title: Cefepime dosing in the morbidly obese patient population.
abstract: Proper dosing of specific antibiotics in morbidly obese patients has been studied inadequately. However, these data are beneficial as this patient population is at an increased risk to develop postoperative infections. Cefepime is an antibiotic used for the treatment of both gram-positive and especially gram-negative infections; administration of the appropriate dose in the morbidly obese population is crucial. We therefore examined the pharmacokinetics of cefepime in patients with body mass index >40 kg/m(2). Ten morbidly obese patients, with a mean [±SD] estimated glomerular filtration rate of 108.4 ± 34.6 mL/min, undergoing elective weight loss surgical procedures were administered cefepime in addition to standard prophylactic cefazolin and studied. Serial serum cefepime concentrations were analyzed after dosing using a validated high performance liquid chromatography method. Pharmacokinetics and duration above the minimum inhibitory concentration (MIC) were determined using a protein binding value of 15% and a MIC threshold of 8 μg/mL. Mean free cefepime concentrations for t = 30, 120, and 360 min were 69.6, 31.6, and 9.2 μg/mL, respectively. The dosing interval was calculated to maintain the free concentration above the MIC (fT > MIC) for 60% of the interval. This was determined to be 10.12 h, including time for infusion. There was no toxicity. Based on this analysis, an increased dose of 2 g every 8 h is necessary to maintain an adequate fT > MIC throughout the dosing interval. Further studies are necessary to determine the efficacy of this regimen in the settings of active infections and critical illness.
authors.affiliation: Department of Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, 525 East 68 Street, Box 207, New York, NY 10065, USA. barrie.rich@gmail.com
authors.forename: Barrie S
authors.initials: BS
authors.lastname: Rich
authors.forename: Rebecca
authors.initials: R
authors.lastname: Keel
authors.forename: Vanessa P
authors.initials: VP
authors.lastname: Ho
authors.forename: Harma
authors.initials: H
authors.lastname: Turbendian
authors.forename: Cheguevara I
authors.initials: CI
authors.lastname: Afaneh
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Dakin
authors.forename: Alfons
authors.initials: A
authors.lastname: Pomp
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
authors.forename: Philip S
authors.initials: PS
authors.lastname: Barie
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D013530:Surgical Wound Infection / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime