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

Abstract

There are several antibiotic regimens to treat community-acquired pneumonia (CAP). 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? 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 48h of admission. Patients with severe CAP requiring ICU admission in the first 48h 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. 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. 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.