Nair, Vaisak O

ABSTRACT Background Cytomegalovirus (CMV) infection remains one of the most prevalent and consequential post solid organ transplant (SOT) infections. Treatment is often challenging, especially when dealing with refractory and resistant CMV infections. Methods We performed a retrospective multicenter cohort study of SOT recipients with clinically significant CMV infection (csCMVi) during 2010–2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Analysis was done with Kaplan‐Meier, univariable logistic regression analysis, and multivariable Cox regression. Results We included 145 SOT recipients with csCMVi, majority were liver transplant (49%). Most common induction was an anti‐IL‐2 antibody (43.9%). The majority ( n = 82; 56.5%) were CMV D+/R‐ mismatch and presented asymptomatic infection (50.3%). After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R‐ mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48–0.95, p = 0.029) while lower absolute lymphocyte count (ALC) had a higher risk of early refractory csCMVi (OR 1.54; CI 1.01–2.44, p = 0.048). Drug‐resistant csCMVi occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2.00; CI 1.08–3.93, p = 0.031). 25 patients (17.2%) experienced recurrent csCMVi within 6 months. 30 patients (20.7%) died; refractory, resistant or recurrent CMV infections were not associated with mortality. Conclusion Refractory csCMVi is associated with a low ALC and an earlier onset after transplant. Resistant csCMVi is associated with high initial CMV DNA levels. Recurrence of csCMVi is common and potentially associated with low ALC at the end of antiviral treatment.

ABSTRACT Purpose The purpose of this study was to evaluate the incidence and risk factors for developing recurrent clinically significant cytomegalovirus infections (csCMVi) in heart transplant recipients. Methods We conducted a retrospective cohort study involving adult heart transplant recipients at three large transplant centers in the United States between January 2011 and March 2019. All patients with a history of csCMVi, defined as CMV disease or CMV infection requiring preemptive therapy, were followed from the date of treatment completion for the primary csCMVi episode. Outcomes of interest were recurrent csCMVi and all‐cause mortality. Results Among 98 heart transplant recipients with csCMVi, 22 (22.4%) episodes of recurrent csCMVi occurred. Median time‐to‐recurrent csCMVi was 31.5 (IQR 21.3–59.8) days following treatment completion. A preceding episode of CMV disease (versus infection) was associated with a lower risk of recurrent csCMVi (HR 0.29, 95% CI 0.08–0.98; p = 0.047). Patients with lymphopenia had higher rates of recurrent csCMVi without statistical significance (HR 2.13, 95% CI 0.88–5.13; p = 0.093). Seroconversion by the end‐of‐therapy among CMV D+/R− mismatched patients was associated with a reduced risk of csCMVi recurrence (HR 0.07, 95% CI 0.02–0.30; p < 0.001). Overall, 17 (17.3%) patients died during follow‐up, which was not significantly higher among those with recurrent csCMVi (HR 2.13, 95% CI 0.78–5.79; p = 0.141). Conclusions About one in five heart recipients with csCMVi developed post‐treatment recurrence. A preceding episode of CMV disease and seroconversion was protective against recurrence. Lymphopenia may be a practical biomarker to stratify recurrence risk. Overall, recurrent csCMVi was not significantly associated with mortality.

Abstract Objectives To compare the efficacy and safety of antibiotic lock therapy (ALT) versus catheter removal in managing central vascular catheter–associated bloodstream infection (CVC-BSI). Methods We conducted a single-centre, retrospective cohort study of adult patients treated with ALT or catheter removal for management of CVC-BSI between 2018 and 2022. The primary outcome was a composite of 90 day microbiological relapse or recurrent BSI. Secondary outcomes included 30 day mortality, CVC-associated complications and Clostridioides difficile infection (CDI). Logistic regression with propensity score-adjustment was used to evaluate differences in outcomes and identify predictors of relapse. Results During the study period, 106 participants received ALT and 181 underwent catheter removal. Patients treated with ALT received shorter courses of systemic antimicrobials (11 versus 14 days; P &lt; 0.001) and had shorter hospital stays (4 versus 10 days; P &lt; 0.001). Median duration of catheter salvage in patients receiving ALT was 28 days (IQR 7–80). Primary composite outcome was similar between both groups, but ALT was associated with a significantly higher risk of microbiological relapse within 90 days (20% versus 7%; adjusted odds ratio 3.93, 95% CI 1.64–9.40; P = 0.002). No significant difference in 30 day mortality, CVC-related complications or CDI was observed. CoNS BSI was an independent predictor of microbiological relapse in patients treated with ALT (OR 2.28; P = 0.05). Conclusions Although ALT offers a non-invasive catheter salvage strategy, its association with higher relapse rates, particularly in CoNS BSI, suggests catheter removal should remain the preferred approach when feasible. ALT could be considered a short-term catheter salvage strategy for pathogens with low virulence when used with close surveillance.

ABSTRACT Introduction With reports of expanding epidemiology of blastomycosis across the United States, the purpose of this study was to evaluate the incidence and outcomes associated with blastomycosis in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients. Methods We conducted a retrospective case series of adult SOT and HCT recipients at a tertiary care medical center between January 1, 2005 and September 30, 2023. Cases were defined as culture‐proven blastomycosis. We performed descriptive statistical analysis to evaluate diagnosis, management, and outcomes (mortality) of blastomycosis in SOT. Results The cumulative incidence of blastomycosis was 0.11% with a median time to infection following transplant of 743 days. Of the 19 cases, the majority of patients were SOT recipients (90%). Supratherapeutic immunosuppression within 30 days of diagnosis was observed in 42% of cases with documented drug monitoring. Urine antigen testing was highly sensitive (100%). Fourteen (73.7%) patients received induction therapy with liposomal amphotericin B followed by azole therapy for a minimum of 12 months. Despite appropriate treatment, 1‐year mortality was high at 26.3%, with attributable mortality of 21.1%. Conclusions While rates of blastomycosis remain low among SOT and HCT recipients, infection is associated with poor posttransplant outcomes. Antigen testing can aid in timely assessment of disease severity and initiation of appropriate therapy. Among survivors, no relapses were observed while on lifelong secondary suppression. Future studies should aim to better define risk factors associated with developing blastomycosis and establish effective strategies for prevention.