Review of Existing Studies Supports Recommended Use of Vancomycin in Adults With C Diff

When the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) updated their guideline for the management of Clostridium difficile (C diff) infection (CDI) in adults last year, not everyone was on board.

At issue was the recommendation for the use of either vancomycin (125 mg orally 4 times per day) or fidaxomicin (200 mg twice daily for 10 days) over metronidazole for an initial episode of C diff. As noted by the authors of a study published in the June 2018 issue of Cureus, “Multiple studies have shown fidaxomicin to have a substantially higher in vitro activity against C difficile compared to vancomycin with a more prolonged post-antibiotic effect.”

Of course, fidaxomicin is more expensive than vancomycin; however, the investigators on the aforementioned study suggest that it may, in fact, be the more “cost-effective option.”

Now, a new review of outcomes data published in Annals of Pharmacotherapy indicates vancomycin “is more effective than metronidazole”…with a “more favorable pharmacokinetic, safety, and tolerability profile.”

“The IDSA/SHEA guidelines…note the preferred use of oral vancomycin or fidaxomicin… for the first episode of non-severe CDI; however, clinical efficacy data comparing metronidazole and vancomycin for patients with non-severe CDI, especially data available at the time of the guideline revision process, are limited,” study co-author Katherine V. Sarna, PharmD, clinical assistant professor/clinical pharmacist at the University of Illinois-Chicago, told Contagion®.

“We decided to explore this topic because of the buzz that’s generated whenever we have to make treatment decisions for patients experiencing a first-episode of non-severe CDI. On one hand, you have new national guidelines recommending vancomycin or fidaxomicin over metronidazole for these patients with non-severe disease. On the other hand, the evidence backing these recommendations are limited in this patient subgroup. Further complicating clinical-decision making, the clinical criteria used to distinguish patients with non-severe versus severe CDI has still not been validated and continues to vary across clinical studies.”

In their review of existing literature, Dr. Sarna and her colleagues identified 9 clinical studies (interventional and observational), 5 meta-analyses, and 1 cost-effectiveness analysis comparing oral metronidazole and vancomycin for the treatment of mild-to-moderate CDI via a Medline literature search (including studies published since the guideline update in February 2018 through November 2018), using the search terms “metronidazole,” “vancomycin,” and “Clostridium/Clostridioides difficile.” They included all English-language papers, and added other references from a review of literature citations in their final analysis.

The investigators found that in several of these studies “improved treatment response with vancomycin as compared with metronidazole…reached statistical significance,” and that, based on these published studies, “cost per case treated appears to be lower with vancomycin compared with metronidazole” in hospitalized patients.

“Clinical efficacy data have not unequivocally demonstrated vancomycin’s superiority to metronidazole in patients with non-severe CDI given the available studies are underpowered for this subgroup; however, there is a confluence in the data that suggest vancomycin is more effective in this population, and in fact, a recent network meta-analysis identified improved outcomes with vancomycin in this subgroup relative to metronidazole,” noted Dr. Sarna. “And, if you take a step back from the limited efficacy data, one must also consider oral vancomycin’s superior safety profile based on trial data combined with its ability to reach high concentrations at the sight of action, which make it a more optimal agent for treating non-severe CDI. We hope this information will help clinicians make more informed decisions about the use of metronidazole and vancomycin for the treatment of non-severe CDI, while weighing efficacy, toxicity, and pharmacokinetic/pharmacodynamic data.”