From the Journals

Lower C. difficile mortality with vancomycin than metronidazole



Treating Clostridium difficile infection with vancomycin achieves the same recurrence rates as does treatment with metronidazole, but with a significantly lower 30-day mortality, new research suggests.

A retrospective, propensity-matched cohort study examined U.S. Department of Veterans Affairs health care system data from 47,471 patients with C. difficile infection who were treated with either vancomycin or metronidazole, according to a report published online Feb. 6 in JAMA Internal Medicine.

This photograph depicts Clostridium difficile colonies after 48 hours of growth on a blood agar plate; Magnified 4.8X. CDC/D. Holdeman

“Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild to moderate CDI [Clostridium difficile infection],” wrote Vanessa W. Stevens, PhD, of Veterans Affairs Salt Lake City Health Care System, and her coauthors. “Although an early clinical trial found no difference in cure rates between vancomycin hydrochloride and metronidazole, subsequent observational data and clinical trials suggest that metronidazole is inferior to vancomycin for primary clinical cure, especially in severe cases.”

Their study found patients treated with vancomycin had a similar risk of recurrence compared with those treated with metronidazole (relative risk, 0.98; 95% confidence interval, 0.87 to 1.10), with an overall recurrence rate of 16%.

However, patients treated with vancomycin had a 14% reduction in 30-day mortality compared to the metronidazole-treated group. This was after adjustment for factors such as comorbidity scores, hospitalization history, receipt of chemotherapy, receipt of immunosuppressive medication or proton pump inhibitor therapy in the prior 30-days, or antibiotic use on the day of diagnosis.

The 30-day mortality was not significantly different among patients with mild to moderate CDI, but there was a significant 21% reduction among patients with severe infection. The number needed to treat to prevent one death among patients with severe infection was 25 (JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.9045).

“This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and one of the few studies focused on downstream outcomes of CDI,” researchers reported.

The authors noted that despite strong evidence and guidelines supporting the use of vancomycin for severe CDI – and the fact that 42% of episodes in the study were classified as severe – only 4%-6% of patients were prescribed vancomycin.

“Although the excess treatment costs of vancomycin relative to metronidazole and the concern for vancomycin-resistant Enterococcus will likely remain barriers, improved clinical cure and mortality rates may warrant reconsideration of current prescribing practices,” they wrote. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease.”

The study was supported by researcher grants from the U.S. Department of Veterans Affairs. No conflicts of interest were declared.

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