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

Background: 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. Methods: Twenty obese patients (first trimester body mass index [BMI] >35) who underwent cesarean delivery completed this randomized study. Eleven patients received 2g of cefazolin, and nine received 4g. 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 4mcg/g for tissue samples was used as a surrogate adequate concentration. Plasma and tissue cefazolin concentrations were compared for the two doses. Results: 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 (40.1124.10mcg/g vs. 18.36 +/- 6.68mcg/g; p=0.0005). Subcutaneous tissue concentrations at closure were significantly different in the two dosage groups (34.89 +/- 17.42mcg/g vs. 21.73 +/- 16.02mcg/g; p=0.044). All tissue samples were above the target of 4mcg/g. Body morphometry did not correlate with the variability in cefazolin tissue concentration. No surgical site infections, endometritis, or other adverse effects were observed. Conclusions: Administering a prophylactic dose of 4g 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 60kg/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.