Comparative Effectiveness of First-Line and Alternative Antibiotic Regimens in Hospitalized Patients With Nonsevere Community-Acquired Pneumonia: A Multicenter Retrospective Cohort Study

Chest. 2024 Jan;165(1):68-78. doi: 10.1016/j.chest.2023.08.008. Epub 2023 Aug 11.


Background: There are several antibiotic regimens to treat community-acquired pneumonia (CAP).

Research question: In patients hospitalized to a non-ICU ward setting with CAP, is there a difference between first-line and alternative antibiotic regimens (β-lactam plus macrolide [BL+M], β-lactam [BL] alone, respiratory fluoroquinolone [FQ], or β-lactam plus doxycycline [BL+D]) in terms of in-hospital mortality?

Study design and methods: This retrospective cohort study included consecutive patients admitted with CAP at 19 Canadian hospitals from 2015 to 2021. Taking a target trial approach, patients were categorized into the four antibiotic groups based on the initial antibiotic treatment within 48 h of admission. Patients with severe CAP requiring ICU admission in the first 48 h were excluded. The primary outcome was all-cause in-hospital mortality. Secondary outcome included time to being discharged alive. Propensity score and overlap weighting were used to balance covariates.

Results: Of 23,512 patients, 9,340 patients (39.7%) received BL+M, 9,146 (38.9%) received BL, 4,510 (19.2%) received FQ, and 516 (2.2%) received BL+D. The number of in-hospital deaths was 703 (7.5%) for the BL+M group, 888 (9.7%) for the BL group, 302 (6.7%) for the FQ group, and 31 (6.0%) for the BL+D group. The adjusted risk difference for in-hospital mortality when compared with BL+M was 1.5% (95% CI, -0.3% to 3.3%) for BL, -0.9% (95% CI, -2.9% to 1.1%) for FQ, and -1.9% (95% CI, -4.8% to 0.9%) for BL+D. Compared with BL+M, the subdistribution hazard ratio for being discharged alive was 0.90 (95% CI, 0.84-0.96) for BL, 1.07 (95% CI, 0.99-1.16) for FQ, and 1.04 (95% CI, 0.93-1.17) for BL+D.

Interpretation: BL+M, FQ, and BL+D had similar outcomes and can be considered effective regimens for nonsevere CAP. Compared with BL+M, BL was associated with longer time to discharge and the CI for mortality cannot exclude a small but clinically important increase in risk.

Keywords: antibiotic treatment; community-acquired pneumonia; mortality.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Canada / epidemiology
  • Community-Acquired Infections* / drug therapy
  • Drug Therapy, Combination
  • Humans
  • Length of Stay
  • Macrolides / therapeutic use
  • Pneumonia* / drug therapy
  • Retrospective Studies
  • beta-Lactams / therapeutic use


  • Anti-Bacterial Agents
  • beta-Lactams
  • Macrolides