Effectiveness of Ampicillin-Sulbactam Versus Ceftriaxone for the Initial Treatment of Community-Acquired Pneumonia in Older Adults: A Target Trial Emulation Study.

BACKGROUND

Current guidelines for community-acquired pneumonia (CAP) include ampicillin-sulbactam as an initial treatment option, though they do not mandate routine coverage of anaerobic organisms. This study aimed to compare the effectiveness of ampicillin-sulbactam with that of ceftriaxone as initial treatment for CAP in older adults.

METHODS

This study was conducted using the target trial emulation framework, using a nationwide Japanese database (May 2010-June 2023). The study included patients aged ≥65 years, admitted to Diagnosis Procedure Combination hospitals for CAP, who received either ampicillin-sulbactam or ceftriaxone as the initial treatment. The exposure group received ampicillin-sulbactam, while the control group received ceftriaxone, both on the day of hospitalization. The primary outcome was in-hospital mortality; the secondary outcome was the development of infection during hospitalization.

RESULTS

The study included 26 633 older patients hospitalized with CAP, with 14 906 receiving ampicillin-sulbactam and 11 727 receiving ceftriaxone as initial treatment. After inverse probability of treatment weighting, the ampicillin-sulbactam group was associated with a higher in-hospital mortality rate than the ceftriaxone group (10.5% vs 9.0%, respectively; adjusted risk difference, 1.5% [95% confidence interval, .7%-2.4%]; adjusted odds ratio, 1.19 [1.08-1.31]). The incidence of infection was numerically higher in the ampicillin-sulbactam group (0.6% vs 0.4%; adjusted risk difference, 0.2% [95% confidence interval, .0%-.4%]; adjusted odds ratio, 1.45 [.99-2.11]). These results were consistent among patients with risk factors for aspiration.

CONCLUSIONS

In older patients with CAP, initial treatment with ampicillin-sulbactam was associated with higher mortality compared to treatment with ceftriaxone.