Evaluation of clotrimazole prophylaxis on tacrolimus trough concentrations in kidney transplant recipients.

BACKGROUND: Clotrimazole troches are used as prophylaxis against oropharyngeal candidiasis post-transplant and have limited systemic absorption. Following several occurrences of tacrolimus concentration fluctuations after clotrimazole discontinuation, its use as prophylaxis was discontinued post-kidney transplant. METHODS: We conducted a retrospective cohort study to evaluate the effect of clotrimazole prophylaxis on tacrolimus trough concentrations post-kidney transplant. The study included adult patients who received a kidney transplant at Cleveland Clinic Main Campus from August 1, 2019 to July 1, 2020 and were maintained on per-protocol, standard-dose tacrolimus through 90 days post-transplant. Patients were excluded if they received cyclosporine, systemic antifungals, strong CYP3A4 inhibitors or inducers, or a simultaneous multiorgan transplant. The primary objective was to compare tacrolimus trough concentrations before and after completion of clotrimazole prophylaxis. Secondary objectives were to compare the time to first post-transplant goal tacrolimus trough concentration, the rate of for-cause allograft biopsies within 90 days after transplant, and the incidence and type of candidiasis within 30 days after transplant, pre- and post-protocol change. RESULTS: Following clotrimazole discontinuation, the median tacrolimus trough concentration decreased from 10.5 ng/ml (IQR 8.4-12.2) to 6.6 ng/ml (IQR 5-8.7, p < 0.0001). No statistically significant differences in the rate of for-cause allograft biopsies (4.9% vs. 9.7%, p = 0.264) or incidence of candidiasis (1.2% vs. 5.4%, p = 0.217) were observed between those who received clotrimazole and those who did not receive clotrimazole. CONCLUSIONS: Our study provides further evidence of a significant drug-drug interaction between tacrolimus and clotrimazole among kidney transplant recipients that can potentially lead to negative allograft outcomes.

Evaluation of Prophylactic Antibiotic Use for Delayed Sternal Closure After Cardiothoracic Operation.

BACKGROUND: Clinical practice guidelines provide recommendations for surgical prophylaxis in patients undergoing cardiothoracic procedures. However, currently no recommendations guide the management of antibiotic prophylaxis in patients who require delayed sternal closure after cardiothoracic operation. METHODS: This is a single-center, retrospective analysis. Data were extracted from The Society of Thoracic Surgery database and electronic medical record from July 2011 through January 2016. Patients included are adults (≥18 years old) after cardiothoracic operation with delayed sternal closure. RESULTS: A total of 167 patients were included for analysis. The majority of patients (131, 78.4%) were continued on routine antibiotics and 36 patients (21.6%) were switched to broad-spectrum antibiotics for prophylaxis. Of patients on routine antibiotic prophylaxis, 6 (4.6%) experienced a sternal surgical site infection, whereas 3 patients (8.3%) switched to broad-spectrum agents before chest closure experienced a sternal surgical site infection (p = 0.407). Eleven patients (6.6%) received an abbreviated duration of antibiotics, 52 patients (31.1%) were continued on antibiotics until the time of sternal closure, and 104 patients (62.3%) were continued on antibiotics past the time of sternal closure. The incidence of infection based on duration of prophylactic antibiotic was 0, 1 (1.9%), and 8 (7.7%), respectively (p = 0.352). CONCLUSIONS: Substantial variation was found in the duration and selection of antibiotic prophylaxis for patients with delayed sternal closure after cardiothoracic operation. Broad-spectrum antimicrobial agents and extended durations of antibiotic prophylaxis were not associated with benefits in the incidence of sternal wound infection and may increase the risk of adverse effects.

Comparative Effectiveness and Safety Analysis of Dual Antiplatelet Therapies Within an Integrated Delivery System.

BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes. OBJECTIVE: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding. RESULTS: A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis. CONCLUSIONS: Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.