Study Compares Two Antibiotics For the Treatment of Clostridium difficile

According to a new study, the antibiotic vancomycin was as effective at treating severe cases of Clostridium difficile infections as metronidazole, but more effective at reducing the risk of morality, justifying its use as initial therapy for severe C. difficile.

Metronidazole hydrochloride has historically be considered the first-line therapy for patients with mild to moderate C. difficile, but is inferior to vancomycin hydrochloride for clinical cure.
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In order to evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving either vancomycin or metronidazole, researchers conducted a retrospective, propensity-matched cohort study using data from the US Department of Veteran Affairs healthcare system from January 1, 2005 to December 31, 2012. The study included 47,471 patients identified with C. difficile, 1947 of whom were women and 45,524 were men, mean age 68.8 years.

All-cause mortality within 30 days after the initial C. difficile diagnosis, and recurrence of the infection within 8 weeks after the initial diagnosis were compared.

A total of 2068 patients were treated with vancomycin, and the patients were matched with 8069 patients treated with metronidazole. Subcohorts included 5452 patients with mild to moderate C. difficile and 3130 patients with severe C. difficile infections. Vancomycin was used to treat 1112 patients with mild to moderate C. difficile, 620 with severe C. difficile, 326 with unknown severity. The remaining patients received metronidazole.

No differences in the risk of recurrence was found between patients treated with vancomycin and patients treated with metronidazole, regardless of severity.

“We observed that patients with severe [C. difficile infection] treated with vancomycin were approximately 20% less likely to die of any cause within 30 days than patients treated with metronidazole. This [relative risk] reduction translates to an absolute risk reduction of 4% (95% CI, 1%-7%). Conversely, there was no difference in the risk of 30-day mortality between vancomycin and metronidazole among patients with mild to moderate [C. difficile infection],” the researchers wrote. 

They recommend physicians reconsider their prescribing practices, particularly for patients with severe C. difficile infections, and for further research to consider the economic and vancomycin-resistant Enterococcus that limit the use of vancomycin for treating C. difficile.

—Melissa Weiss

Reference:

Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficle infection [published online February 6, 2017]. JAMA Internal Medicine. doi: 10.1001/jamainternmed.2016.9045.