Concentrations of ampicillin plus sulbactam in serum and intestinal mucosa and effects on the colonic microflora in patients undergoing colorectal surgery.

Ampicillin and sulbactam were administered intravenously in 2 g and 1 g doses respectively every 8 h for two days to ten patients undergoing colorectal surgery. Drug concentrations were determined in serum, intestinal mucosa and faeces. The first dose was given at induction of anesthesia. The serum half-life was 2.1 h for ampicillin and 2.0 h for sulbactam on the first day. The concentrations in intestinal mucosa were in most cases 50% or more of the serum concentrations and there was no statistical difference between the two drugs. Faecal concentrations of both drugs were found in eight patients: a mean of 10.5 micrograms/g for ampicillin and a mean of 7.5 micrograms/g for sulbactam. Faecal samples were also collected during the investigation period for culture of aerobic and anaerobic bacteria. Among the aerobic bacteria enterococci, streptococci and enterobacteria decreased markedly during the prophylaxis period. Anaerobic bacteria were also suppressed significantly during the same period. The changes in colonic microflora were related to the concentrations of ampicillin and sulbactam in the intestinal mucosa and faeces. Overgrowth of yeasts was observed in six patients and overgrowth of Pseudomonas fluorescens in two others. These strains were resistant to the combination ampicillin and sulbactam. The microflora normalized in all patients after two weeks. No postoperative infections occurred.