title: The magnitude and duration of Clostridium difficile infection risk associated with antibiotic therapy: a hospital cohort study.
abstract: Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.
authors.affiliation: Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Brown
authors.affiliation: Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Fisman
authors.affiliation: Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rahim
authors.initials: R
authors.lastname: Moineddin
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nick
authors.initials: N
authors.lastname: Daneman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000453:epidemiology*; D015331:Cohort Studies; D003428:Cross Infection / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents