Introduction: Prompt antibiotic administration is essential in the management of acute cholangitis (AC). In selecting initial antibiotics, it is important to consider both the severity of the condition and the antimicrobial activity spectrum, particularly against major resistant bacteria. Extended-spectrum β-lactamases and AmpC productions are key factors in pathogen resistance; however, knowledge of patient characteristics in cholangitis management remains limited. We aimed to analyze risk factors for extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and for chromosomally mediated AmpC-producing Enterobacteriaceae (CAE). Methods: This study retrospectively analyzed patients with AC who underwent endoscopic retrograde cholangiopancreatography (ERCP) at a tertiary center in Japan between April 1, 2018, and April 30, 2024. This analysis focused on evaluating the first episode of AC during hospitalization. Results: A total of 721 patients with cholangitis underwent ERCP. ESBL-E was detected as the causative pathogen in 22 cases, whereas CAE was identified in 113 cases. Patients with CAE experienced a significantly higher recurrence rate within 60 days (15.9% vs. 4.3%, p < 0.001) and required more frequent escalation to broad-spectrum antibiotics (19.5% vs. 8.7%, p = 0.001). No significant differences in clinical outcomes were observed between patients with and without ESBL-E. Multivariate analysis identified independent risk factors for AC caused by ESBL-E: previous antibiotic use within 90 days, dialysis, and residence in nursing homes. For CAE, independent risk factors included antibiotic use within 90 days and a history of endoscopic sphincterotomy (EST). Conclusion: In AC, recent antibiotic use, dialysis, and institutionalization are associated with ESBL-E, whereas recent antibiotic use and a history of EST are linked to CAE.

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