Metronidazole Comparable to Vancomycin for Mild C Diff Infections

A study by investigators from the Providence Veterans Affairs Medical Center indicates that metronidazole is an appropriate treatment option for mild cases of Clostridium difficile infection, despite new guidelines which no longer recommend the antibiotic for initial and non-severe C diff cases.

In the new study published in the journal Clinical Infectious Diseases, investigators aimed to compare the effectiveness of metronidazole with vancomycin in patients with mild C diff infection. The study comes following the 2018 release of updated clinical practice guidelines from the Infectious Diseases Society of America. Prior to the new guidelines, metronidazole was recommended over vancomycin as a first-line antibiotic for mild to moderate cases of C diff. The new guidelines recommend either vancomycin or fidaxomicin over metronidazole for an initial C diff infection episode based on evidence showing better outcomes associated with vancomycin as compared to metronidazole in patients with severe C diff infection. The authors note that, to their knowledge, this is the first study to focus specifically on identifying predictors of success and the first to compare treatment options in patients with an initial episode of mild C diff infection.

For the study, investigators conducted a 2-stage analysis among a large national cohort of veterans with a mild and first episode of C diff infection, defined as a stool sample positive for C diffi toxin and 2 or more days of C diff infection treatment. They defined successful treatment as patients who did not die or have a C diff infection recurrence at day 30, and treatment failure as those who died or had a C diff infection recurrence within 30 days following treatment. Among 3656 patients with mild C diff infection and treated with metronidazole, the study team identified 3282 patients with success at day 30 post-treatment and 374 patients without success.

Based on multivariable analysis, the investigators identified younger age as the only independent predictor of success, finding that those younger than 65 had odds of success 1.63 times higher (95% confidence interval [CI] 1.29 — 2.06) than those aged 65 years or older. “We found that for patients 65 years old or younger, metronidazole and vancomycin had similar success in the treatment of initial mild C diff infection,” study co-author Haley J. Appaneal, PharmD, said in an interview with Contagion®, noting that older patients are more likely than younger patients to have age-related declines in the immune system and other chronic diseases such as diabetes or obesity affecting treatment outcomes. Older patients are also more frequently exposed to antibiotics and health care settings than younger patients. “All of these factors may have played a role in why patients 65 years old or younger were more likely to have successful outcomes than older patients.”

Predictors of treatment failure identified in the study included principle diagnosis of C diff infection, current intestinal infection, current respiratory failure, malignancy, previous hospital or long-term care exposure, hypoalbuminemia, high body mass index, and previous probiotic exposure, and may indicate that metronidazole should be avoided for certain patient subgroups, investigators noted. The study did not include patients with severe cases of C diff infection and thus doesn’t provide guidance for severe infection, said Appaneal. “We hope that for those treating cases of initial mild C diff infection that metronidazole is still considered as an option for patients who are younger and generally healthy.”