Comparison of effectiveness and safety of cefoperazone–sulbactam versus ceftriaxone and flomoxef in acute cholangitis: a multicenter retrospective study

ABSTRACT Acute cholangitis is a potentially life-threatening biliary tract infection requiring prompt antibiotic therapy. Cefoperazone–sulbactam is a recommended option for mild-to-moderate disease, but comparative evidence versus ceftriaxone and flomoxef is limited. In this multicenter retrospective study, 389 adults with acute cholangitis from nine Taiwanese centers (January 2022–July 2024) received cefoperazone–sulbactam ( n = 249), ceftriaxone ( n = 37), or flomoxef ( n = 103). The primary outcome was clinical response (cure or improvement) on days 4, 7, and 14. Secondary outcomes were microbiological response, in-hospital mortality, and adverse events (AEs). Multivariable logistic regression was performed, adjusting for age, sex, biliary stenting, comorbidities, malignancy, disease severity, and timing of biliary drainage. Baseline characteristics were similar across groups (mean age, 67 years; 91.8% had mild-to-moderate disease; 33.2% had bacteremia). Day 4 clinical response rates were 96.8% with cefoperazone–sulbactam, 97.3% with ceftriaxone, and 93.2% with flomoxef ( P = 0.05). Day 7 response did not differ significantly. Compared with cefoperazone–sulbactam, the adjusted odds ratio for day 4 clinical response was 1.40 (95% confidence interval [CI]: 0.17–11.78) for ceftriaxone and 0.50 (95% CI: 0.18–1.43) for flomoxef. AEs were uncommon (2%–5%), mostly mild and not associated with sequelae. Cefoperazone–sulbactam appears to be an effective and safe empiric therapy for acute cholangitis in real-world practice, with high observed early clinical response rates. Although outcomes were statistically similar to those of ceftriaxone and flomoxef, the underpowered between-group comparisons preclude definitive conclusions regarding comparative efficacy. These findings support its continued clinical use while awaiting confirmation in larger randomized trials.