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