title: The significance of timing of metronidazole prophylaxis and addition of fosfomycin in colorectal surgery. An experimental study in rats.
abstract: A novel approach to antibiotic prophylaxis in colonic surgery, suggested by our previous clinical experience, was experimentally tested. Intravenous administration of metronidazole or fosfomycin at greater than or equal to 4 hours before surgery effectively prevented lethal infectious complications, whereas metronidazole prophylaxis begun at induction of anaesthesia proved to be much less efficacious (4% and 43% deaths vs. 50% among controls, p less than 0.001 and p greater than 0.7, respectively). The in vivo efficacy of antibiotic prophylaxis correlated better with mucosal counts of Clostridium and Bacteroides than with luminal counts of aerobic or anaerobic bacteria. Earlier initiation of intravenous metronidazole prophylaxis thus markedly increased its in vivo efficacy, apparently due to preoperative mucosal suppression of endogenous potential pathogens. This 'early timing' approach to systemic prophylaxis against infection in abdominal surgery warrants further evaluation both for other antibiotics and clinically.
authors.affiliation: Department of Surgery, Umeå University, Stockholm, Sweden.
authors.forename: P A
authors.initials: PA
authors.lastname: Kling
authors.forename: C E
authors.initials: CE
authors.lastname: Nord
authors.forename: L G
authors.initials: LG
authors.lastname: Burman
mesh_terms: D000818:Animals; D003106:Colon / Q000382:microbiology; D003108:Colonic Diseases / Q000601:surgery*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D012002:Rectal Diseases / Q000601:surgery*; D013530:Surgical Wound Infection / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D008795:Metronidazole