Vancomycin better first-line choice for severe C. diff

Vancomycin better first-line choice for severe C. diff

But selecting out VRE a concern

Hospitalized patients with severe C. difficile-associated diarrhea were more likely to recover if they received vancomycin rather than the antibiotic metronidazole, which is typically the first-line therapy, an epidemiologist reports.

The randomized, controlled, double-blind trial included 150 people, 81 of whom had mild diarrhea and 69 of whom had severe diarrhea.¹ Among the mild group, the cure rates were comparable for metronidazole (37 of 41, or 90%) and vancomycin (39 of 40, or 98%). But in the group with severe disease, only 29 of 38 (76%) were cured with metronidazole, vs. 30 of 31 (97%) who received vancomycin. Vancomycin might be increasingly important as a first-line drug for severe C. diff infections due to the emergence of the new virulent epidemic ribotype 027 strain.

"Considering the increased severity of C. difficile-associated diarrhea, vancomycin needs to be considered first in the more serious cases," says principal investigator Fred A. Zar, MD, professor of medicine at the University of Illinois in Chicago. "One of the frustrations of C. diff is that 10% to 20% of people who are cured have a relapse and must be treated again, and 10% to 20% of those people will have a third relapse. The problem is either that we can't eradicate the organism completely from the bowel with current therapies and/or patients are getting reinfected."

Currently, metronidazole is the most often prescribed and least expensive treatment option for CDAD. "The CDC and most of the guidelines out there recommend metronidazole as the first-line drug for C. difficile," Zar says. "Some [researchers and clinicians] have said in severe disease you might want to start with vancomycin, but nobody has ever proven it. It's just kind of a gut feeling — no pun intended. I had that feeling, too, when I designed the study but I wanted to see if we could have some scientific evidence."

In addition, Zar's study adds to accumulating evidence that an increasing number of patients may be failing on metronidazole. Typically, however, C. diff patients are treated with alternative therapy only if they present with or advance to more severe disease. While there are fewer reported cases of treatment failure involving vancomycin, there is some concern that treatment of C. diff with oral vancomycin in the hospital could lead to selection of other organisms resistant to vancomycin. There have been many reported cases of selection of vancomycin-resistant enterococci (VRE) species following treatment with vancomycin, and intermediate and full vancomycin resistance has been documented in Staphylococcus aureus.

"Everybody that has looked for high-level resistance to vancomycin [in C. diff] hasn't found it and we have been using vancomycin for decades for this disease," Zar says. "We will eventually see resistance I'm sure, just as we eventually saw highly resistant staph. But I don't think resistance to C. diff is the issue as much as the concern that vancomycin selects out resistant enterococci. What I would like to do in the future is to compare the two drugs again and see which one — if either one — selects out VRE more than the other. That might be a moot point if they both do it to the same degree."

Reference

1. Zar FA, Bakkanagari SR, Moorthi K, et al. Vancomycin is superior to metronidazole in the treatment of severe Clostridium difficile-associated diarrhea (CDAD). Abstract 686. Infectious Disease Society of America. Toronto; Oct. 12-15, 2006.