections in patients with HMs during the 2023-2024 RV season.

Methods: We retrospectively analyzed adults with HMs diagnosed with RSV, influenza, or SARS-CoV-2 between October 2023 and April 2024. The primary outcomes were lower respiratory tract infection (LRI), hospitalization, and 30-day all-cause mortality.

Results: We identified 503 patients with 536 consecutive RVIs: 50.0% with SARS-CoV-2, 26.1% with RSV, and 22.2% with influenza (1.7% co-infections). Among RSV-infected patients, 50.7% developed LRI, compared to 41.2% with influenza and 39.2% with SARS-CoV-2 (p = 0.076). The 30-day all-cause mortality was 9.3% for RSV, 7.6% for influenza, and 3.4% for SARS-CoV-2 (p = 0.037). In the multivariable analysis, RSV was associated with higher LRI rate compared to SARS-CoV-2, along with older age, refractory/relapsed cancer, nosocomial infections, and lymphopenia. Older age, allogeneic hematopoietic cell transplantation, nosocomial infections, and LRIs were associated with increased mortality.

Conclusions: During the 2023-2024 RV season, the clinical impact of these viruses on patients with HMs remains significant, with higher morbidity and mortality from RSV, highlighting the persistent unmet need for better management strategies for RVIs in the post-pandemic era.

Background: Limited data exists on the incidence of CMV infections after chimeric antigen receptor (CAR) T-cell or bispecific antibody (BsAb) therapy for hematologic malignancies.

Methods: We reviewed medical records of patients with hematologic malignancies treated with CAR T-cells or BsAbs between July 2018 and October 2024 in a tertiary hospital in Seoul, South Korea. CMV infections were detected using CMV DNA qPCR assays performed within 180 days after CAR T-cell infusion or the last BsAb treatment. Secondary outcomes were the occurrence of clinically significant CMV infections (CS-CMVi) and end-organ diseases.

Results: Of 179 patients, 76 (42%) received CAR T-cell therapy, and 103 (58%) received BsAb therapy. The incidence of CMV infection was 62% in BsAb recipients, and 43% in CAR T-cell recipients. Two (6.1% of total CMV infections) CAR T-cell recipients had CS-CMVi, and 1 (3.0%) developed possible CMV pneumonia. In the BsAb group, 10 (16% of total CMV infections) patients received antiviral therapy, and 4 (6.3%) had end-organ diseases. Receiving three or more previous systemic chemotherapy regimens in the CAR T-cell group was associated with increased CMV infection risks (HR 4.7, 95% CI 1.88-11.8, p < 0.001), and older age in the BsAb group had a trend toward having more CMV infection (HR 1.02, 95% CI 1.00-1.05, p = 0.06).

Conclusion: Approximately 43% and 62% of patients receiving CAR T-cell and BsAb therapy had CMV infection, with 1%-4% developing CMV diseases. Effective strategies for preventing CMV infections in these patients are warranted.

This case describes a 62-year-old male who underwent kidney transplantation and was admitted 8 weeks post-operatively for evaluation and management of abdominal pain, nausea, and diarrhea. An extensive workup was performed, ultimately leading to a diagnosis of Strongyloides hyperinfection syndrome. This case highlights the importance of awareness of strongyloidiasis in non-endemic regions, management of Strongyloides hyperinfection syndrome in the post-transplant setting, and strategies for donor and recipient screening.

Background: Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (HSCT) leads to significant morbidity and mortality. Recently, a pivotal trial demonstrated extended duration of letermovir until post-HSCT Day 200 reduced clinically significant CMV infection (csCMVi). Here we evaluated the real-world efficacy of extended letermovir.

Methods: We retrospectively reviewed consecutive patients who underwent HSCT and received letermovir prophylaxis for CMV seropositivity of the donor and/or the recipient at a transplant center between July 2018 and March 2024.

Results: A total of 236 HSCTs with letermovir prophylaxis were performed. Letermovir was administered until Days 75-125 in 189 cases, and until Day 150- in 37 cases, who were assigned as short and extended letermovir group, respectively. The cumulative incidence of csCMVi at Day 200 was significantly lower in cases with extended letermovir, with no patient developed csCMVi in this group compared to 26.8% in short prophylaxis group (p < 0.001). However, the incidence was comparable at Day 400, with 19.7% in extended and 28.4% in short prophylaxis group (p = 0.14). Multivariable analysis for csCMVi showed age ≥ 50 years at HSCT (hazard ratio [HR], 3.24; p < 0.001) and steroid administration at letermovir discontinuation (HR, 2.25; p = 0.003) were identified as significant risk factors, and patients with both factors were associated with higher incidence of csCMVi regardless of letermovir duration. Immunoglobulin G, but not lymphocyte count, was persistently lower in these high-risk patients until Day 400.

Conclusion: Despite the efficacy of letermovir in preventing csCMVi during immunosuppression, the occurrence of csCMVi following letermovir cessation was still a clinical concern.

Background: Allogeneic hemopoietic stem cell transplant (aHSCT) recipients are at high-risk for invasive fungal disease (IFD), even with mould-active antifungal prophylaxis (AFP).

Methods: This was a retrospective, observational, single-center cohort study involving 300 adult aHSCT recipients transplanted from January 2017-May 2020. Patient demographics, underlying hematological malignancy (HM), transplant characteristics and AFP were described. The primary objectives were rate and characteristics of breakthrough IFD (bIFD) within 1-year post-transplant.

Results: Of 300 aHSCT recipients, 195 (65%) were males; median age at transplantation was 54 years (IQR 43-62). Acute leukemia was the most common underlying HM (50%), and modified-release posaconazole was the main primary AFP (88%). B-IFD occurred in 26 patients (9%): 14 breakthrough invasive mould diseases (bIMD), which Aspergillus species predominated (56%), followed by Lomentospora prolificans (31%); and 12 breakthrough invasive yeast infections, with Nakaseomyces glabratus most frequently isolated. Neither Aspergillus fumigatus complex nor Candida albicans was cultured as breakthrough organisms. bIMD occurred late post aHSCT at median of 167 days, whereas breakthrough invasive yeast infection occurred at median of 21 days. Twelve patients (46%) had therapeutic-drug-monitoring at time of bIFD-all were within therapeutic range. All-cause mortality at 12-weeks from bIMD and breakthrough invasive yeast infection infections were 50% and 58%, respectively.

Conclusion: Although bIFD rate was consistent with other reports, mortality after bIFD remained significant. Use of mould-active AFP likely explained the changing epidemiology of fungal isolates. Resistant breakthrough fungal organisms, especially L. prolificans, reflected local epidemiology. Ongoing surveillance of IFD including resistant organisms is warranted to optimize treatment and patient outcome.

Background: Data on disseminated herpes zoster (HZ) infections in solid organ transplant (SOT) recipients are limited. We aimed to investigate the clinical characteristics and outcomes of HZ infection in SOT patients presenting with microbiologically confirmed disease.

Methods: All SOT recipients who tested positive for varicella-zoster virus (VZV) from any sample type between January 2013 and December 2022 were included. Disseminated HZ was defined as skin lesions involving > 2 contiguous dermatomes or evidence of end organ disease. An analysis of risk factors associated with disseminated infection was performed.

Results: A total of 146 adult SOT patients with confirmed VZV infections were included in the study. Of these, 4 were primary varicella and 142 were HZ. Median time to HZ presentation was 1.8 years (range 0.02-27). Disseminated HZ was diagnosed in 55/142(38.7%). Post-herpetic neuralgia (PHN) occurred in 33(22.6%) patients and vaccine breakthrough in 5(3.5%). Hospitalization was in 101(71.6%) patients, and 5(3.5%) died within 30 days, none attributable to HZ. VZV DNAemia was detected in 12/13 (92.3%) patients with disseminated disease versus 11/29 (37.9%) with localized disease (p = 0.002). Recurrent HZ rate was 10/142 (7.0%) over a median follow-up of 4.1 years with 90% of recurrences occurring in thoracic transplant. On multivariable logistic regression, no clinical factors were associated with disseminated disease.

Conclusions: In a large cohort of SOT patients with VZV, disseminated disease and PHN were frequent. VZV DNAemia was noted in both disseminated and localized infections suggesting that subclinical detection of virus in blood is frequent. The implications of this require further study.