Optimizing antimicrobial prophylaxis in reconstructive vascular surgery.
The combinations of cefuroxime and metronidazole, and amoxycillin/clavulanate (Augmentin) are useful as prophylactic drugs during vascular surgery. In this study the pharmacokinetic profiles of different dosing regimens utilizing these drugs during reconstructive vascular procedures are presented. Three groups of patients, undergoing aortobifemoral or femoropopliteal prosthetic surgery, received one of the following regimens: Group I: 1500 mg metronidazole plus 1500 mg cefuroxime at premedication, Group II: 1500 mg metronidazole at premedication plus 1500 mg cefuroxime at the time of induction anaesthesia, followed by 750 mg of cefuroxime 2 h later, Group III: 2000 mg amoxycillin/200 mg clavulanate at time of induction anaesthesia, followed by 1000 mg amoxycillin/200 mg clavulanate, 3 h later. For determination of the antibiotic concentrations, arterial blood samples were obtained at 30-minute intervals during the entire procedure. An additional sample was collected at the time of inguinal graft site anastomosis. Cefuroxime concentrations in these additional samples were 29.3 +/- 11.2 mg/l in group I and 44.7 +/- 15.9 mg/l in group II. Metronidazole concentrations were satisfactorily high in all patients (38.4 +/- 4.5 mg/l). Amoxycillin/clavulanate concentrations were 35.1 +/- 21.5 mg/l and 4.4 +/- 3.7 mg/l respectively. We recommend a multiple dose administration scheme for prophylaxis in high-risk prosthetic vascular surgery, if the procedure takes more than 2-3 h and antimicrobial agents with a rapid elimination time are used. A multiple dosing scheme ensures sufficiently high antibiotic concentrations, exceeding the MIC of staphylococci and enterobacteria approximately twice, at the time of inguinal graft site anastomosis.