Transplant Infectious Disease最新文献

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: Recurrent urinary tract infections (rUTIs) are common in kidney transplant recipients (KTRs). We aimed to assess the impact of rUTI on medical morbidity and quality of life (QOL).

Methods: Single-center, retrospective review of adult KTRs with rUTI during March 1, 2022 to February 28, 2023. QOL was assessed via the Recurrent UTI Impact Questionnaire (RUTIIQ) using a 10-point Likert scale.

Results: Among 46 KTRs, the median age was 59.5 years, and 82.6% were women. Median time since transplant was 50.1 months; most were on tacrolimus, mycophenolate, and prednisone. Chronic kidney disease was present in 60.9%. Predominant uropathogens were Escherichia coli (54.3%) and Klebsiella pneumoniae (43.5%); 37% of patients had multidrug-resistant organisms. Sixty-five percent had UTI-related hospitalization, and 69.6% needed intravenous antibiotics during the study period. Among 27 survey respondents, patients had generalized anxiety (median score 7), disrupted sleep (median score 5), and anxiety regarding sex life (median score 8.5). Work and daily activities were impaired, with a median score of 9 for regularly missing days of work or home responsibilities due to UTI. While there was high satisfaction with the content of medical care (median score 9), lower scores were noted for aspects such as feeling listened to by healthcare providers (median score 4) and access to specialists (median score 3).

Conclusion: Recurrent UTI is associated with a significant impact on morbidity and adverse QOL in KTRs, with female recipients bearing a disproportionate burden. Clinicians must adopt a proactive approach to managing risk factors, optimizing graft function, and implementing prevention measures to minimize the burden of rUTIs in KTRs.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is increasingly used to treat systemic sclerosis (SSc). Data on post-AHSCT infections, including cytomegalovirus (CMV) in this population, are limited. This study aimed to assess risk factors, infection rates, and outcomes of post-transplant CMV infection following CD34-selected AHSCT for SSc.

Methods: We performed a single-center retrospective study of all AHSCT recipients for SSc complicated by CMV infection. A standardized pre-emptive CMV monitoring approach was employed throughout the study period (antiviral treatment threshold: plasma VL > 450 IU/mL). The primary outcome was the rate of CMV DNAemia or disease. Secondary outcomes included risk factors, management, and treatment outcomes.

Results: Among 42 AHSCT recipients, 19 (45%) were CMV-seropositive pre-transplant. CMV DNAemia occurred in 10/42 (24%) recipients post-transplant, of which 8/10 (80%) were CMV-seropositive. Median time to CMV DNAemia was 28 days (range: 21-35) post-transplant, with a median peak VL of 665 IU/mL (IQR: 340-1104). There were no cases of CMV disease. CMV seropositivity pre-transplant was a significant predictor of post-transplant CMV DNAemia (relative risk: 4.84, 95% CI: 1.16-20.14; p = 0.026). Of 10 patients with CMV DNAemia, six (60%) received CMV-targeted therapy while four (40%) resolved without treatment. Median duration of CMV targeted therapy was 35 days (IQR: 29-45). One patient (10%) experienced gastrointestinal intolerance necessitating antiviral discontinuation. No patient died or required hospitalization due to CMV infection.

Conclusions: CMV DNAemia following CD34-selected AHSCT occurred primarily in CMV-seropositive recipients. Though common, CMV DNAemia occurred early post-transplant and was associated with minimal morbidity.

Introduction: Respiratory viral infections (RVIs) such as influenza (Flu), respiratory syncytial virus (RSV), and parainfluenza (PIV) are associated with increased morbidity and mortality among immunocompromised patients.

Methods: A community-acquired (CA)-Flu/RSV/PIV case was defined as a positive laboratory result collected < 72 h after inpatient admission, whereas an HA-Flu/RSV/PIV case was defined as a positive result collected ≥ 72 h after inpatient admission.

Results: During the study period, 6.6% of Flu cases, 12.2% of RSV cases, and 10.9% of PIV cases were HA. Patients with a cancer diagnosis were more prevalent in the HA-Flu (24.3% vs. 11.8%) and HA-RSV (26.7% vs. 11.9%) groups compared to their CA counterparts. Patients who received chemotherapy within the past 30 days were more prevalent in the HA-Flu (10.8% vs. 4.4%), HA-RSV (20.0% vs. 8.1%), and HA-PIV (4.2% vs. 0.7%) groups compared to their CA counterparts. Recipients of SCT within the last year were more prevalent in the HA-Flu (6.3% vs. 2.3%) and HA-RSV (10.7% vs. 3.7%) groups compared to their CA counterparts. In the overall cohort, HA-Flu, HA-RSV, and HA-PIV were all associated with a higher likelihood of ICU admission. HA-Flu was additionally associated with a higher risk of mechanical ventilation, renal replacement therapy, and death compared to CA-Flu.

Discussion: Immunocompromised patients are heavily represented among HA cases, pointing to a need for targeted infection prevention and control interventions for vulnerable patient populations during periods of high RVI community transmission.

Background: Respiratory tract infections (RTIs) are a leading cause of morbidity and mortality following lung transplantation (LTx). This study evaluated a point-of-care multiplex-PCR testing system (POCTmPCR) for pathogen detection in various respiratory samples from LTx recipients.

Methods: In a prospective single-center study, LTx recipients with RTI undergoing bronchoscopy were enrolled. Samples from bronchoalveolar lavage (BAL), sputum, and nasopharyngeal swabs (NPS) were analyzed by POCTmPCR in conjunction with conventional diagnostics. The primary study endpoint was the concordance of POCTmPCR results between samples (DRKS00032359).

Results: Fifty participants with a median age of 48 years were included; 28 (56%) were previously colonized. Using POCTmPCR, 44 bacterial pathogens were identified in BAL from 30 patients, 49 in sputum (30 patients), and 33 in NPS (17 patients). POCTmPCR identified 24 viral pathogens in BAL from 20 patients, 22 pathogens in sputum of 19 patients, and 19 in NPS of 19 patients. For viral POCTmPCR, sensitivity and specificity compared to BAL were 84% and 97% in sputum, and 80% and 97% in NPS, respectively. For bacterial POCTmPCR, sensitivity and specificity were 80% and 67% in sputum, and 37% and 85% in NPS, respectively. POCTmPCR in comparison to conventional workup had a sensitivity of 89% and 80% and specificity of 75% and 76% for viral and bacterial pathogens, respectively.

Conclusion: POCTmPCR in nasal swabs and sputum may serve as an alternative to BAL for detecting respiratory viruses. Performance for bacterial detection in noninvasive samples was lower. The POCTmPCR system used lacks detection for SARS-CoV-2 and Aspergillus spp.

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.