cefoxitin and Obesity--Morbid

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 μg/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.

Topics: Adult; Antibiotic Prophylaxis; Body Weight; Cefoxitin; Dose-Response Relationship, Drug; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Obesity; Obesity, Morbid; Surgical Wound Infection; Tissue Distribution

Although >10% of surgical patients receive alternative antibiotic prophylaxis for reported penicillin allergies, it is estimated that <20% of such cases represent true allergies that preclude standard prophylaxis. Each antibiotic class has a distinct impact on the intestinal microbiota and on postoperative metabolomics. The community structure and function of the microbiota are linked to the ability to lose weight after bariatric surgery. This study demonstrates differential weight loss after laparoscopic sleeve gastrectomy between patients who received standard (cefoxitin) and alternative (levofloxacin and metronidazole) perioperative prophylaxis. Multivariate analysis demonstrates that alternative prophylaxis is significantly and independently associated with diminished postoperative weight loss.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bariatric Surgery; Cefoxitin; Female; Gastrectomy; Humans; Laparoscopy; Levofloxacin; Male; Metronidazole; Middle Aged; Obesity, Morbid; Postoperative Period; Retrospective Studies; Treatment Outcome; Weight Loss