To date only 1 study has attempted to evaluate metronidazole’s role in preventing CDI¹. This work, however,  has significant shortcomings including its retrospective nature, definition of metronidazole prophylaxis as any dose for reasons other than CDI starting 1-3 days before initiation of the primary antibiotic, undefined duration, less comorbidities in the metronidazole group, and surveillance period for CDI limited to only 7 days following initiation of the primary antibiotic. For these reasons, it is difficult to interpret the results of this study whose conclusion was that metronidazole may protective against CDI².

In fact, there are several reasons why metronidazole prophylaxis may not be effective in CDI.   First, due to its very high bioavailability, concentrations of metronidazole in formed stool are often undetectable^2,3 . Consequently, “preventive” metronidazole in patients at risk of CDI but with formed stools would not be expected to achieve high enough concentrations in the colon to be effective.  In additions, metronidazole itself may be associated with CDI⁴ and  vancomycin-resistant enterococci⁵,  and has several potential drug-interactions and adverse effects⁶ .

References

1. Rodriguez S, Hernandez MB, Tarchini G, et al. Risk of Clostridium difficile infection in hospitalized patients receiving metronidazole for a non-C difficile infection. Clin Gastroenterol Hepatol 2014;12:1856-61. https://www.ncbi.nlm.nih.gov/pubmed/24681079
2. Dupont HL. Chemoprophylaxis of Clostridium difficile infections in high-risk hospitalized patients. Clin Gastroenterol Hepatol 2014;12: 1862-63. https://www.ncbi.nlm.nih.gov/labs/articles/24768812/
3. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut 1986;27:1169-1172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1433873/pdf/gut00370-0065.pdf
4. Daly JJ, Chowdary KV. Pseudomembranous colitis secondary to metronidazole. Dig Dis Sci 1983;28:573-4.
5.  Carmeli Y, Eliopoulos GM, Samore MH. Antecedent treatment with different antibiotic agents as a risk factor for vancomycin-resistant enterococcus. Emerg Infect Dis 2002;8:802-807. https://wwwnc.cdc.gov/eid/article/8/8/pdfs/01-0418.pdf
6. Salvatore M, Meyers BR. Metronidazole. In Mandel, Douglas, Bennett’s Principles and Practice of Infectious Diseases-7^th Ed. p. 419-426. 2010, Churchill Livingstone, Philadelphia.