Increased 3-gram cefazolin dosing for cesarean delivery prophylaxis in obese women

Abstract

The purpose of this study was to determine tissue concentrations of cefazolin after the administration of a 3-g prophylactic dose for cesarean delivery in obese women (body mass index [BMI] >30 kg/m(2)) and to compare these data with data for historic control subjects who received 2-g doses. Acceptable coverage was defined as the ability to reach the minimal inhibitory concentration (MIC) of 8 μg/mL for cefazolin. We conducted a 2-phase investigation. The current phase is a prospective cohort study of the effects of obesity on tissue concentrations after prophylactic 3-g cefazolin doses at the time of cesarean delivery. Concentration data after 3-g were compared with data for historic control subjects who had received 2-g. Three grams of parenteral cefazolin was given 30-60 minutes before skin incision. Adipose samples were collected at both skin incision and closure. Cefazolin concentrations were determined with the use of a validated high-performance liquid chromatography assay. Twenty-eight obese women were enrolled in the current study; 29 women were enrolled in the historic cohort. BMI had a proportionally inverse relationship on antibiotic concentrations. An increase of the cefazolin dose dampened this effect and improved the probability of reaching the recommended MIC of ≥8 μg/mL. Subjects with a BMI of 30-40 kg/m(2) had a median concentration of 6.5 μg/g (interquartile range [IQR], 4.18-7.18) after receiving 2-g vs 22.4 μg/g (IQR, 20.29-34.36) after receiving 3-g. Women with a BMI of >40 kg/m(2) had a median concentration of 4.7 μg/g (IQR, 3.11-4.97) and 9.6 μg/g (IQR, 7.62-15.82) after receiving 2- and 3-g, respectively. With 2 g of cefazolin, only 20% of the cohort with a BMI of 30-40 kg/m(2) and none of the cohort with a BMI of >40 kg/m(2) reached an MIC of ≥8 μg/mL. With 3-g, all women with a BMI of 30-40 kg/m(2) reached target MIC values; 71% of the women with a BMI of >40 kg/m(2) attained this cutoff. Higher adipose concentrations of cefazolin were observed after the administration of an increased prophylactic dose. This concentration-based pharmacology study supports the use of 3 g of cefazolin at the time of cesarean delivery in obese women. Normal and overweight women (BMI <30 kg/m(2)) reach adequate cefazolin concentrations with the standard 2-g dosing.