Large variations in Clostridioides difficile infection risk resulting from antibiotic courses used for the same indications have been identified, according to results of a study published in Clinical Infectious Diseases. It was also shown that risk could be substantially reduced if prescribers chose shorter durations of lower-risk agents.

Using a longitudinal case-cohort analysis that represented >90% of nursing home residents in Ontario, Canada, between 2012 and 2017, investigators estimated risks for C difficile infection associated with receipt of specific antibiotic courses.

A total of 1708 cases of C difficile were identified, which equated to 1.27 per 100,000 resident-days; roughly 20% of the study cohort received antibiotic treatment in the 90 days before the study period. The 90-day risk of developing C difficile infection was 0.81 and 1.90 per 1000 among patients who did not receive antibiotics and those who did, respectively. There was a 1.80-fold increase in the adjusted relative risk (ARR) for C difficile infection linked to a 7-day course of antibiotics.

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Longer antibiotic durations were associated with increased risk. Courses of 10 and 14 days incurred 12% (adjusted relative risk, 1.12; 95% CI, 1.09-1.14) and 27% (ARR, 1.27; 95% CI, 1.21-1.30) more risk, respectively, compared with 7-day courses. Conversely, a 5-day course was associated with a 9% decrease in risk for C difficile infection (ARR, 0.91; 95% CI, 0.90-0.93). The study authors highlighted that previous studies have demonstrated that antibiotic courses of 5 to 7 days have similar clinical efficacy compared with a longer course of infections such as uncomplicated urinary tract infections, pneumonia, and cellulitis.

For 7-day courses with similar indications, moxifloxacin resulted in 121% more risk than amoxicillin (ARR, 2.21; 95% CI, 1.67-3.08), ciprofloxacin demonstrated an 89% increased risk vs nitrofurantoin (ARR, 1.89; 95% CI, 1.45-2.68), and clindamycin resulted in 112% more risk than cloxacillin (ARR, 2.12; 95% CI, 1.32-3.78).

The study results were limited, in that they did not capture antibiotics administered during hospitalization, and therefore patients with recent hospitalization in the 30 days before the main analysis were excluded. The effect of antibiotic combinations could not be addressed because investigators only examined residents receiving a single antibiotic type in the prior 90 days. This was done to address confounding as a result of multiple antibiotic exposures. The study also only delineated comparative risks of C difficile, and did not evaluate other differences in antibiotic harms and benefits. It may also lack generalizability to younger patients and community-dwelling seniors.

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The investigators believe this work still provides much needed data on antibiotic risks, which previously could not be easily quantified. Furthermore, the results “can be used by clinicians to weigh the potential harms of antibiotic prescribing choices to prevent C. difficile infection and improve patient outcomes,” the researchers wrote.


Brown KA, Langford B, Schwartz KL, Diong C, Garber G, Daneman N. Antibiotic prescribing choices and their comparative C. difficile infection risks: a longitudinal case-cohort study [published online February 18, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa124

This article originally appeared on Gastroenterology Advisor