Is antibiotic penetration compromised in the ischaemic tissues of patients undergoing amputation?

Antibiotic prophylaxis is indicated for patients undergoing amputation for severe ischaemia or gangrene. However, the adequacy of tissue levels of antibiotics in ischaemic tissue is not known. In this study the serum and tissue antibiotic levels were measured after intravenous administration of metronidazole (15 mg/kg body weight) and cephradine (20 mg/kg body weight). In 11 patients, venous samples were taken at time 0 (induction of anaesthesia) 10, 30 and 60 min. Samples of 2 g each of fat and muscle were collected from the amputation site and three distal sites. Metronidazole and cephradine levels were measured and the degree of limb ischaemia estimated preoperatively by an isotope limb blood flow method. Our results indicate that both metronidazole and cephradine penetrate ischaemic tissues to levels equivalent of a Mean Inhibitory Concentration (MIC) 50 for most organisms encountered in vascular surgery, and that the degree of ischaemia does not alter this.