Transplant Infectious Disease最新文献

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.

Background: The use of extended criteria donor lungs has increased, including lungs with chest radiograph (CXR) abnormalities. However, the clinical relevance of donor radiographic pneumonia (DRP) for lung transplant recipients is unclear.

Methods: This was a single-center retrospective cohort study of lung transplants between January 1, 2019 and August 1, 2023. Donors and recipients were included if donor imaging in the form of a CXR or computed tomography scout (CTS) was available within three calendar days of procurement and interpretable by two transplant pulmonologists for the presence of any possible pneumonia pattern. Outcomes in recipients with DRP were compared to those without DRP. Microbiological profiles were examined.

Results: Of 291 lung transplant recipients, 154 (52.9%) were included. Eighty-eight (57.1%) had DRP, and 90 (58.4%) had positive pre-procurement donor respiratory cultures. Comparing DRP recipients to those without, median recipient ventilator time was 4 versus 2 days (p = 0.44) and intensive care unit length of stay (LOS) was 9.5 versus 6.5 days (p = 0.07). DRP recipients had longer hospital LOS (25.5 vs. 20 days, p = 0.04). Posttransplant pneumonias within 30 days occurred in 26 (16.9%) recipients, mostly due to both donor- and recipient-derived Staphylococcus aureus and recipient-derived Pseudomonas aeruginosa.

Conclusion: DRP is associated with longer recipient hospital LOS but does not impact long-term survival. Respiratory pathogen isolation from donor lungs is common but may not be associated with posttransplant pneumonia.

Background: The use of antimicrobial agents in the preservation solution (PS) could prevent the bacterial transmission to recipients in organ transplantation. However, antibiotics may exhibit different decontamination efficacy in the hypothermic PS. This study aimed to evaluate the antibacterial activity of ceftazidime-avibactam (CAZ-AVI) combined with aztreonam (ATM) against multidrug-resistant bacteria (MDRB) at varying ratios and concentrations during 3 h, 0°C-4°C PS decontamination.

Methods: An in vitro model simulating PS decontamination was established. Five MDRB isolates were collected and tested (CRKP, CRPA, CREC, CRAB, and MRSA). CAZ-AVI and ATM were prepared at different ratios (1:1, 1:2, 1:4, 2:1) and concentration gradients (0.5×, 1×, 2×, 4× the baseline). Antibacterial efficacy was recorded and analyzed.

Results: For CRKP and CREC, the 2:1 ratio at 0.5× concentration (250 mg/L CAZ-AVI + 0.5 g/L ATM) showed significant antibacterial effects (p = 0.002 and p < 0.001, respectively). For CRPA, efficacy was observed at the 1× concentration with a 2:1 ratio (500 mg/L CAZ-AVI + 1.0 g/L ATM; p = 0.022), while for CRAB, the 1:1 ratio at 0.5× concentration (125 mg/L CAZ-AVI + 0.5 g/L ATM; p < 0.001) was effective. The combination was only effective against MRSA at high concentrations (1000 mg/L CAZ-AVI + 2.0 g/L ATM; p < 0.001).

Conclusions: The combination of CAZ-AVI and ATM effectively decontaminates MDR Gram-negative bacteria in PS. The 2:1 ratio at baseline concentration is recommended for clinical use, with potential escalation of CAZ-AVI concentration if needed.

Background: Patients with acute-on-chronic liver failure (ACLF) are susceptible to fungal infections. However, pretransplant invasive pulmonary Aspergillosis (IPA) is generally considered a relative contraindication for liver transplantation (LT).

Methods: We conducted a multi-center retrospective study involving ACLF adult patients with pretransplant IPA who underwent LT at four hospitals between January 2021, and June 2024. For comparative analysis, we included a control group of ACLF patients without preoperative Aspergillus infection during the same period, from the Renji Hospital cohort with matching approach. Posttransplant outcomes were then evaluated and compared between the two groups (ACLF patients with IPA vs. those without IPA).

Results: A total of 21 patients who had IPA before LT was identified. The mean age was 46.7 ± 9.2 years. The mean MELD score of these patients was 28.6. Most (71.4%, 15/21) patients received antifungal therapy immediately after the diagnosis of IPA. Twelve patients received voriconazole, one received isavuconazole, one received posaconazole, one received amphotericin B plus caspofungin and isavuconazole, the remaining six patients did not receive any antifungal drugs before LT. The median duration of antifungal therapy was 9 days (range: 0.5-34.5 days) before transplantation, overall median duration of antifungal treatment was 58 days (range: 22-83). The 3-month (38.1%, 8/21) and 12-month mortality (42.9%, 9/21) were significantly higher than patients without pretransplant IPA (p = 0.049 and p = 0.026, respectively).

Conclusions: The survival of LT for ACLF patients with pretransplant IPA was suboptimal, although they had received appropriate antifungal treatment within the peri-transplantation period. Multidisciplinary discussions before transplantation are necessary on case-by-case.

Background: Immune responses may determine natural history and optimal management of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic cell transplantation (alloHCT). To assess this, we performed serial QuantiFERON-CMV (QFCMV, Qiagen) and QuantiFERON-Monitor (QF-monitor, Qiagen) tests, measuring CMV-specific T cell interferon-γ responses (IFNγ), and stimulators of innate (TLR7) and adaptive immunity (CD3), respectively.

Methods: In a prospective multicenter study of adult CMV-seropositive alloHCT recipients, QFCMV and QF-monitor tests were collected serially. Association with CMV outcomes was analyzed using multivariable Cox and mixed effects regression analysis.

Results: Overall, 119 patients had 385 QFCMV tests (median [IQR]:3 [3-4] per patient). csCMVi occurred in 45.4% patients. QFCMV reactivity was achieved in 16% of patients at 6 weeks, 38.3% at 12 weeks, and 40.2% any time during the study. Reactivity was predictive of lower peak CMV viral load in the 6 weeks following testing (-0.41 × log₁₀ [95% CI -0.77 to -0. 04 × log₁₀], p = 0.02), but did not impact csCMVi. Analysis of mitogen-stimulated IFNγ responses within QFCMV testing showed reduced risk of csCMVi in the following 6 weeks (adjusted HR 0.92 [95% CI 0.85-0.99], p = 0.025) and each 1 IU/mL IFNγ increase was associated with decreased peak viral load (-0.02 × log₁₀ [95% CI -0.03 to 0.00 × log₁₀], p = 0.02). QF-monitor was not associated with any CMV outcomes.

Conclusion: QFCMV reactivity was associated with lower peak CMV viral load but not csCMVi. Mitogen-stimulated IFNγ response correlated with csCMVi, suggesting a role for broader assessment of cellular immunity post-transplant. Despite incorporating adaptive immunity measures, QF-monitor was limited in assessing CMV risk. QFCMV reactivity was infrequently achieved in the early post-allogeneic stem cell transplant period. Qualitative QFCMV result was associated with peak CMV viral load but not clinically significant infection, while magnitude of the mitogen response predicted reduction in clinically significant CMV infection.

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.