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Concomitant antibiotic use during treatment for Clostridium difficile infection (CDI) increases the risk of recurrence. Across a network of children’s hospitals, 46% of patients treated for CDI received concomitant antibiotics for a median of 7 days. Concomitant antibiotic use was more common among patients with malignancies, and solid organ or bone marrow transplant. Unnecessary concomitant antibiotic use in CDI patients is a potential target for pediatric antimicrobial stewardship.

Importance Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. Objective 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. Design, Setting, and Participants This retrospective, propensity-matched cohort study evaluated patients treated for CDI, defined as a positive laboratory test result for the presence of C difficile toxins or toxin genes in a stool sample, in the US Department of Veterans Affairs health care system from January 1, 2005, through December 31, 2012. Data analysis was performed from February 7, 2015, through November 22, 2016. Exposures Treatment with vancomycin or metronidazole. Main Outcomes and Measures The outcomes of interest in this study were CDI recurrence and all-cause 30-day mortality. Recurrence was defined as a second positive laboratory test result within 8 weeks of the initial CDI diagnosis. All-cause 30-day mortality was defined as death from any cause within 30 days of the initial CDI diagnosis. Results A total of 47 471 patients (mean [SD] age, 68.8 [13.3] years; 1947 women [4.1%] and 45 524 men [95.9%]) developed CDI, were treated with vancomycin or metronidazole, and met criteria for entry into the study. Of 47 147 eligible first treatment episodes, 2068 (4.4%) were with vancomycin. Those 2068 patients were matched to 8069 patients in the metronidazole group for a total of 10 137 included patients. Subcohorts were constructed that comprised 5452 patients with mild to moderate disease and 3130 patients with severe disease. There were no differences in the risk of recurrence between patients treated with vancomycin vs those treated with metronidazole in any of the disease severity cohorts. Among patients in the any severity cohort, those who were treated with vancomycin were less likely to die (adjusted relative risk, 0.86; 95% CI, 0.74 to 0.98; adjusted risk difference, –0.02; 95% CI, –0.03 to –0.01). No significant difference was found in the risk of mortality between treatment groups among patients with mild to moderate CDI, but vancomycin significantly reduced the risk of all-cause 30-day mortality among patients with severe CDI (adjusted relative risk, 0.79; 95% CI, 0.65 to 0.97; adjusted risk difference, –0.04; 95% CI, –0.07 to –0.01). Conclusions and Relevance Recurrence rates were similar among patients treated with vancomycin and metronidazole. However, the risk of 30-day mortality was significantly reduced among patients who received vancomycin. Our findings may further justify the use of vancomycin as initial therapy for severe CDI.

OBJECTIVE:The purpose of this study was to identify the risk factors during the incident Clostridium difficile infection (CDI) episode, associated with developing recurrent CDI within 60 days, among hospitalized children that may be amenable to intervention.METHODS:This was a retrospective cohort study of pediatric patients hospitalized at a freestanding children’s hospital from January 1, 2003, to December 31, 2010. Patients were eligible if they were RESULTS:During the study period, there were 612 unique patients with an incident CDI episode; 65 (10.6%) experienced at least 1 recurrence. Patients with any complex chronic condition were 4.0 (95% confidence interval [CI]: 1.2–13.9) times more likely to experience recurrence. Patients with a malignancy and those who received non-CDI antibiotics at any time during CDI treatment were 2.3 (95% CI: 1.3–4.0) and 2.8 (95% CI: 1.2–6.9) times more likely to experience recurrence, respectively.CONCLUSIONS:The presence of underlying comorbidities, malignancies, and treatment with non-CDI antibiotics during CDI treatment were the most important risk factors for recurrence. Efforts to reduce unnecessary courses of non-CDI antibiotics could lower the risk of CDI recurrence.