INADEQUATE LEVELS OF METRONIDAZOLE IN SUBCUTANEOUS FAT AFTER STANDARDPROPHYLAXIS

The efficacy of antibiotic prophylaxis depends on appropriate tissue l evels of the drug being present at the time of potential wound contami nation. Metronidazole concentrations in serum, muscle and subcutaneous fat were measured after a single intravenous dose given at two differ ent intervals before operation. Twenty-six patients undergoing abdomin al wall procedures were divided into two groups. Patients in group 1 r eceived metronidazole 500 mg intravenously 2 h before surgery, and tho se in group 2 were given the drug during induction of anaesthesia. Mea n plasma levels of metronidazole at the beginning of the procedure wer e significantly lower (P = 0.01) in group 1 (7.3 (95 per cent confiden ce interval 5.7-8.9)) mu g/ml than in group 2 (12.3 (8.9-15.7)) mu g/m l although in both cases were above the minimum inhibitory concentrati on for 90 per cent of Bacteroides fragilis. Similar therapeutic concen trations of metronidazole were achieved in plasma and muscle in both g roups at the end of the operation. However, patients in both groups ha d non-therapeutic concentrations of metronidazole in subcutaneous fat: group 1 0.9 (0.6-1.2) mu g/mg, group 2 1.2 (0.7-1.7) mu g/mg at the b eginning of operation, and 1.2 (0.8-1.6) and 1.5 (0.9-2.1) mu g/mg res pectively at the end of the procedure. It is concluded that infusion o f metronidazole 2 h before surgery or during induction of anaesthesia achieved adequate plasma and muscle levels but failed to achieve thera peutic levels in subcutaneous fat.