Study: Vancomycin should be go-to drug for severe C diff

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A study today in JAMA Internal Medicine indicates that vancomycin can reduce risk of all-cause mortality for patients with severe Clostridium difficile infection.

The authors of the study say the findings reinforce the view that vancomycin should be the primary antibiotic for the treatment of severe C difficile, despite concerns over cost and vancomycin resistance in other types of healthcare-associated infections. While clinical guidelines recommend vancomycin for initial episodes of severe C difficile, metronidazole—the drug of choice to mild-to-moderate infection—is often used as an alternative.

Comparative effectiveness

For years, vancomycin and metronidazole were considered roughly equal in their ability to cure initial C difficile episodes and prevent recurrence of the disease, which occurs in approximately 35% of patients. But more recent studies have indicated that patients treated with metronidazole are less likely to be cured than those who receive vancomycin, particularly those with severe infections.

That's why clinical guidelines from groups like Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend vancomycin for patients with severe infections.

In addition, evidence is starting to emerge that vancomycin may be the superior treatment altogether.

"Even though we've always thought that they were sort of equivalent, and then later they were equivalent just for severe cases, now we're starting to see more and more that vancomycin is probably better all the way around," lead author Vanessa Stevens, PhD, an assistant professor in the University of Utah College of Pharmacy, told CIDRAP News.

To get a more complete picture of the comparative effectiveness of the two treatments, Stevens said, she and her colleagues wanted to look at the secondary consequences of antibiotic choice, particularly recurrence and mortality. According to the study, patients often live in fear of recurrent infection, and previous reviews have shown that roughly 25% of patients with C difficile—which disproportionately affects people who have underlying conditions and are immunocompromised—die within 30 days of diagnosis. Yet these consequences are often overlooked in clinical trials.

Using data from the Veterans Administration (VA) Healthcare System, Stevens and her colleagues conducted a retrospective, propensity-matched cohort study of more than 10,000 patients treated for C difficile with oral vancomycin or metronidazole from 2005 through 2012. Of the 10,137 patients included in the study with any severity of the disease, 5,452 were deemed to have mild-to-moderate C difficile infection, and 3,130 were diagnosed as having severe C difficile.

Analysis of the data showed that there was no difference in risk of recurrence between those treated with vancomycin or metronidazole in any of the severity groups. And in patients with mild-to-moderate disease, there was no significant difference found in the risk of all-cause 30-day mortality. But among the patients with severe infection, patients treated with vancomycin were 4% less likely to die within 30 days of any cause than those treated with metronidazole. Stevens and her colleagues calculated that to prevent one death among patients with severe C difficile infection, 25 would need to be treated with vancomycin.

"This basically means that if you have severe C difficile, you definitely should be treated with vancomycin and not with metronidazole," Stevens said. The mortality benefit was much more pronounced among severely infected patients, she explained, because they are the most likely to die from their infection.

Stevens said the findings, taken together with other recent studies that indicate vancomycin is the better option for severe infection, suggest that physicians need to start looking more closely at how they approach C difficile treatment. "Just reflexing to metronidazole really isn't the optimal approach anymore," she said.

Cost and resistance

Yet despite the recommendations of groups like the IDSA and SHEA, the study shows that metronidazole continues to be the primary treatment option, even for patients with severe C difficile. Though the number of severely infected patients treated with vancomycin did rise over the course of the study, nearly half of those patients did not receive vancomycin in 2012.

One of the main reasons metronidazole has become the primary option is cost. Metronidazole is significantly less expensive than oral vancomycin tablets. A 2008 article in Clinical Infectious Diseases estimated the cost-per-day of vancomycin at $70, compared with $2 a day for metronidazole. Another reason is the concern that the use of vancomycin could promote the emergence of vancomycin-resistant Enterococci (VRE), a growing problem in healthcare settings.

Stevens said these are both important concerns, and that clinicians need to weigh the risks and benefits of both treatments, though she believes that the risk of patients dying from C difficile at the moment is a bigger problem than VRE. For now, she said, the most sensible approach may be to focus on vancomycin therapy for the most severe C difficile patients.

"The picture is still incomplete, but I think we can potentially improve outcomes for patients with C difficile, just by making sure that patients who have severe disease are given vancomycin," Stevens said.

Going forward, she added, more research is needed on cost effectiveness and vancomycin resistance.

The Centers for Disease Control and Prevention (CDC) estimates that C difficile causes 250,000 infections, 14,000 deaths, and at least $1 billion in excess medical costs per year.

See also:

Feb 6 JAMA Intern Med study

 

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