188: PHARMACOKINETIC ANALYSIS OF ANTIMICROBIAL THERAPY IN VENTRICULAR ASSIST DEVICE-SUPPORTED PATIENTS

Introduction: As a result of underlying heart failure, the utilization of left ventricular assist devices (VAD) has increased as a means of offloading the failing ventricle to improve cardiac output. Importantly, after device implantation and once end-organ perfusion has been enhanced, new pharmacokinetic alterations may acutely develop which may require pre-emptive dose adjustments for several pharmacotherapies. Currently, there are limited data in patients with VADs to determine patient and population-specific antimicrobial disposition. The purpose of this study is to assess perioperative pharmacokinetic changes in patients during VAD implantation receiving prophylactic antibiotics. Methods: Patients will be prospectively enrolled to collect blood samples peri-operatively and post-operatively. Blood samples will be used to analyze the antimicrobial concentrations using a validated high-performance liquid chromatography (HPLC-UV) assay. Results: To date, 11 patients have been enrolled in this study. Enrollees are on average 63 years of age, predominately male (82%), with nonischemic cardiomyopathy (64%). LVAD implantation consisted of HeartMate3 (n=9), and HVAD devices (n=2). Standard prophylactic regimens for LVAD implantation include ceftazidime and vancomycin. Intra-operatively, all patients received one prophylactic dose of ceftazidime 2 grams from which samples were collected thereafter. The median samples collected intra-operatively was 4 (IQR 3,6). Post-operatively, ceftazidime prophylaxis was continued for 36 hours, and samples were typically collected after the third ceftazidime dose. The median samples collected post-operatively was 4 (IQR 4,5). Antimicrobial plasma concentrations are currently pending processing and analysis. The drug concentration in the serum will be analyzed to determine the maximum concentration, area under the concentration-time profile for the dosing interval, half-life, clearance, and volume of distribution. Conclusions: In this medically complex heart failure patient population, use of narrow therapeutic index drugs can have detrimental consequences if they are not dosed appropriately. This study will provide practitioners more insight in perioperative dosing regimens for VAD patients by understanding how serum drug levels may be altered with VAD therapy.