Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole

J Infect Dis. 2015 Nov 15;212(10):1656-65. doi: 10.1093/infdis/jiv256. Epub 2015 Apr 28.


Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens.

Keywords: Clostridium difficile; colonization resistance; metronidazole; microbiota; vancomycin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / administration & dosage*
  • Anti-Infective Agents / adverse effects
  • Bacterial Infections / immunology*
  • Bacterial Infections / microbiology
  • Clostridioides difficile / isolation & purification
  • Disease Models, Animal
  • Disease Resistance / drug effects*
  • Escherichia coli / isolation & purification
  • Female
  • Klebsiella pneumoniae / isolation & purification
  • Metronidazole / administration & dosage*
  • Metronidazole / adverse effects
  • Mice, Inbred C57BL
  • Vancomycin / administration & dosage*
  • Vancomycin / adverse effects
  • Vancomycin-Resistant Enterococci / isolation & purification


  • Anti-Infective Agents
  • Metronidazole
  • Vancomycin