Suppression of colonic microflora by cefoperazone and evaluation of the drug as potential prophylaxis in bowel surgery

Abstract

We evaluated the activity of cefoperazone (CPZ) on the intestinal flora in terms of its use as a single prophylactic drug in colon surgery. Twenty-four healthy male volunteers between the ages of 20 and 40 were assigned to receive either CPZ, oral neomycin-erythromycin, or no antibiotics. A mechanical bowel preparation, Golytely, was also given to each of the subjects. With intravenous CPZ, antibiotic levels in the stool ranged from <2 to 649 ,ug/ml and the total fecal bacterial counts dropped 3 to 4 log1o CFU/g. Higher levels of CPZ were detected in the stools when an oral dose was added, 1,446 to 5,445 ,ug/ml, and the bacterial counts were reduced maximally 4 to 6 loglo CFU/g. The combination of the oral and intravenous doses produced suppression of the microflora and high levels in blood, all with a single antibiotic.The most widely accepted form of antimicrobial prophylaxis for elective colorectal surgery in the United States is the combination of oral neomycin-erythromycin in a threedose schedule, administered at 1, 2, and 11 p.m. the day before surgery (16). It is becoming commonplace to combine this oral regimen with a parenteral cephalosporin antibiotic in order to provide levels of antibiotic in blood and enhance systemic protection. Some studies have suggested that the third drug, usually a cephalosporin with activity against Bacteroides fragilis, provides protection superior to that provided by the oral drugs alone (6, 18). This point remains controversial, however, because postoperative infection rates in the groups receiving the oral preparation alone are usually higher (-15%) than those reported in the earlier large-scale Veterans Administration cooperative studies that established the efficacy of the neomycin-erythromycin preparation (6 to 9%) (5).The rationale for the oral antibiotic bowel preparation is suppression of the intestinal microflora so that any leakage of luminal contents would contain a low inoculum of microorganisms (19). The parenteral antibiotic is thought to add another barrier to tissue invasion by organisms in the microflora by creating a level of antibiotic in blood.In addition to the antimicrobial regimen, mechanical cleansing is of fundamental importance in reducing the bacterial burden. However, in patients who are operated on urgently or who have bowel obstruction, it may not be possible to effect mechanical cleansing or to administer an oral regimen, and the main burden for prophylaxis in these high-risk patients falls upon the parenterally administered drug(s). Despite the preliminary evidence that there is a benefit from concomitant oral and parenteral antibiotics in prophylaxis for bowel surgery, there are clear concerns about such an approach from the aspects of drug toxicity, antibiotic resistance, and cost (19). Thus, there would be considerable interest in a regimen which meets the same objectives with a single drug. MATERIALS AND METHODSSubjects. Twenty-four healthy males, ages 20 to 40 years, were studied. They underwent a complete physical examination and routin...

Antibiotic-Associated Diarrhea and Pseudomembranous Colitis: Are They Less Common with Poorly Absorbed Antimicrobials?

“…Antibiotics with less anaerobic suppression (tetracycline, penicillin) appear to have a lower risk of CDAD. In one study, a cephalosporin given intravenously showed minimal anaerobic suppression; this increased when given orally [43].…”

Evaluation of New Anti-Infective Drugs for Surgical Prophylaxis

“…Furthermore, it can be combined effectively with an oral antibiotic regimen given in the afternoon and evening before the planned operation the next morning. When given with the neomycin-erythromycin preparation, isotonic lavage achieves remarkable suppression of the aerobic and anaerobic flora; however, the lavage preparation alone, without antibiotics, fails to suppress the flora adequately [47].…”