Similar clinical outcomes in mild/moderate Clostridium difficile infection with metronidazole versus vancomycin

1. In this retrospective cohort study, clinical outcomes and recurrence rates of mild to moderate Clostridium difficile infection (CDI) were similar among patients initially treated with metronidazole versus vancomycin.

2. Among patients with severe CDI, 30-day mortality risk was significantly decreased among those initially treated with vancomycin, further adding to the body of evidence that suggests using vancomycin as first line therapy in severe CDI.

Evidence Rating Level: 2 (Good)

Study Rundown: Clostridium difficile infection (CDI) is a major nosocomial infection with significant morbidity and mortality. Appropriate treatment is crucial to decrease risk of recurrence and death. Metronidazole is usually the drug of choice for mild to moderate disease, whereas oral vancomycin is used in severe disease. However, longer term clinical outcomes, such as risk of recurrence, is often not studied. This retrospective, propensity-matched cohort study aimed to evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI.

While no significant difference was found between treatment options in decreasing risk of CDI recurrence, oral vancomycin was associated with an overall lower risk of mortality compared to metronidazole. This difference was largely driven by a decrease in risk of all-cause 30-day mortality in severe CDI. The number needed to treat with vancomycin to prevent 1 death among patients with severe CDI was 25. Strengths of this study included the large cohort size and using propensity-matching. Limitations included this study’s observational nature and use of positive laboratory testing for C. difficile toxin, which may have included colonization instead of true infection.

Click to read the study, published in JAMA Internal Medicine

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In-Depth [retrospective cohort study]: This retrospective, propensity-matched cohort study included data from the VA Healthcare System from January 2005 to December 2012. The study included inpatient and outpatient patients treated for CDI based on laboratory testing indicating presence of the C. difficile toxin or toxin gene in a stool sample. The primary exposure of interest was treatment of CDI with oral vancomycin or metronidazole. The primary outcome of interest was CDI recurrence (second positive laboratory test within 8 weeks of initial CDI diagnosis) and all-cause 30-day mortality (death from any cause within 30 days of initial CDI diagnosis). Clinical information about the CDI episode (severity, other agents used) was gathered. Statistical analysis included propensity-score matching of likelihood of receiving vancomycin, 4:1 ratio of patients receiving metronidazole compared with vancomycin. Multivariable regression was used to calculate outcomes for risk of recurrence and 30-day mortality.

The original cohort included 47,471 patients with CDI, 95.9% of which was men. Of the total patients, 2,068 were treated with vancomycin and they were matched to 8,069 patients treated with metronidazole. The patients were then subdivided by disease severity (5,452 patients with mild to moderate disease and 3,130 patients with severe disease). There was no significant difference for risk of recurrence in both mild to moderate and severe CDI groups when treated by either vancomycin or metronidazole. However, among patients with any disease severity, those treated initially with vancomycin had a decreased risk of death (aRR 0.86; 95% CI 0.74-0.98). Vancomycin use was also found to significantly decrease the risk of all-cause 30-day mortality among patients with severe CDI (aRR 0.79; 95% CI 0.65-0.97).

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