title: The complex dynamics of antimicrobial activity in the human gastrointestinal tract.
abstract: The human gastrointestinal tract is a complex environment of mutualistic associations. As bacteria form a major component of fecal content, the natural balance of the colon can be significantly altered by exposure to antimicrobial agents. However, the effects of antimicrobial therapy on fecal content are difficult to predict and can at times be quite surprising. The emergence and spread of vancomycin-resistant enterococci are cases in point. Resistance to the glycopeptide vancomycin emerged in enterococci (primarily in Enterococcus faecium) in the late 1980s in both Europe and the United States. In Europe, this emergence was tied to the use of the glycopeptide antibiotic avoparcin to promote growth in food animals and had little actual impact on hospital infections. In the United States, where avoparcin has never been licensed, vancomycin-resistant enterococci (VRE) emerged as a major hospital pathogen. Paradoxically, while the initial entry of the vancomycin resistance determinants into enterococci was almost certainly driven by high fecal concentrations of vancomycin associated with treatment for Clostridium difficile colitis, clinical infection and outbreaks were more frequently tied to use of extended-spectrum cephalosporins and agents with potent activity against anaerobic bacteria. Animal studies suggest that cephalosporins promote initial VRE colonization because of the frequent concomitant high-level resistance to β-lactam antibiotics expressed by these strains. Anti-anaerobic agents appear to increase the output of VRE in the feces, presumably by reducing the number of competitive flora in the colon. Intravenously administered vancomycin appears to have little impact because it achieves negligible concentrations in the feces after short courses. Thus, the spread of glycopeptide resistance in enterococci is promoted in a large measure by the administration of non-glycopeptide antibiotics.
authors.affiliation: Department of Medicine, RhodeIsland Hospital, 593 Eddy Street, Providence, RI 02906, USA. lrice@lifespan.org
authors.forename: Louis B
authors.initials: LB
authors.lastname: Rice
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016983:Enterococcus / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin