USE OF THE PARENTERAL ANTIBIOTIC ERTAPENEM AS SHORT TERM PROPHYLAXIS IN BARIATRIC SURGERY: A PHARMACOKINETICPHARMACODYNAMIC STUDY IN CLASS III OBESE FEMALE PATIENTS.

Objectives: The objective of this study was to determine the pharmacokineticspharmacodynamics (PK/PD) of Ertapenem in extremely obese female patients (body mass index [BMI] 40 kg/m2) undergoing bariatric surgery. Methods: Ten patients received 1g intravenous Ertapenem 0.5h prior to surgery as short term prophylaxis. Serum Ertapenem concentrations were determined at baseline, at the end of infusion (30 minutes), then at 1,2, 4, 8, 12 and 24 hours postinfusion. In patients in whom a liver biopsy was necessitated by clinical need, Ertapenem liver concentrations were determined through intraoperative biopsies at 1 and 2 h postadministration. Peritoneal Ertapenem concentrations were determined in drainage fluid samples collected during the 48, 812, and 1224 h intervals after Ertapenem administration. A Monte Carlo simulation was performed to estimate the probability of achieving free drug levels above the minimum inhibitory concentration (fT>MIC ) for at least 20% and 40% of the dosing interval as PK/PD targets. Results: Peak drug concentration and 24h area under the concentrationtime curve (AUC) were found to be 191.9±37.4mg/L and 574.3+110.5mg∙h/L, respectively. Ertapenem liver/serum concentration ratios were 6% at 1 h and 5% at 2 h. Drug concentrations in peritoneal fluid were 28.2+6,4 mg/L at 48h, declined to 15.2 + 5.9 at 812h and fell further to 4.79+0.2 mg/L at 1224 h postadministration. The probability to reach the desired PK/PD targets were never reached at any MICs >0.25 μg/ml with a 90% probability. Conclusions: Our data suggest that in extremely obese female patients, the standard dose of 1 g i.v. Ertapenem as short term prophylaxis may not provide optimal clinical levels of free drug for prevention of surgical site infections.