BASIC STUDY ON THE USE OF ANTIMICROBIAL AGENTS FOR PREVENTING INFECTION FOLLOWING COLON SURGERY

Abstract

Based on clinical findings and animal studies showing changes in intestinal bacterial flora in rats, we have previously reported the usefulness of colon preparation for preventing postoperative infection in colon surgery. In this study, we selected effective microbial agents forcolon preparation before surgery, and determined adequate dosages and treatment duration from a new point of view, namely, in addition to performing a basic study on changes in major intestinal bacterial flora, we serially measured levels of various antimicrobial agents in intestinal contents in normal rats fed with elemental diet and in rats with a stenosis prepared as an ileus model. In the normal rats, metronidazole (MTN) when given orally together with kanamycin (KM) for 4 consecutive dayswas first detected in intestinal contents on daytreatment, and its levels in the cecum andrectum were 9.0 and 3.5 μg/g. This concomitant treatment markedly reduced major intestinal flora. When the animals were percutaneously treated with piperacillin (PIPC), cefmetazole (CMZ), cefoperazone (CPZ), or cefoperazone (CPZ) +sulbactam (SBT), peak levels appeared 8 h in the cecum and 24h in the rectum after administration of PIPC, and the other agents peaked 24 h after administration. Peak levels in the cecum and rectum were 430 and 141 μg/g of PIPC, 753 and 1, 025 peg of CMZ, 66 and 978 μg/g of CPZ, and 89 and 790 μg/g of SBT. When levels peaked intestinal bacterial flora in the groups percutaneously treated with CMZ and CPZ+SBT showed the same effect as that in the group given KM+MTN orally. In the rats with stenosis prepared as a model of patients without sufficient preoperative preparation, including oral treatment with antimicrobial agents, due to an occlusive condition, the levels of penetration of CMZ and CPZ+SBT were determined because these agents were thought to sufficiently penetrate into intestinal contents in the normal rats. Although CMZ and CPZ+SBT peaked only 36 h after administration, the decrease in intestinal bacterial flora was the same as that seen in the normal rats. These results suggest that oral treatment with KM+ MTN for 4 consecutive days, and percutaneous treatment with CMZ or CPZ+SBT at 24 h before operation serve as an effective preoperative colon preparation to prevent infection following colon surgery, and that systemic treatment with CMZ or CPZ+ SBT 36 h before operation is an effective bacteriological preparation, even if an occlusive condition prevents mechanical preparation.