Transplant Infectious Disease最新文献

Background: Lung transplant recipients (LTRs) frequently receive off-label inhaled tobramycin. However, LTRs differ pharmacokinetically from cystic fibrosis (CF) patients for whom the drug is approved and may be at increased risk for toxic systemic concentrations. This study characterized the incidence and predictors of detectable serum tobramycin concentrations among LTRs without underlying CF.

Methods: This retrospective, single-center cohort study included LTRs receiving inhaled tobramycin (without intravenous/intramuscular tobramycin) with serum concentration testing July 2015 to June 2025. Logistic regression identified predictors of elevated concentrations (tobramycin ≥ 1 µg/mL), and analysis of covariance evaluated the dose/concentration relationship controlled for timing. Acute kidney injury (AKI) was defined as ≥ 0.3 mg/dL or a 1.5× increase in serum creatinine.

Results: Forty-four LTRs (median age 69 years [IQR: 63-72]) contributed 56 tobramycin concentrations; 93% were inpatients, and 9% required renal replacement therapy (RRT). Inhaled tobramycin was dosed 160 mg (59%) or 300 mg (41%) twice daily. Detectable tobramycin serum concentrations occurred in 80% of patients (median 0.4 µg/mL [IQR: 0.3-0.8]); 8 (18%) had concentrations ≥ 1 µg/mL, and 3 (7%) ≥ 2 µg/mL. The 300 mg dose was associated with elevated concentrations (OR 7.2, 95% CI: 1.1-49.2, p = 0.043), including after adjusting for concentration timing (p < 0.001). Among non-RRT patients, 55% developed new AKI a median of 3 days after concentration sampling, with tobramycin concentrations significantly higher in the AKI group (0.4 µg/mL vs. 0.2 µg/mL, p = 0.035).

Conclusion: LTRs without CF commonly had systemic tobramycin exposure during inhaled therapy. The 300 mg dose was linked to higher serum concentrations, supporting reduced dosing and active serum concentration monitoring to enhance safety.

Background: During kidney transplantation, the use of a ureteral stent reduces the risk of major urological complications (MUC). However, it is associated with infectious complications and usually requires a second procedure to be removed. The goal of this pilot study was to evaluate the impact of early ureteral stent removal at bedside.

Methods: We prospectively included all consecutive kidney transplant recipients at our center between May 2020 and May 2021. During the first 6 months, all consecutive patients had routine removal of the ureteral stent as an outpatient procedure (Group 1). During the last 6 months, all patients had early removal of the ureteral stent at bedside before leaving the hospital, using a grasper-integrated single-use flexible cystoscope (Group 2). The primary endpoint was feasibility and patient satisfaction. Secondary endpoints were rate of urinary tract infections (UTI) and major complications.

Results: Overall, 151 patients were included, 84 in Group 1 and 67 in Group 2. The characteristics of the two groups were similar. There was no failure of the bedside early stent removal procedure, with a mean overall satisfaction score of 9/10 (rank: 4-10). The rate of MUC was similar in the two groups. In multivariate analysis, early removal of the ureteral stent was a significant predictor of a lower risk of UTI (OR = 0.49; IC95% [0.23; 0.98]; p = 0.047).

Conclusion: Early bedside ureteral stent removal was feasible, with a high satisfaction rate and a lower risk of UTI without a significant increase of MUC.

Background: The present study aimed to assess the incidence of active TB, risk factors associated with TB and KT outcomes among a group of KTR from Romania.

Methods: This single-center, nested case-control study, included 22 KTR with active TB and 88 KTR without active TB (matched 1:4) identified from 1485 patients who underwent KT at Fundeni Clinical Institute between 2002 and 2017.

Results: The incidence of active TB among the cohort was 1.48% with a median time to occurrence of 60.26 months (IQR: 30.75-102.50) after KT. Multivariate conditional logistic regression showed that history of active TB before KT (OR = 17.97 [95% CI: 1.35-238.22], p = 0.02) and anti-thymocyte globulin induction (OR = 2.14 [95% CI: 1.10-4.24], p = 0.02) were independent risk factors associated with TB development. Patient survival (p = 0.03), overall (p < 0.001) and death-censored graft survival (p < 0.001) were significantly lower in KTR with active TB than in controls during the follow-up period. Kidney function was not significantly different between TB cases and controls at the last follow-up (p = 0.57) in an adjusted analysis.

Conclusion: This study was the first to evaluate active TB in KTR from Romania and found a higher incidence of active TB than that in the general population and a late onset of infection. TB had a negative impact on both patient and graft survival. Screening for latent TB, judicious prophylaxis, rigorous monitoring after KT and tailoring of the immunosuppression could be effective strategies to reduce the burden of TB among KTR.

Background: Recipient cytomegalovirus (CMV) serostatus reassessment proximate to transplant for initially CMV seronegative patients is critical to guide post-transplant CMV preventive strategies in kidney transplant recipients (KTR), since seroconversion during the long wait-list time could lead to CMV serostatus misclassification. The feasibility and optimal timing of CMV serostatus reassessment and the incidence of seroconversion have not been systematically examined.

Methods: Program adherence to a guideline for CMV serology reassessment within 6 months of transplant among initially CMV seronegative adults undergoing a first kidney transplant between December 17, 2022 and December 17, 2024 was retrospectively assessed. The association of baseline and transplant factors with adherence was compared by chi-square or Fisher's exact test (p < 0.05 considered significant). The incidence of CMV seroconversion between the time of listing and transplant was calculated per person-years of follow-up.

Results: Among 823 adult KTR, 586 (71.2%) were eligible and 127 (21.7%) were CMV seronegative at listing. The median (interquartile range) time to transplant was longer for deceased (5.23 [2.86-7.44] years) than living donor KTR (1.51 [0.76-2.74] years). Program adherence was 91.3% (116/127) overall and higher among living (65/65 [100%]) versus deceased donor transplants (51/62 [82.3%]), p < 0.01). No demographic or transplant-related variables were associated with adherence (p > 0.05 for all variables). Seroconversion between listing and transplant occurred in two of 124 patients (1.6%), an incidence of 0.0043 per person-year of follow-up.

Conclusion: Program adherence to CMV serostatus reassessment within 6 months of transplant was high in a clinical setting and identified a low incidence of seroconversion.

Background: Due to its relatively low incidence in developed countries, tuberculosis (TB) is rarely considered in differential diagnosis, even among immunocompromised patients. However, with shifting epidemiological patterns, the threat is underestimated. The aim of this study was to describe epidemiology, clinical characteristics, treatment, and outcome of TB in pediatric patients with malignancy and hematopoietic stem cell transplant (HSCT) recipients in Poland.

Methods: Five cases of TB were reported from all Polish pediatric hematology, oncology, and transplant centers among patients diagnosed with malignancies or those who underwent HSCT over the period from 2012 to 2023. The infections were categorized into two groups: the malignancy group (n = 1; 20%) and the HSCT group (n = 4; 80%).

Results: Within the malignancy subgroup, a single case of TB occurred in a female patient aged 1.9 years, who was treated for relapse of B-cell precursor acute lymphoblastic leukemia (BCP ALL). She developed extrapulmonary TB with lymph node involvement. In the HSCT subgroup, four TB cases were identified in three girls and one boy, with a median age of 0.7 years. All patients had undergone HSCT due to primary immunodeficiencies. The BCP ALL patient was treated with rifampicin and isoniazid. Among the HSCT patients, two received combination therapy with rifampicin, isoniazid, ethambutol, and streptomycin. One patient was treated with rifampicin and isoniazid, and another patient received rifampicin monotherapy. Two children died: BCP ALL patient due to disease progression and transplanted patient because of TB progression.

Conclusions: TB should be considered in the differential diagnosis of immunocompromised patients.

Background: Sickle cell disease (SCD) can be cured by hematopoietic cell transplantation (HCT), but patients face increased risk of hepatitis B virus (HBV) reactivation due to immunosuppression. Understanding hepatitis B surface antibody (anti-HBs) kinetics is essential for optimizing HBV revaccination and posttransplant care.

Methods: This post hoc analysis examined HBV immunity, reactivation, and revaccination response in 71 SCD patients who underwent HCT at the National Heart, Lung, and Blood Institute (2008-2021) using alemtuzumab and low-dose total body irradiation.

Results: At baseline, 55% showed HBV immunity (anti-HBs ≥ 12 mIU/mL). Most patients responded to revaccination regardless of baseline immunity. Post-HCT revaccination was given to 93%, with 89% completing full series (Heplisav-B or Engerix-B). Vaccinated patients had a 67.5% chance of increased anti-HBs titers between Years 1 and 2, though no significant difference was seen compared to unvaccinated patients (p = 0.12). No HBV reactivation occurred; two patients with baseline HBcAb and HBsAg positivity showed decreasing HBV DNA levels.

Conclusions: Results indicate that HBV immunity can decline post-HCT, but most patients remain immune, and revaccination is effective. However, some non-responders-especially those treated with IVIG, rituximab, or prolonged immunosuppression-need further study. Prospective research is needed to optimize revaccination timing and immune monitoring in this high-risk group.

Background: Therapeutic drug monitoring (TDM) is recommended for posaconazole oral immediate release suspension due to saturable absorption and variable bioavailability; however, it has been suggested that TDM may not be necessary for the delayed-release tablet or intravenous formulations. Our study evaluated target trough attainment with the delayed-release tablet and intravenous solution.

Methods: This retrospective, single-center study included adult patients who received posaconazole at a dose of 300 mg every 24 h with at least one steady-state (SS) trough while on the delayed-release tablet or intravenous solution exclusively. Outcomes included the percentage of patients who achieved an initial SS trough ≥ 1300, ≥ 1000, or ≥ 700 ng/mL, in addition to a risk factor analysis.

Results: Among the 142 patients included, 74 (52.1%), 102 (71.8%), and 122 (86%) patients had an initial SS trough ≥ 1300, ≥ 1000, and ≥ 700 ng/mL, respectively. More patients achieved an initial SS trough ≥ 1300 ng/mL under the following conditions: total body weight < 90 kg, body mass index < 30 kg/m², or no receipt of acid suppressive therapy. No significant differences were found for median initial SS troughs or percentage of patients with an initial SS trough ≥ 1000 or ≥ 700 ng/mL.

Conclusion: With 47.9% of initial SS troughs < 1300 ng/mL and 28.8% < 1000 ng/mL, we recommend TDM for all patients receiving posaconazole for treatment, irrespective of formulation. Initial doses higher than 300 mg q24h should be considered for all patients and strongly considered for patients with risk factors for subtherapeutic troughs.

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.