Outcomes Associated With Empiric Azithromycin Use Among Patients Hospitalized With Nonsevere Community-Acquired Pneumonia: Emulation of a Target Trial.

BACKGROUND

There remains equipoise regarding the benefit of empiric azithromycin with beta-lactam therapy in patients hospitalized with nonsevere community-acquired pneumonia (CAP).

METHODS

We performed a target trial emulation using a propensity-weighted cohort from 68 hospitals in Michigan. Adult patients hospitalized with nonsevere CAP receiving beta-lactam antimicrobial therapy with or without azithromycin were included. CAP was defined based on the International Classification of Diseases, Tenth Revision, discharge diagnosis code of pneumonia and ≥2 signs/symptoms of pneumonia with radiographic findings. The primary outcome was time (days) to clinical stability. Secondary outcomes included composite 30-day mortality and rehospitalization, intensive care unit (ICU) transfer, and antibiotic duration.

RESULTS

Of 66 657 patients hospitalized for CAP between September 2015 and July 2024, 28.5% (19 010) met inclusion criteria, of whom 93.8% (17 822 of 19 010) received empiric azithromycin. After inverse probability of treatment weighting, there was no difference in time to clinical stability for those reciving azithromycin (vs not) (3 [interquartile range, IQR 3-4] vs 3 days [IQR 3-4]; adjusted hazard ratio [aHR], 1.00 [0.96-1.05]; P = .91). Empiric azithromycin was associated with lower composite 30-day mortality and rehospitalization (10.8% vs 15.1%; aHR, 0.73 [0.62-0.87]; P = .0004). There were no differences in ICU transfer (0.9% vs 1.4%; aHR, 0.85 [0.48-1.49]; P = .57) or total antibiotic duration (6 [IQR 5-8] vs 7 [IQR 5-9] days, P = .23).

CONCLUSIONS

Adding azithromycin to beta-lactam therapy in patients hospitalized with nonsevere CAP was not associated with time to clinical stability but was associated with lower composite 30-day mortality and rehospitalization.