Association Between Ceftriaxone Use and Biliary Infections in Patients With Pneumonia: A Nationwide Retrospective...

Ceftriaxone is believed to increase the risk of biliary infections due to pseudolithiasis caused by ceftriaxone-calcium precipitation, but this risk is not well understood. This study aimed to investigate whether ceftriaxone use is associated with an increased risk of biliary infections in pneumonia patients using a national inpatient database.

We analyzed the Diagnosis Procedure Combination database in Japan, identifying pneumonia patients between July 2010 and March 2022. Patients were grouped by treatment: ceftriaxone versus ampicillin-sulbactam or cefotaxime. Propensity score overlap-weighting was used to adjust for confounding factors. The primary outcome was a composite measure, including cholecystitis or cholangitis during hospitalization, and any percutaneous, endoscopic, or surgical interventions on the biliary tract. Secondary outcomes included individual components of the primary outcome.

Of the 1 503 885 eligible patients, 558 725 received ceftriaxone, while 945 160 were treated with either ampicillin-sulbactam or cefotaxime. The mean dose of ceftriaxone was 1.7 g/day (standard deviation, 0.7 g/day), with a mean administration duration of 7.1 days (standard deviation, 3.8 days). Propensity score overlap-weighting analysis revealed that ceftriaxone treatment was associated with an increased incidence of the composite outcome (0.22% vs. 0.18%; risk difference, 0.05%; 95% confidence interval, 0.03%-0.07%; p < 0.001), as well as the secondary outcomes, including cholecystitis or cholangitis during hospitalization and percutaneous or endoscopic drainage of the gallbladder or biliary tract.

Ceftriaxone use was associated with a slight increase in the risk of biliary infections.