Transplant Infectious Disease最新文献

Background: Ureaplasma and Mycoplasma species (spp.) infections have been associated with increased morbidity and mortality in lung transplant (LTx) recipients due to their association with hyperammonemia syndrome (HS) and wound dehiscence. This study aims to assess the clinical outcomes in LTx recipients treated with preventative doxycycline.

Methods: We conducted a single-center retrospective review of LTx recipients from January 2020 to February 2024. In November 2023, our center began administering doxycycline prophylaxis (ppx) postoperatively until bronchoalveolar lavage PCR results for Mycoplasma and Ureaplasma spp. were available. Doxycycline was discontinued if the PCR was negative and continued for 14 days if positive.

Results: A total of 98 LTx recipients were reviewed, with 3 excluded due to death before surveillance. Of these, 70 tested negative for Mycoplasma and Ureaplasma spp., 8 were not tested, and among the 17 positives, 11 received doxycycline ppx. The incidence of HS was lower in the ppx group (0% vs. 50%). The ppx group had shorter median duration of mechanical ventilation (MV) (3 vs. 20 days), ICU stay (9 vs. 22 days), and hospital stay (24 vs. 30 days). No significant difference was found in the rates of anastomotic dehiscence (18% vs. 17%).

Conclusions: Doxycycline ppx was associated with a lower incidence of HS, decreased duration of MV, and shorter ICU and hospital length of stay in this cohort of LTx recipients. These findings suggest that doxycycline, an inexpensive and relatively well-tolerated intervention, may prevent HS after LTx.

Invasive fungal diseases (IFD) have been recognized by WHO as of critical significance to human health requiring investment in surveillance, diagnostics, new treatments, and antifungal stewardship which should adopt a one health approach. IFD continue to complicate immunosuppressive therapies such as those for hematological malignancy and allogeneic hematopoietic cell transplantation (alloHCT) with a mortality of 30%-80%. However, new approaches to GVHD prophylaxis and treatment, longer survivorship, expanded access to transplantation, and haploidentical donors are changing the landscape of IFD post alloHCT. As well as expanding risk groups, the geographic reach of certain endemic infections is expanding due to climate change. Alongside these changes requiring clinicians to have heightened awareness of IFD even outside of traditional risk groups and geographic locations, new diagnostics and antifungal therapies are reaching the clinic. This is a timely development as rates of antifungal resistance to first line agents, such as azoles, are increasing and as more high-risk patients receive antifungal prophylaxis, more resistant mold infections are increasingly seen. This review will address the changes in the field of IFD in patients receiving alloHCT and the evolving knowledge on new antifungal treatment options.

Introduction: The objective of this study was to analyze outcomes associated with letermovir for CMV primary prophylaxis in adult CMV-seropositive allo-HCT recipients in a multicenter real-world scenario.

Methods: This retrospective real-world international study involved 481 adults undergoing allo-HCT between 2018 and 2020 who received letermovir for primary prophylaxis. Outcomes included clinically significant CMV infection (csCMVi), graft-versus-host disease, opportunistic infections, all-cause mortality, hospitalizations, and ICU admissions. The median follow-up was 33.8 months.

Results: The median start time of letermovir was 3 days after transplant, with a median duration of prophylaxis of 100 days. The cumulative incidence of csCMVi was 2.7% (95% CI = 1.5-4.5) at 3 months, 13.1% (95% CI = 10.3-16.3) at 6 months, and 17.1% (95% CI = 13.9-20.6) at 12 months. The median time from HCT to csCMVi was 142 days. In multivariate analysis, four factors contributed to development of csCMVi: reduced-intensity conditioning (HR = 1.90; 95% CI = 1.17-3.08; p = 0.009), peripheral blood as cell source (HR = 2.92; 95% CI = 1.00-8.50; p = 0.0495), pretransplant CMV serostatus D-/R+ (HR = 2.24; 95% CI = 1.42-3.53; p = 0.0005), use of alemtuzumab (HR = 3.91; 95% CI = 1.60-9.59; p = 0.003). There was no difference in the cumulative incidence of csCMVi in the first 100 days between patients who started letermovir ≤ 5 versus > 5 days after transplant. Factors adversely contributing to overall survival: age as a continuous variable, 10-year effect (HR = 1.23; 95% CI = 1.08-1.41; p = 0.002), patient male sex (HR = 1.48; 95% CI = 1.02-2.13; p = 0.038), status > CR1 of disease at transplant (HR = 1.97; 95% CI = 1.36-2.85; p = 0.0004), PB as stem cell source (HR = 1.81; 95% CI = 1.04-3.15; p = 0.04), acute leukemia diagnosis (HR = 1.61; 95% CI = 1.10-2.34; p = 0.01), CMV high-risk patients (HR = 1.52; 95% CI = 1.02-2.27; p = 0.04).

Conclusions: An analysis of real-world use of letermovir in CMV prophylaxis after allo-HCT showed a low incidence of csCMVi compared to previously published information.

Background: Urinary tract infections (UTIs) in kidney transplant (KT) recipients are frequent and associated with increased morbidity and mortality. Traditional outcome measures may underestimate its true clinical burden. The Desirability of Outcome Ranking (DOOR), developed by the Antibacterial Resistance Leadership Group, is a patient-centered composite outcome designed to capture the full spectrum of infectious complications.

Methods: We refined the DOOR framework for complicated UTIs by incorporating transplant-specific variables and evaluated its application in a cohort of KT recipients with UTIs between 2013 and 2023.

Results: Ninety-seven patients with carbapenem-resistant (CR) UTIs were matched 1:1 by infection year to patients with carbapenem-susceptible (CS) infections. Compared with the standard cUTI DOOR, the KT-UTI DOOR reclassified 41 patients to worse outcome ranks. Using the KT-UTI DOOR, the probability of a more favorable outcome in CR versus CS infections was 41.3% (95% CI: 34.2%-48.7%, p = 0.02) in the unadjusted analysis and 43.4% (95% CI: 36.2%-50.9%, p = 0.08) after adjustment. Transplant-related complications were the only events independently associated with CR infections. In contrast, using the established cUTI DOOR, the corresponding probability was 45.8% (95% CI: 38.8%-52.9%, p = 0.24) in the adjusted analysis.

Conclusion: Incorporating transplant-related variables improves the clinical relevance of DOOR in KT recipients.

Background: CD19-directed chimeric antigen receptor (CAR) T-cell therapy has exhibited efficacy in treating relapsed/refractory high-grade B-cell malignancies, but off-tumor effects cause prolonged hypogammaglobulinemia and B-cell aplasia. Limited data exist on pathogen-specific IgG titers post-CD19 CAR T-cell therapy.

Methods: We evaluated the impact of CD19 CAR T-cell therapy on vaccine-preventable infectious disease IgG titers in 20 patients to assess humoral immunity. IgG titers for measles virus (MeV), mumps virus (MuV), rubella virus (RuV), varicella zoster virus (VZV), pneumococcal capsular polysaccharide, Haemophilus influenzae type B (Hib), and tetanus toxoid were measured at baseline and Day 100 post-CD19 CAR T-cell therapy.

Results: Seropositivity for all pathogens remained stable from baseline to Day 100. Quantitative IgG titers for MeV, MuV, RuV, VZV, and tetanus also remained stable. Median pneumococcal IgG and Hib IgG titers declined (p < 0.05); however, no arbitrary fourfold decreases were observed. Median total IgG concentrations declined (p < 0.05).

Conclusion: MeV, MuV, RuV, VZV, and tetanus toxoid IgG remained stable following CD19 CAR T-cell therapy, while pneumococcal and Hib IgG titers showed marginal quantitative declines, without any fourfold reductions. Overall, humoral immunity at Day 100 following CD19 CAR T-cell therapy remained largely preserved. These seroprevalence findings suggest that routine revaccination may not be required in our patient cohort and highlight the importance of patient monitoring to inform revaccination decisions.

Background: Liver transplant recipients are at high risk of bacterial surgical site infection (SSI) following transplantation. However, they also have increased risks of antibiotic complications such as C. difficile and resistant organism infections. The optimal duration of perioperative antibiotic prophylaxis for liver transplantation is uncertain.

Methods: We analyzed infection outcomes in a total of 192 patients before and after a protocol change that shortened antibiotic prophylaxis duration at our institution. Durations were risk-stratified with longer durations for patients hospitalized prior to liver transplantation. The recommended duration of antibiotic prophylaxis changed from 5 days or until transfer out of intensive care to 3 days for patients hospitalized prior to transplant and from 2 days to 1 day for all other patients.

Results: There was no increased rate of SSI or bacteremia following the decrease in duration, with a change from 2.4% to 2.8% in patients hospitalized prior to transplant and 7.5% to 2.9% in other patients. Risk of SSI or bacteremia was not significantly increased in a multivariable model (OR 0.50, 95% CI 0.07-2.24; p = 0.41). There was no significant difference in readmission, graft rejection, graft failure, or mortality. Rates of acute kidney injury, C. difficile infection, and development of resistant organisms were not significantly different.

Conclusion: Shortening the duration of perioperative antibiotic prophylaxis in liver transplantation does not increase the risk of infection and may reduce harms of antibiotic exposure.

Background: Despite decreased morbidity and mortality in patients with cystic fibrosis (CF) with CFTR modulators, a significant percentage still develop advanced lung disease. Nontuberculous mycobacteria (NTM) remain challenging pathogens with unclear effects on disease progression and post-transplant outcome.

Methods: NTM-positive patients were identified from all CF patients treated at the University Hospitals of Zurich and Lausanne between 1998 and 2020. Disease course pre- and post-transplant was recorded, and NTM-positive patients were compared to patients without NTM infection for death or lung transplantation, as well as post-transplant survival and development of chronic lung allograft dysfunction (CLAD).

Results: Of 270 patients, 56 (20.7%) met criteria for NTM positivity (two independent cultures with the same organism), with Mycobacterium abscessus complex (MABSC) being the most common species (75.0%). Death or transplantation occurred in 12 of 56 (21.4%) NTM-positive patients and 92 of 198 (46.5%) NTM-negative patients (OR 3.17; 95% CI, 1.53-7.00; p = 0.001). Post-transplant mortality was higher in the NTM-positive cohort (3 (27.3%) vs. 12 (13.0%); HR, 4.01, 95% CI, 1.08-14.86; p = 0.024), while CLAD incidence did not differ significantly.

Conclusion: NTM-positive CF patients were associated with a lower pre-transplant risk of death or transplantation. Post-transplant mortality was higher in NTM-positive patients, while no association between NTM infection and CLAD was observed. These findings indicate that favorable outcomes after lung transplantation are achievable in NTM-positive patients. Thus, NTM-infection should not be an absolute contraindication for lung transplantation, though careful individual assessment is essential due to the risk of serious complications.

Background: Lung transplantation (LuTx) is hampered by infectious risks. Perioperative antibiotic prophylaxis (PAP) is widely used; however, real-time adjustment is hindered by the timing of standard microbiology. Syndromic molecular panels offer rapid results, yet their integration into PAP strategies remains unclear.

Methods: We conducted a prospective cohort study comparing the BioFire FilmArray Pneumonia Panel Plus (PNplus) with standard of care (SOC) on bronchoalveolar lavage (BAL) samples obtained from donors at procurement and from recipients 72 h after LuTx. Concordance between PNplus and SOC was assessed for bacterial species and antimicrobial resistance genes.

Results: Fifty-three donor-recipient pairs were analyzed. In donor BAL, PNplus identified at least one pathogen in 67.9% (36/53) of cases versus 63.5% (33/53) by SOC, with a markedly shorter time to result (221 min vs. 5.3 days). Concordance between PNplus and SOC for bacterial species was substantial (Cohen's κ = 0.654), particularly for Staphylococcus aureus (Cohen's κ = 0.689), Streptococcus pneumoniae (Cohen's κ = 0.658), and Pseudomonas aeruginosa (Cohen's κ = 0.731). In recipient BAL, PNplus detected pathogens in 61.5% (32/53) compared to 47.2% (25/53) with SOC, but overall concordance was only moderate (κ = 0.365). Resistance gene concordance was minimal, with PNplus often identifying additional determinants not confirmed by SOC. Viruses were detected exclusively by PNplus, while fungi were identified only by SOC.

Conclusion: PNplus provides rapid, clinically relevant pathogen detection in LuTx, showing substantial agreement with SOC in donor samples and offering potential to support PAP adjustment. In early post-transplant recipient BAL, interpretation requires caution, and SOC remains indispensable, particularly for detecting fungi and confirming phenotypic resistance.