Recurrent C. difficile infections more than doubled between 2001 and 2012

Risk factors for multiply recurrent Clostridium difficile infection included being older, being female, having chronic kidney disease, residing in a nursing home, and having taken antibiotics, proton-pump inhibitors, or corticosteroids, the retrospective study found.


The incidence of multiply recurrent Clostridium difficile infection increased dramatically between 2001 and 2012, according to a recent study.

The retrospective cohort study used data on 38 million commercially insured U.S. patients, of whom 45,341 developed C. difficile. Of those patients, 1,669 had multiply recurrent C. difficile infections. Between 2001 and 2012, the annual incidence of C. difficile increased by 42.7% (from 0.4408 to 0.6289 per 1,000 person-years). In the same period, incidence of multiply recurrent infections increased 188.8% (from 0.0107 to 0.0309 per 1,000 person-years). Results were published online July 4 by Annals of Internal Medicine.

Researchers also looked at risk factors for recurrent infection. Compared to patients with non-recurring C. difficile, those with multiply recurrent infection were older (median age, 56.0 years vs. 49.0 years), more likely to be female (63.8% vs. 58.7%), and to have used antibiotics (72.3% vs. 58.8%), proton-pump inhibitors (24.6% vs. 18.2%), or corticosteroids (18.3% vs. 13.7%) within 90 days of C. difficile diagnosis. Chronic kidney disease and diagnosis in a nursing home were also associated with risk for multiply recurrent C. difficile infections (10.4% vs. 5.6% and 2.1% vs. 0.6%, respectively).

The goals of the study included identifying risk factors for multiply recurrent C. difficile and determining how many patients would be candidates for fecal microbiota transplantation in coming years, the study authors noted. Based on the results, demand for fecal transplants and new antimicrobial therapies can be expected to increase considerably, they said. The increase over time in the incidence of multiply recurrent C. difficile infections, even after adjustment for risk factors, may be due to a change in the biology of C. difficile, such as the emergence of the North American pulsed-field gel electrophoresis type 1 strain, the authors speculated.

The identified risk factors for recurrence could be used to adjust treatment algorithms for high-risk patients, including earlier use of fecal transplant. Limitations of the study included that the definitive causes of the observed increase could not be determined and could include factors such as increased testing for C. difficile, although the study largely predated widespread adoption of nucleic acid amplification testing.

An accompanying editorial said this is the largest study to date of multiply recurrent C. difficile and its epidemiology. The editorialists noted additional limitations, including that the study did not include fee-for-service Medicare patients and did not capture some factors associated with recurrent infection which could partially account for the observed increase, including prior fluoroquinolone use.