Population pharmacokinetics of three alternative prophylactic antibiotics during cardiac surgery with extracorporeal circulation

Abstract

The aim of this pharmacokinetic study was to describe and quantify population pharmacokinetics of three antibiotics, cefazolin, ampicillin, and ciprofloxacin, used as antibacterial prophylaxis during cardiovascular surgery with the use of extracorporeal circulation (ECC). Methods. Adult patients undergoing cardiac surgery with ECC were enrolled to this prospective, pharmacokinetic study. An intravenous bolus of 2 g of ampicillin, 2 g of cefazolin or 400 mg of ciprofloxacin was administered 60-30 min before surgery. Blood samples were collected at 15, 30, 45, 60, 120 and 180 min after the administration and at the end of the surgery. Plasma concentrations of the antibiotics were measured using HPLC methods. Serum concentrationtime profiles were analyzed using nonlinear mixed-effects modeling approach. Results. A total of 54 patients were enrolled into the study, 20 with ampicillin, 25 cefazolin and 9 ciprofloxacin. For all antibiotics, population pharmacokinetic models have been successfully developed. Conclusion.We identified estimated glomerular filtration rate (eGFR) as the main factor determining the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target in ampicillin or cefazolin and body weight in ciprofloxacin prophylaxis during cardiac surgery with ECC support.

Population Pharmacokinetics of Prophylactic Cefazolin in Cardiac Surgery with Standard and Minimally Invasive Extracorporeal Circulation

“…A population pharmacokinetic study by Asada et al revealed decreased cefazolin clearance and an increased volume of distribution during CPB with insufficient probability of target attainment (PTA) for pathogens with MIC > 8 mg/L [ 16 ], which is fortunately not a very common situation in cardiothoracic surgery practice. Cefazolin pharmacokinetics in patients receiving MiECC support was also preliminary explored [ 17 ]; however, differences in the influence of cefazolin pharmacokinetics between ECC and MiECC—if they exist—have not yet been studied using a direct comparison or a comparison with an internal control.…”