Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ؎ 18 years (Charlson comorbidity index, 3.8 ؎ 2.4; Horn's index, 1.7 ؎ 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P ‫؍‬ 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P ‫؍‬ 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P ‫؍‬ 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.I n the United States, Clostridium difficile is the most commonly reported pathogen for health setting-acquired infections, causing approximately 500,000 infections and 29,000 deaths (1, 2) annually. Oral metronidazole is a treatment option for C. difficile infection (CDI) and is recommended in the guidelines for the treatment of mild-to-moderate disease (3). However, observational (4) and randomized controlled (5, 6) studies have demonstrated high clinical failure rates in patients with CDI given metronidazole. Colonic concentrations of metronidazole are relatively low and not predictable, and this drug is not considered by many to be an optimal pharmacologic agent for CDI (7). However, the reason for increased clinical failure rates in patients treated with metronidazole is unknown. Mortality rates due to CDI increase in the elderly (8). We hypothesized that metronidazole response rates would also decrease in the elderly. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. MATERIALS AND METHODSStudy design and study sites. This was a retrospective, multicenter cohort study of patients with CDI admitted to three large tertiary care academic institutions in Houston, TX, from January 2009 to August ...

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