Transplant Infectious Disease最新文献

Background: Treating Mycobacterium avium complex (MAC) infection pre-lung transplant (LT) can be challenging to treat, given prolonged therapy and side effects. The impact of pre-transplant MAC treatment on recurrence and outcomes post-LT remains unclear, especially in patients with interstitial lung disease (ILD) who have a median survival of less than 2 years.

Methods: We performed a retrospective cohort study of adult LT patients at the Mayo Clinic who had positive MAC sputum cultures pre-LT. The cohort was stratified and compared based on the type of treatment (complete, partial, or no treatment) for MAC pulmonary infection. The primary outcome was MAC recurrence post-LT, and secondary outcomes were mortality, FEV-1, and FVC at 1-year post-LT.

Results: Among the cohort of 47 patients, 9 (19.1%) were partially treated and 11 (23.4%) were completely treated for MAC infection pre-LT. Post-transplant MAC pulmonary infection recurrence occurred in eight (17%) of the total cohort, with four (14.8%) in the non-treated, four (44.4%) in the partially-treated, and none (0%) in the completely treated patients (p = 0.026). There was no difference in mortality in patients who had MAC recurrence post-transplantation (13% vs. 9.7%, p > 0.9) and those who were completely or partially treated, compared to non-treated (0% vs. 13% vs. 13%, p > 0.9). The FEV1 and FVC at 1-year post-LT did not differ by the pre-transplant treatment or post-transplant MAC recurrence status.

Conclusion: The role of treatment for MAC infection pre-transplant is questionable, especially in patients with diseases like ILD who may not have enough wait time to complete therapy.

Background: Vancomycin plus an antipseudomonal β-lactam are common antibiotics used for lung transplant surgical prophylaxis, but the optimal post-operative duration is unknown. The study objective was to assess the impact of a shortened antibacterial surgical prophylaxis duration on post-operative acute kidney injury (AKI) in lung transplant recipients.

Methods: This was an IRB approved, single pre-/post-test quasi-experiment of lung transplant recipients who received post-operative antibiotic prophylaxis from January 1, 2016-September 30, 2020 (pre-group) to October 1, 2020-March 31, 2025 (post-group). The intervention included modifying vancomycin (and cefepime) post-operative prophylaxis durations to 72 h; the previous prophylaxis standard included continuing vancomycin until chest tube removal. The primary endpoint was incidence of AKI, defined by the KDIGO criteria, while receiving post-operative vancomycin up to 14 days. Thirty-day secondary outcomes included surgical site infection (SSI), treatment of lower respiratory-tract infection, and isolation of multi-drug-resistant organisms (MDRO).

Results: Ninety patients were included-45 pre- and 45 post-intervention. Most patients were men (64.4%) and had a median (IQR) age of 63 (58-68) years. The most common indication for transplant was pulmonary fibrosis (37.8%). The incidence of 14-day AKI was reduced when comparing pre- and post-intervention groups (48.9% vs. 28.9%, p = 0.052), with no differences in SSI (2.2% vs. 2.2%, p = 1.0), treatment of lower respiratory tract infection (57.8% vs. 73.3%, p = 0.120), and isolation of MDRO (15.6% vs. 13.3%, p = 0.764). When accounting for baseline renal function, patients in the post-intervention group had a significantly decreased odds of AKI (adjOR, 0.385; 95%CI, 0.154-0.959).

Conclusion: Implementation of a shortened post-operative vancomycin prophylaxis duration protocol was associated with reduced odds of AKI in lung transplant recipients, with similar post-operative infectious complications.

Infection with Dengue virus (DENV)is a growing concern in solid organ transplant (SOT) recipients in endemic regions. We report a 15-year-old kidney transplant recipient who developed fever and thrombocytopenia on post-transplant day five; DENV NS1 antigen confirmed acute infection. He recovered with supportive care, and no donor-derived transmission was identified. A review of 327 cases shows early post-transplant dengue carries higher risks of cytopenias, capillary leak, graft dysfunction, and mortality (6.1%) versus the general population. Improved diagnostics, outbreak-responsive donor screening, and pre-transplant vaccination in immunocompetent candidates may help mitigate dengue burden in SOT recipients.

Background: Solid organ transplant (SOT) recipients are vulnerable to infections with multidrug-resistant organisms, and they often do not receive adequate empiric antimicrobials for serious Gram-negative infections. Knowledge of differences in antimicrobial resistance rates in this specific population can help guide empiric antimicrobial choices.

Methods: We performed a retrospective cohort study comparing antimicrobial susceptibility patterns of Gram-negative organisms isolated from the adult SOT recipients with documented sepsis with the hospital-wide inpatient antibiogram. To evaluate empiric antimicrobial coverage, we constructed a Weighted-Incidence Syndromic Combination Antibiogram (WISCA) by calculating the proportion of susceptible isolates per antimicrobial agent. We then compared the coverage rates against our institution's sepsis treatment guidelines.

Results: A total of 90 Gram-negative isolates comprised the SOT cohort, while the inpatient antibiogram cohort had 1328 isolates. Pseudomonas aeruginosa (27%) and Escherichia coli (31%) were the most common isolates in the SOT and inpatient antibiogram cohorts, respectively. Overall, antimicrobial resistance rates were higher in the SOT population compared to the hospital-wide inpatient antibiogram population. WISCA analysis showed imipenem was active for 59% of isolates as opposed to the institutional recommendation of piperacillin-tazobactam, which covered 39% of SOT isolates.

Conclusion: Current empiric antimicrobial recommendations for SOT patients are based on data from the general patient population, which may not accurately reflect the resistance patterns in this unique population. Utilizing patient population-specific antibiograms may improve empiric antimicrobial therapy and warrants further research.

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.

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.

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.