Clostridioides difficile infection is associated with a large burden on the healthcare system in the United States, according to a systematic literature review and meta-analysis published in JAMA Network Open.

Researchers assessed the incidence of C difficile infection in a hospital setting and the length of hospital stays attributed to C difficile infection. Data from US-based studies since 2000 were extracted from MEDLINE, Cochrane Library Databases, and the Cumulative Index of Nursing and Allied Health Complete, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses, and Meta-analysis of Observational Studies in Epidemiology protocols. Researchers extracted data on study design, population, setting, controls, outcomes, and biases for each study to decide if the study met the inclusion criteria.

Of the 86 studies included in the review, 66 evaluated the incidence of C difficile infection and 20 evaluated length of hospital stay due to C difficile infection. Of the 66 studies that evaluated the incidence of C difficile infection, 13 used patient-days as the denominator. The incident rate varied from 2.8 to 15.8 cases of C difficile infection per 10,000 patient-days among the studies, and their pooled incidence of hospital-onset C difficile infection was calculated to be 8.3 cases per 10,000 patient-days.

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A total of 14 studies included both inpatients and outpatients, of which 8 reflected data in a denominator of person-years. One of these studies, which evaluated the annual incidence of C difficile infection and multiply recurrent infection per 1000 person-years in the US, found that the incidences increased by 42.7% and 188.8%, respectively, between 2001 and 2012. Another study on C difficile infection rates among people aged >65 years showed a rate of 677 per 100,000 person-years, while another study reported an incidence of C difficile infection at 14.9 per 10,000 person-years within a 1 year period. The meta-analysis authors noted that these studies were too varying in methods, measures and findings to allow for pooling of data into 1 estimate.

Of the 20 studies that evaluated the length of hospital stay due to C difficile infection, 13 used propensity score-matching on adults and found the mean difference in the length of hospital stay between patients with C difficile infection and those without varied from 3 to 10.3 days.

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The study had several limitations, including that the majority of the studies included were of moderate-to-low quality evidence, with potential overestimates in outcomes. Further, the definition of C difficile infection was based on the International Classification of Diseases, 9th Revision and only including studies performed in the United States.

The researchers concluded that “[p]ooled estimates from currently available literature suggest that [C difficile infection] is associated with a large burden on the [US] health care system.”


Marra AR, Perencevich EN, Nelson RE, et al. Incidence and outcomes associated with Clostridium difficile infections: A systematic review and meta-analysis. JAMA Netw Open. 2020;3(1):e1917597.