Multiply Recurrent C difficile Infection Rate 4 Times Higher Than CDI

The rate of multiply recurrent Clostridium difficile (mrCDI) was found to be more than 4 times higher than that of original CDI, with important implications for treatment decisions.

Recurrences of Clostridium difficile infection (CDI) have been increasing at significantly faster rates than rates for initial CDI, according to a recent retrospective cohort study reported in the Annals of Internal Medicine.1 From 2001 to 2012, multiply recurrent CDI (mrCDI) increased by 188.8%, more than 4 times the CDI rate, which only increased by 42.7% during the same period. The huge increase in mrCDI was independent of any known risk factors for CDI.

The estimated recurrence rate of CDI is 13% to 50% following initial treatment.2 Standard treatment for mrCDI is fecal microbiota transplantation (FMT), a therapy that is extremely costly and in which the long-term safety and efficacy profile are not well established. In anticipation of a corresponding marked increase in the demand for mrCDI therapies, the investigators in the current study sought to identify potentially modifiable risk factors.

Using records from the Optum Clinformatics Database, the researchers established a cohort of 38,911,718 patients with a median age of 31 (range 16 to 45) from a broad number of US health plans who were followed for a median of 1.9 years (range 0.8 to 3.8) after CDI. A total of 45,341 patients had at least 1 CDI episode during the study period. Compared with patients who did not develop CDI, patients who did were older (median 49 and 56, respectively), and more patients were women (63.8% vs 58.7%, respectively).

The investigators reported an annual increase of 8% in the relative odds of an individual developing mrCDI. Features that pointed to the likelihood of mrCDI included the use of antibiotics during the previous 90 days for any conditions other than CDI, or the use of corticosteroids. Chronic kidney disease was the only comorbid condition that indicated higher mrCDI risk (10.4% vs 5.6%; adjusted odds ratio (aOR) 1.49; CI 1.24 to 1.80), while inflammatory bowel disease and diabetes mellitus did not. Patients residing in a nursing home at the time of the CDI were also at higher risk of mrCDI (aOR, 1.99; CI 1.34 to 2.93]. In addition, there was a regional influence suggesting higher risks in people living in the Northeast and Midwestern United States.

The investigators suggested that consideration of these risk factors could help inform treatment decisions, such as altering the type of initial therapy from FMT to a potentially safer therapy, or using FMT earlier in the course of the disease for greater efficacy.

Several limitations to this study were noted, most prominently the retroactive evaluation of claims data rather than recruiting live patients. Information in the claims files on the specific strain of C diffiicile responsible for each infection was lacking. This study design also blocked the investigators from being able to identify the cause of the significant upswing in mrCDI.

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  1. Ma GK, Brensinger CM, Wu Q, Lewis JD. Increasing incidence of multiply recurrent Clostridium difficile infection in the United States: a cohort study [published online July 4, 2017]. Ann Intern Med. doi:10.7326/M16-2733
  2. Garey KW, Sethi S, Yadav Y, DuPont HL. Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect. 2008;70:298-304. doi:10.1016/j.jhin.2008.08.012