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Erikstrup LT, Aarup M, Hagemann-Madsen R, et al. Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination. BMJ Open Gastroenterol. 2015;2(1):e000038doi: 10.1136/bmjgast-2015-000038.
Erikstrup, L. T., Aarup, M., Hagemann-Madsen, R., Dagnaes-Hansen, F., Kristensen, B., Olsen, K. E., & Fuursted, K. (2015). Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination. BMJ open gastroenterology, 2(1), e000038. https://doi.org/10.1136/bmjgast-2015-000038
Erikstrup, Lise Tornvig, et al. "Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination." BMJ open gastroenterology vol. 2,1 (2015): e000038. doi: https://doi.org/10.1136/bmjgast-2015-000038
Erikstrup LT, Aarup M, Hagemann-Madsen R, Dagnaes-Hansen F, Kristensen B, Olsen KE, Fuursted K. Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination. BMJ Open Gastroenterol. 2015 Nov 02;2(1):e000038. doi: 10.1136/bmjgast-2015-000038. eCollection 2015. PMID: 26568840; PMCID: PMC4641438.
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BMJ Open Gastroenterol. 2015 Nov 02;2(1):e000038. doi: 10.1136/bmjgast-2015-000038. eCollection 2015.

Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination.

BMJ open gastroenterology

Lise Tornvig Erikstrup, Mie Aarup, Rikke Hagemann-Madsen, Frederik Dagnaes-Hansen, Brian Kristensen, Katharina Elisabeth Pribil Olsen, Kurt Fuursted

Affiliations

  1. Department of Clinical Microbiology , Aarhus University Hospital , Aarhus , Denmark ; Institute of Clinical Medicine, Aarhus University , Aarhus , Denmark.
  2. Department of Clinical Microbiology , Aarhus University Hospital , Aarhus , Denmark ; Department of Biomedicine , Aarhus University , Aarhus , Denmark.
  3. Department of Clinical Pathology , Vejle Hospital , Vejle , Denmark.
  4. Department of Biomedicine , Aarhus University , Aarhus , Denmark.
  5. Department of Microbiology and Infection Control , Statens Serum Institute , Copenhagen , Denmark.

PMID: 26568840 PMCID: PMC4641438 DOI: 10.1136/bmjgast-2015-000038

Abstract

OBJECTIVE: Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone.

DESIGN: C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline by oral gavage. After the challenge, the mice were treated with placebo, vancomycin, metronidazole or a combination of vancomycin and metronidazole for 10 days. The mice were monitored for 20 days with weight and a clinical score. Stool samples were examined for C. difficile spore load and presence of C. difficile toxins.

RESULTS: None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole recovered from CDI faster than mice treated with metronidazole alone. However, after discontinuation of treatment, vancomycin-treated and combination-treated mice succumbed to clinical and bacteriological relapse.

CONCLUSIONS: Mice treated with vancomycin alone had a better clinical outcome in the treatment phase of CDI than mice treated with metronidazole alone. A combination of vancomycin and metronidazole did not improve the clinical outcome when compared to treatment with vancomycin alone.

TRIAL REGISTRATION NUMBER: The trial registration number from the Danish Experimental Animal Inspectorate is J number 2012-15-2934-00422.

Keywords: ANTIBIOTIC THERAPY; BACTERIAL INFECTION; COLONIC BACTERIA; COLONIC DISEASES; INFECTIOUS DIARRHOEA

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