Plasma and Tissue Cefazolin Concentrations in Obese Patients Undergoing Cesarean Delivery and Receiving Differing Pre-Operative Doses of Drug

Abstract

Patients undergoing cesarean delivery typically receive a 1-g to 2-g dose of cefazolin as pre-operative antibacterial prophylaxis. This traditional dosage may not provide an adequate tissue concentration of cefazolin in obese patients during the peri-operative period. This study compared the tissue concentrations of prophylactic cefazolin administered as a either a 2-g or a 4-g dose prior to cesarean delivery in obese patients. Twenty obese patients (first trimester body mass index [BMI] >35) who underwent cesarean delivery completed this randomized study. Eleven patients received 2 g of cefazolin, and nine received 4 g. Blood and subcutaneous tissues were collected at the times of the incision and closure. Myometrial biopsies were collected at uterine closure. A cefazolin concentration threshold of 4 mcg/g for tissue samples was used as a surrogate adequate concentration. Plasma and tissue cefazolin concentrations were compared for the two doses. Mean plasma, umbilical cord, and myometrial cefazolin concentrations were significantly higher in the 4-g treatment group (p<0.05). Subcutaneous incision site tissue obtained at time of incision creation also was significantly higher in the 4-g group than in the 2-g group (40.11±24.10 mcg/g vs. 18.36±6.68 mcg/g; p=0.0005). Subcutaneous tissue concentrations at closure were significantly different in the two dosage groups (34.89±17.42 mcg/g vs. 21.73±16.02 mcg/g; p=0.044). All tissue samples were above the target of 4 mcg/g. Body morphometry did not correlate with the variability in cefazolin tissue concentration. No surgical site infections, endometritis, or other adverse effects were observed. Administering a prophylactic dose of 4 g of cefazolin produced blood and tissue cefazolin concentrations that were significantly higher than concentrations obtained from a 2-g dose in patients with BMIs between 35 and 60 kg/m(2) undergoing cesarean delivery. It is unclear if the larger cefazolin dose produces a more protective anti-infective effect than that obtained with the more traditional 2-g dose for cesarean delivery in obese patients.