title: Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients.
abstract: 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.
authors.affiliation: University of Colorado Denver, School of Medicine, Department of Anesthesiology, Aurora, Colorado, USA pierre.moine@ucdenver.edu.
authors.forename: Pierre
authors.initials: P
authors.lastname: Moine
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Mueller
authors.affiliation: University of Colorado Denver, School of Medicine, Department of Surgery, Surgical Weight Loss Center, Aurora, Colorado, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Schoen
authors.affiliation: University of Colorado Denver, School of Medicine, Department of Surgery, Surgical Weight Loss Center, Aurora, Colorado, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Rothchild
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Fish
mesh_terms: D000328:Adult; D019072:Antibiotic Prophylaxis; D001835:Body Weight; D002440:Cefoxitin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D009765:Obesity / Q000601:surgery*; D009767:Obesity, Morbid / Q000601:surgery*; D013530:Surgical Wound Infection / Q000382:microbiology / Q000517:prevention & control*; D014018:Tissue Distribution
chemical_list: D002440:Cefoxitin