Ertapenem Concentrations in Obese Patients Undergoing Surgery

Background: Antimicrobial prophylaxis is a cornerstone to preventing surgical site infections (SSIs). Ertapenem, a carbapenem antibiotic, is commonly used for surgical prophylaxis for many different procedures, including patients undergoing colorectal and other gastrointestinal surgeries. Obesity complicates surgical intervention and increases the risk for SSIs. This study aims to describe the pharmacokinetics of ertapenem for surgical prophylaxis using a population pharmacokinetic model. Patients and Methods: Ten patients were recruited and given a single dose of ertapenem 1 g intravenous over 30 minutes. Plasma samples were obtained at multiple time points over 24 hours and assayed via validated high-performance liquid chromatography (HPLC). Pharmacokinetic analyses were conducted using a population pharmacokinetic analysis to generate pharmacokinetic parameters used in the subsequent 5,000 patient Monte Carlo simulation. The probability of target attainment (PTA) for free drug concentrations remaining above the minimum inhibitory concentration (MIC) for ≥40% was used. Results: The mean maximum plasma concentration and area under the concentration time curve (AUC 0-∞ ) was 40.7 ± 16.5 and 148.8 ± 28.0, respectively, with a half-life of the terminal portion to be 4.3 ± 0.8 hours. Monte Carlo simulations observed PTAs above 90% for MICs ≤0.25 and ≤0.125 mcg/mL in surgeries up to three and four hours, respectively. Sufficiently high PTAs were not attainable for MICs of ≥0.5 mcg/mL. Conclusions: Ertapenem given as 1 g single dose may be an appropriate candidate for surgical prophylaxis in obese patients undergoing surgeries of four hours or less.