Pharmacokinetic characteristics and microbiologic appropriateness of cefazolin for perioperative antibiotic prophylaxis in elective cardiac surgery

Abstract Objective Adequate levels of perioperative antibiotic prophylaxis are essential for prevention of surgical site infections. We examined pharmacokinetic details of 2 g cefazolin administered during induction of anesthesia with repeat dosing shortly after initiation of cardiopulmonary bypass (CPB) in cardiac surgery. Methods To identify the microbiologic flora targeted with prophylaxis, pre-, and postoperative swabs were taken from sternal skin. Blood samples for measurement of cefazolin were obtained in 24 patients. Drug levels were used for population pharmacokinetic modeling using Nonmem software (Icon Development Solutions, San Antonio, Tex). Results More than 90% of bacteria on sternal skin were sensitive to cefazolin, indicating minimal inhibitory concentrations d ) of 15.8 L. CPB increased V d from 14.4 L to 22.1 L with a consecutive reduction to 18 L after the end of extracorporeal circulation. The final model implemented interindividual variability on CL and V d , incorporating the covariates CPB and albumin on V d and creatinine clearance on CL. Goodness-of-fit calculations showed that this model adequately describes the data derived from our clinical cohort. Conclusions Two grams of cefazolin at induction of anesthesia with a repeat dose after initiation of CPB ensures adequate drug levels to target a majority of pathogens of surgical site infections. Pharmacokinetic modeling demonstrated a significant influence of CPB on the volume of distribution and elimination of cefazolin. Other influences on pharmacokinetic parameters were albumin, protein, and creatinine clearance.