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Updated: Apr 13, 2026

A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment
Published on: May 25, 2017
Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared
Brittany B Lewis1, Charlie G Buffie1, Rebecca A Carter2
1Infectious Disease Service, Department of Medicine Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center.
Abstract:
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.
Insights
Oral vancomycin and metronidazole disrupt the gut microbiota, increasing infection risk. Vancomycin causes prolonged disruption, raising susceptibility to C. difficile and other pathogens.
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Antibiotic use disrupts the gut microbiota, increasing susceptibility to infections like Clostridium difficile.
- Metronidazole and vancomycin are used to treat C. difficile infections.
- The comparative effects of these antibiotics on gut microbiota and colonization resistance are not well understood.
Purpose of the Study:
- To investigate the impact of metronidazole and oral vancomycin on gut microbiota and susceptibility to nosocomial pathogens.
- To compare the effects of metronidazole and vancomycin on colonization resistance in a mouse model.
Main Methods:
- Mice were treated with metronidazole and/or oral vancomycin.
- Susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli was assessed.
- Changes in intestinal microbiota and colonization resistance were evaluated.
Main Results:
- Metronidazole caused a temporary loss of colonization resistance.
- Oral vancomycin led to significant disruption of the microbiota, with prolonged loss of colonization resistance.
- Vancomycin treatment resulted in dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli.
Conclusions:
- Vancomycin and, to a lesser extent, metronidazole significantly disrupt the intestinal microbiota.
- These antibiotic treatments increase the risk of colonization by common hospital-acquired pathogens.
- The findings highlight potential risks associated with using these antibiotics, particularly vancomycin, in high-risk patients.
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