Inadequate levels of metronidazole in subcutaneous fat after standard prophylaxis.

The efficacy of antibiotic prophylaxis depends on appropriate tissue levels of the drug being present at the time of potential wound contamination. Metronidazole concentrations in serum, muscle and subcutaneous fat were measured after a single intravenous dose given at two different intervals before operation. Twenty-six patients undergoing abdominal wall procedures were divided into two groups. Patients in group 1 received metronidazole 500 mg intravenously 2 h before surgery, and those in group 2 were given the drug during induction of anaesthesia. Mean plasma levels of metronidazole at the beginning of the procedure were significantly lower (P = 0.01) in group 1 (7.3 (95 per cent confidence interval 5.7-8.9)) micrograms/ml than in group 2 (12.3 (8.9-15.7)) micrograms/ml although in both cases were above the minimum inhibitory concentration for 90 per cent of Bacteroides fragilis. Similar therapeutic concentrations of metronidazole were achieved in plasma and muscle in both groups at the end of the operation. However, patients in both groups had non-therapeutic concentrations of metronidazole in subcutaneous fat: group 1 0.9 (0.6-1.2) micrograms/mg, group 2 1.2 (0.7-1.7) micrograms/mg at the beginning of operation, and 1.2 (0.8-1.6) and 1.5 (0.9-2.1) micrograms/mg respectively at the end of the procedure. It is concluded that infusion of metronidazole 2 h before surgery or during induction of anaesthesia achieved adequate plasma and muscle levels but failed to achieve therapeutic levels in subcutaneous fat.