This study aims to evaluate the clinical outcomes of ampicillin-sulbactam versus third-generation cephalosporins (e.g., ceftriaxone or cefotaxime) in managing aspiration pneumonia.

We utilized the Diagnosis Procedure Combination (DPC) database, a comprehensive national inpatient database in Japan, to identify patients diagnosed with aspiration pneumonia between July 2010 and March 2022. Patients were categorized into two groups based on their treatment: those receiving ampicillin-sulbactam and those receiving third-generation cephalosporins (either ceftriaxone or cefotaxime). To mitigate confounding factors, propensity score overlap weighting analysis was employed to compare in-hospital mortality rates and the incidence of Clostridioides difficile infection between the two treatment groups.

Among the 548,972 eligible patients, 424,446 received ampicillin-sulbactam, while 124,526 were treated with third-generation cephalosporins. In the third-generation cephalosporin group, 97.7 % of patients were administered ceftriaxone, and 2.3 % received cefotaxime. The mean treatment duration was 8.5 days (standard deviation [SD] 4.3) in the ampicillin-sulbactam group and 7.9 days (SD 4.1) in the third-generation cephalosporin group. Propensity score overlap weighting analysis revealed that patients treated with ampicillin-sulbactam had significantly lower in-hospital mortality (14.6 % vs. 16.4 %; risk difference [RD], −1.8 %; 95 % confidence interval [CI], −2.1 % to −1.5 %; P <  0.001) and a lower incidence of C. difficile infection (2.0 % vs. 2.8 %; RD, −0.8 %; 95 % CI, −0.9 % to −0.7 %; P  <  0.001) compared to those treated with third-generation cephalosporins.

Our findings suggest that ampicillin-sulbactam was associated with lower in-hospital mortality and a reduced incidence of C. difficile infection compared to third-generation cephalosporins in patients with aspiration pneumonia.