Thirty-day all-cause mortality among patients with severe Clostridium difficile infection (CDI) was significantly lower when vancomycin was used as first-line therapy compared with metronidazole, according to a retrospective studying that included more than 10,000 patients.
There was no difference in CDI recurrence rates between treatment groups.
"This is the largest study to date to compare vancomycin and metronidazole in a real-world setting and 1 of the few studies focused on downstream outcomes of CDI," write Vanessa W. Stevens, PhD, from the Veterans Affairs Salt Lake City Health Care System in Utah, and colleagues.
"[I]mproved clinical cure and mortality rates may warrant reconsideration of current prescribing practices," they continue, writing in an article published online February 6 in JAMA Internal Medicine.
Current guidelines recommend metronidazole as initial treatment, especially for mild to moderate cases of CDI.
For severe cases, guidelines published in 2010 by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America do recommend oral vancomycin, according to Erik R. Dubberke, MD, MSPH, associate professor of medicine and director, Section of Transplant Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri.
However, despite evidence that the use of vancomycin is increasing, "it has taken several years for people to adopt these recommendations," Dr Dubberke told Medscape Medical News.
The new data confirm findings from smaller studies and more recently published randomized controlled trials showing no difference in recurrence between the two treatments, but patients who receive oral vancomycin "are more likely to respond to treatment," he said.
However, this study was unique, in that "it was large enough to demonstrate a survival advantage, not just a better response to treatment," added Dr Dubberke, who was not involved in the research.
Severe Infections Best Treated With Vancomycin
In a retrospective, propensity-matched, intention-to-treat cohort study, Dr Stevens and colleagues analyzed data from patients treated for CDI in the Veterans Affairs Healthcare System between January 1, 2005, and December 31, 2012. The outcomes of primary interest were all-cause 30-day mortality and recurrent CDI.
The diagnosis of CDI was confirmed through analysis of stool samples for the C difficile toxin or toxin gene. Propensity matching was used to control for possible confounding differences between patients receiving vancomycin or metronidazole.
During the study period, a total of 47,471 patients met the inclusion criteria. Of these individuals, 2068 (4.4%) received vancomycin as first-line therapy and were matched with 8069 patients treated with metronidazole. Among those 10,137 patients were 3130 individuals with severe CDI: 629 (20.1%) who received vancomycin and 2501 (79.9%) who were treated with metronidazole.
All-cause 30-day mortality for the group as a whole was 10.2%. However, this broke down into 6.7% for patients with mild to moderate CDI and 18.9% for severe CDI.
"Overall," the authors observe, "patients who received vancomycin had a lower risk of mortality compared with patients treated with metronidazole (8.6% vs 10.6%; P = .01)" — a 20% reduction in mortality.
This was largely a result of the difference in mortality among patients with severe CDI. For severe CDI, treatment with vancomycin was associated with a mortality rate of 15.3% compared with 19.8% among patients treated with metronidazole (P = .01). In contrast, 30-day mortality among patients with mild to moderate CDI was 5.9% with vancomycin and 6.9% among patients treated with metronidazole (P = .22).
The incidence of CDI has increased during the last 20 years for reasons that mostly remain unclear, Dr Dubberke said. Recurrence rates range from 15% to 50%, largely because of alterations in the gut microbiome, which can be exacerbated by antibiotic therapy, "placing a patient at high risk for CDI to recur once treatment is stopped."
In this study, approximately 16% of patients developed recurrent infection. The recurrence rates were similar across all treatment and severity groups, the authors write.
The patients were not randomly assigned into treatment groups, so there may have been potential differences that affected the study outcome. Also, despite the use of propensity matching, there may have been other, unmeasured confounding factors, the authors write. The study also did not account for changes in CDI treatment over time and may have included patients who were colonized with C difficile, but did not have clinical symptoms.
Nevertheless, they conclude, the results "build on existing evidence that vancomycin may be preferable to metronidazole, particularly for patients with severe" CDI.
The authors have disclosed no relevant financial relationships. Dr Dubberke reports having received research support from Sanofi-Pasteur, Pfizer, Merck, and Rebiotix, and consulting for those companies, as well as for Valneva, GSK, and Nestle.
JAMA Intern Med. Published online February 6, 2017. Full text