The objective of this study was to determine the pharmacokinetics and pharmacodynamics (PK/PD) of a weight-based cefoxitin dosing regimen for surgical prophylaxis in obese patients. Patients received a single dose of cefoxitin at 40 mg/kg based on total body weight. Cefoxitin samples were obtained over 3 h from serum and adipose tissue, and concentrations were determined by validated high-performance liquid chromatography. Noncompartmental pharmacokinetic analysis was performed, followed by Monte Carlo simulations to estimate probability of target attainment (PTA) for Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis over 4-h periods postdose. Thirty patients undergoing bariatric procedures were enrolled. The body mass index (mean ؎ standard deviation [SD])was 45.9 ؎ 8.0 kg/m 2 (range, 35.0 to 76.7 kg/m 2 ); the median cefoxitin dose was 5 g (range, 4.0 to 7.5 g). The mean maximum concentrations were 216.15 ؎ 41.80 g/ml in serum and 12.62 ؎ 5.89 in tissue; the mean tissue/serum ratio was 8% ؎ 3%. In serum, weight-based regimens achieved >90% PTA (goal time during which free [unbound] drug concentrations exceed pathogen MICs [fT>MIC] of 100%) for E. coli and S. aureus over 2 h and for B. fragilis over 1 h; in tissue this regimen failed to achieve goal PTA at any time point. The 40-mg/kg regimens achieved higher PTAs over longer periods in both serum and tissue than did the standard 2-g doses. However, although weight-based cefoxitin regimens were better than fixed doses, achievement of desired pharmacodynamic targets was suboptimal in both serum and tissue. Alternative dosing regimens and agents should be explored in order to achieve more favorable antibiotic performance during surgical prophylaxis in obese patients. Surgical site infections (SSIs) are the leading cause of postoperative morbidity and mortality and add significantly to the cost of care (1). Perioperative antibiotic prophylaxis is therefore a standard of care and a keystone for the prevention of SSIs (2-6). Recommendations regarding the use of specific antibiotics for prophylaxis during surgical procedures have been published since the early 1990s and have been frequently revisited since that time (1, 2, 5-9). More recently, specific recommendations provided by the National Surgical Infection Prevention (SIP) Project have focused on appropriate timing of administration of prophylactic antibiotics, appropriate drug selection, and the discontinuation of prophylactic antibiotics within 24 h after surgery (2, 9). However, the actual recommended drugs and dosing regimens for surgical prophylaxis have been relatively unchanged over the past 20 years. Limited published data exist regarding appropriate dosing of antimicrobials for prophylaxis. It is generally stated that the drug should be given in an adequate dose based on patient weight, adjusted dosing weight, or body mass index (BMI) (2, 6, 9). Furthermore, antibiotic administration should be repeated intraoperatively if the procedure continues beyond one to two pharmacokinetic (PK) hal...

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These data should be considered as states expand Medicaid and make decisions regarding treatment of severe obesity. Interventions to decrease hospital LOS and the 30-day readmission rate, particularly in Medicaid patients, should be explored.

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