Increasing Incidence of Multiply Recurrent Clostridium difficile Infection in the United States: A Cohort Study

Ann Intern Med. 2017 Aug 1;167(3):152-158. doi: 10.7326/M16-2733. Epub 2017 Jul 4.


Background: Clostridium difficile infection (CDI), the most common health care-associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI).

Objective: To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI.

Design: Retrospective cohort study.

Setting: United States.

Participants: 38 911 718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45 341 developed CDI.

Measurements: Age- and sex-standardized incidence rates for CDI and mrCDI.

Results: From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI.

Limitation: The primary analyses included only commercially insured patients in the United States.

Conclusion: Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies.

Primary funding source: National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases.

MeSH terms

  • Adolescent
  • Adult
  • Clostridioides difficile*
  • Clostridium Infections / epidemiology*
  • Clostridium Infections / therapy
  • Fecal Microbiota Transplantation
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • United States / epidemiology
  • Young Adult