Association of fluoroquinolones or cephalosporin plus macrolide with Clostridioides difficile infection (CDI) after treatment for community-acquired pneumonia

Infect Control Hosp Epidemiol. 2023 Jan;44(1):47-54. doi: 10.1017/ice.2022.60. Epub 2022 Apr 20.


Objective: Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI.

Methods: We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens.

Results: Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70-1.38).

Conclusion: Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.

Publication types

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

MeSH terms

  • Adult
  • Anti-Bacterial Agents / adverse effects
  • Cephalosporins / adverse effects
  • Clostridium Infections* / drug therapy
  • Clostridium Infections* / epidemiology
  • Community-Acquired Infections* / drug therapy
  • Community-Acquired Infections* / epidemiology
  • Fluoroquinolones / adverse effects
  • Humans
  • Macrolides / adverse effects
  • Pneumonia* / drug therapy
  • Retrospective Studies


  • Cephalosporins
  • Fluoroquinolones
  • Macrolides
  • Anti-Bacterial Agents