Outcomes associated with empiric azithromycin use among patients hospitalized with non-severe community-acquired pneumonia: emulation of a target trial
Recommended Citation
Gupta AB, Walzl E, Ratz D, Horowitz JK, McLaughlin E, Pearlman T, Czilok T, Gandhi T, Petty LA, Malani AN, Paje D, Misra P, Kaatz S, Bernstein S, Younas M, Flanders SA, Vaughn VM. Outcomes associated with empiric azithromycin use among patients hospitalized with non-severe community-acquired pneumonia: emulation of a target trial. Clin Infect Dis. 2026.
Document Type
Article
Publication Date
4-3-2026
Publication Title
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Abstract
BACKGROUND: There remains equipoise regarding the benefit of empiric azithromycin with beta-lactam therapy in patients hospitalized with non-severe CAP.
METHODS: We performed a target trial emulation using a propensity-weighted cohort from 68 hospitals in Michigan. Adult patients hospitalized with non-severe CAP receiving beta-lactam antimicrobial therapy with or without azithromycin were included. CAP was defined by ICD-10 discharge diagnosis code of pneumonia and >2 signs/symptoms of pneumonia with radiographic findings. Patients with severe CAP, risk factors for multi-drug-resistant organisms, a macrolide allergy, or who received non-standard CAP treatment, doxycycline, an alternative macrolide, or a fluroquinolone were excluded. Time zero was encounter start. The primary outcome was time (days) to clinical stability. Secondary outcomes included composite 30-day mortality and rehospitalization, 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% (17,822/19,010) received empiric azithromycin. After IPTW, there was no difference in time to clinical stability between those receiving and not receiving empiric azithromycin (3 [IQR 3-4] vs 3 days [IQR 3-4], 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=0.0004). 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).
CONCLUSION: Adding azithromycin to beta-lactam therapy in patients hospitalized with non-severe CAP was not associated with time to clinical stability but was associated with lower composite 30-day mortality and rehospitalization.
PubMed ID
41931457
ePublication
ePub ahead of print
