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Online ISSN 1827-1596
Borracci T. 1, Adembri C. 1, Accetta G. 2, Berti J. 1, Cappellini I. 1, Lucchese M. 3, Biggeri A. 2, 4, De Gaudio A. R. 1, Novelli A. 5
1 Department of Health Sciences Section of Anesthesiology and Intensive Care;
2 Department of Bariatric Surgery Azienda Ospedaliero-Universitaria Careggi, Florence, Italy;
3 Biostatistics Unit, ISPO Cancer Prevention and Research Institute, Florence, Italy;
4 Department of Statistics “G. Parenti”, University of Florence, Florence, Italy;
5 Department of Health Sciences, University of Florence, Florence, Italy
BACKGROUND: The objective of this study was to determine the pharmacokinetics-pharmacodynamics (PK/PD) of Ertapenem in extremely obese female patients (Body Mass Index [BMI] ≥40 kg/m2) undergoing bariatric surgery.
METHODS: Ten patients received 1 g intravenous Ertapenem 0.5 h 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 4-8, 8-12, and 12-24 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 24-h area under the concentration-time curve (AUC) were found to be 191.9±37.4 mg/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 4-8h, declined to 15.2±5.9 at 8-12h and fell further to 4.79±0.2 mg/L at 12-24 h post-administration. The probability to reach the desired PK/PD targets were never reached at any MICs >0.25 µg/mL with a 90% probability.
CONCLUSION: 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.