Vancomycin may have mortality benefit over metronidazole for patients with severe C. difficile, study finds

The retrospective study found no statistically or clinically significant differences in recurrence rates between patients receiving vancomycin and metronidazole regardless of the severity of Clostridium difficile infection.


Patients with severe Clostridium difficile infection who were treated with vancomycin experienced lower mortality risks than those treated with metronidazole, a recent study showed.

Researchers retrospectively compared the effectiveness of the two antibiotics using data from patients treated for C. difficile infection in outpatient, inpatient, or long-term care settings within the U.S. Department of Veterans Affairs health care system from 2005 to 2012. The primary outcomes were recurrent C. difficile infection (another positive laboratory test result more than two weeks but fewer than eight weeks after initial diagnosis) and all-cause mortality within 30 days of diagnosis.

A total of 47,471 patients (mean age, 68.8 years; 4.1% female) were eligible for the study, and 2,068 patients (4.4%) received vancomycin as initial therapy. After propensity matching, researchers compared differences among 10,137 patients with C. difficile infection of any severity (unknown, mild to moderate, or severe); 2,068 were treated with vancomycin, and 8,069 matched patients were treated with metronidazole. A total of 5,452 patients had mild to moderate C. difficile infection, and 3,130 patients had severe infection, as defined by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (SHEA/IDSA) joint practice guidelines. Study results were published online on Feb. 6 by JAMA Internal Medicine.

There were no statistically or clinically significant differences in recurrence rates between patients receiving vancomycin and metronidazole across all severity groups. However, patients who received vancomycin had a lower risk of mortality than those who received metronidazole (8.6% vs. 10.6%; P=0.01), a difference driven largely by the reduction in patients with severe infection (15.3% on vancomycin vs. 19.8% on metronidazole; P=0.01). There was no significant difference in mortality risk among patients with mild to moderate infection (5.9% on vancomycin vs. 6.9% on metronidazole; P=0.22). Among patients with severe infection, the number needed to treat with vancomycin to prevent one death was about 25.

SHEA/IDSA clinical practice guidelines support metronidazole for mild to moderate C. difficile infection and vancomycin for severe C. difficile infection, the authors noted. Although vancomycin use increased during the study period, half of patients with severe infection still did not receive vancomycin in 2012, they found.

Improved mortality rates with vancomycin may warrant consideration of changing prescribing practices, but barriers include its higher costs relative to metronidazole and concerns about vancomycin-resistant Enterococcus, they added. “One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease,” they suggested. Limitations of the study include its observational design, the possibility of unmeasured confounding, and potential changes in treatment that may not have been captured in the initial treatment window.