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 >40kg/m(2). Ten morbidly obese patients, with a mean [±SD] estimated glomerular filtration rate of 108.4 ± 34.6mL/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 8μg/mL. Mean free cefepime concentrations for t = 30, 120, and 360min were 69.6, 31.6, and 9.2μg/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 10.12h, including time for infusion. There was no toxicity. Based on this analysis, an increased dose of 2g every 8h 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.