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Vancomycin significantly reduces mortality risk in severe C. difficile infections

Vancomycin should be considered as the first-line therapy for patients with severe Clostridium difficile infection rather than routinely prescribed metronidazole, according to research published in JAMA Internal Medicine.

“During the past 2 decades, Clostridium difficile infection (CDI) has progressed from a relatively uncommon hospital-acquired infection to a major contributor to morbidity and mortality inside and outside the hospital,” Vanessa W. Stevens, PhD, from the Veterans Affairs Salt Lake City Health Care System, and colleagues wrote. “Current guidelines recommend metronidazole hydrochloride as initial therapy for most cases of mild-to-moderate CDI. 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.”

However, Stevens and colleagues noted that outcomes such as recurrence and all-cause 30-day mortality have been less studied, so they sought to enhance existing evidence by assessing these outcomes among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI. The researchers used data from the U.S. Department of Veterans Affairs health care system to identify patients treated for CDI between Jan. 1, 2005 and Dec. 31, 2012 (n = 47,471; mean age, 68.8 years; 1,947 women [4.1%]; 45,524 men [95.9%]). They defined recurrence as a second positive test within the first 8 weeks of CDI diagnosis and all-cause 30-day mortality as death from any cause within the first 30 days of CDI diagnosis.

Approximately 4% (n = 2,068) of the 47,471 patients who met the study criteria were treated with vancomycin. Those patients were propensity-matched to 8,069 patients who were treated with metronidazole, totaling 10,137 included patients. The investigators categorized patients into two subcohorts based on severity of disease: mild-to-moderate (n = 5,452) and severe (n = 3,130).

Results showed no difference between patients in either treatment group or severity subgroup in recurrence. Patients in the vancomycin group in either severity cohort had lower mortality rates than those in the metronidazole group (adjusted RR = 0.86; 95% CI, 0.74-0.98; adjusted risk difference, –0.02; 95% CI, –0.03 to –0.01). There was no significant difference in mortality risk between patients with mild-to-moderate CDI treated with either vancomycin or metronidazole; however, in patients with severe CDI treated with vancomycin, there was a significant reduction in the risk for all-cause 30-day mortality.

“Our results build on existing evidence that vancomycin may be preferable to metronidazole, particularly for patients with severe disease,” Stevens and colleagues concluded. “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. One approach to minimizing the effects of increasing vancomycin use is to target vancomycin treatment to patients with severe disease. Future research should focus on balancing improved outcomes with economic and resistance considerations.” – by Alaina Tedesco

Disclosure: The researchers report funding by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development.