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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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