Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection

Antimicrob Agents Chemother. 2020 Mar 24;64(4):e02169-19. doi: 10.1128/AAC.02169-19. Print 2020 Mar 24.

Abstract

Clostridioides difficile infection (CDI) is a health care-associated infection associated with significant morbidity and cost, with highly varied risk across populations. More effective, risk-based prevention strategies are needed. Here, we investigate risk factors for hospital-associated CDI in a large integrated health system. In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (i) hospital-onset and (ii) health care-facility-associated, community-onset CDI. We then evaluated the risk associated with antibiotic exposure, including that of specific agents, using multivariable logistic regression. A total of 2,356 cases of CDI among 506,068 admissions were identified (incidence, 46.6 per 10,000). Prior antibiotic use was the dominant risk factor, where for every antibiotic day of therapy prior to the index admission, the odds of subsequent CDI increased by 12.8% (95% confidence interval [CI], 12.2 to 13.4%; P < 0.0001). This was a much stronger association than was inpatient antibiotic exposure (odds ratio [OR], 1.007 [95% CI, 1.005 to 1.009]; P < 0.0001). The highest-risk antibiotics included second-generation and later cephalosporins (especially oral), carbapenems, fluoroquinolones, and clindamycin, while doxycycline and daptomycin were associated with a lower CDI risk. We concluded that cumulative antibiotic exposure prior to admission is the greatest contributor to the risk of subsequent CDI. Most classes of antibiotics carry some risk, which varies by drug and route. This information may be useful for antimicrobial stewardship efforts.

Keywords: Clostridioides difficile infection; antibiotic stewardship; antibiotics; health care associated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological / drug effects*
  • Adaptation, Physiological / genetics
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Antimicrobial Stewardship*
  • Carbapenems / adverse effects
  • Carbapenems / therapeutic use
  • Cephalosporins / adverse effects
  • Cephalosporins / therapeutic use
  • Clindamycin / adverse effects
  • Clindamycin / therapeutic use
  • Clostridioides difficile / drug effects*
  • Clostridioides difficile / genetics
  • Clostridium Infections / drug therapy*
  • Cross Infection / chemically induced
  • Cross Infection / drug therapy
  • Cross Infection / microbiology*
  • Daptomycin / adverse effects
  • Daptomycin / therapeutic use
  • Doxycycline / adverse effects
  • Doxycycline / therapeutic use
  • Drug Resistance, Bacterial / genetics
  • Female
  • Fluoroquinolones / adverse effects
  • Fluoroquinolones / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Cephalosporins
  • Fluoroquinolones
  • Clindamycin
  • Doxycycline
  • Daptomycin