Imipenem concentrations in colorectal surgery and impact on the colonic microflora

Abstract

Twenty patients undergoing colorectal surgery were given, as prophylaxis, imipenem-cilastatin intravenously. Ten of them received a dose of 0.5/0.5 g of imipenem-cilastatin at induction of anesthesia, followed by subsequent doses of 0.5/0.5 g every 6 h for 48 h. The other 10 patients were given 1.0/1.0 g imipenem-cilastatin in the same way for 48 h. Samples from serum, intestinal mucosa, and feces were taken for analysis of imipenem concentrations during the day of surgery. The mean concentrations in serum at 1 h after the first imipenem dose were 15.9 +/- 1.7 micrograms/ml for the 0.5-g dose and 68.2 +/- 8.2 micrograms/ml for the 1.0-g dose. The mean half-lives were 1.5 and 1.4 h, respectively, and the mean areas under the serum concentration-time curve were 41.2 +/- 6.0 and 128.3 +/- 13.5 mg.h/liter, respectively. The imipenem concentrations in the intestinal mucosa varied between less than 0.1 and 3.6 mg/kg for the 0.5-g dose and 3.2 and 13.4 mg/kg for the 1.0-g dose. The concentrations in the fecal samples varied between less than 0.1 and 5.0 mg/kg for the 0.5-g dose and 0.7 and 11.3 mg/kg for the 1.0-g dose. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. The aerobic bacteria--staphylococci, streptococci, enterococci, and enteroaerobic enterococci, and enterobacteria--were and anaerobic bacteria. The aerobic bacteria--staphylococci, streptococci, enterococci, and enterobacteria--were suppressed significantly during the imipenem prophylaxis period. Among the anaerobic bacteria, cocci, bifidobacteria, eubacteria, lactobacilli, clostridia, fusobacteria, and bacteroides decreased markedly during the same period. The microfloras were normalized after 2 weeks. There were no differences between the patients receiving 0.5-g doses of imipenem and those receiving 1.0-g of imipenem. No postoperative infections occurred.