Multidrug-resistant (MDR) pathogens may compromise empiric therapy in acute cholangitis, particularly after repeated biliary interventions. We aimed to describe MDR   prevalence   and   identify   patient-   and   procedure-related   risk   factors.

We prospectively analysed 1960 Tokyo Guideline–defined acute cholangitis episodes in a multicenter cohort. Bile and blood isolates were classified as MDR if non-susceptible to ≥1 agent in ≥3 antimicrobial classes; episodes were   labelled  MDR   when  ≥1  MDR   isolate  was   recovered.  Analyses  were restricted   to   culture-positive   episodes.

Among   979   culture-positive   episodes,   350 (35.8%) were MDR, corresponding to 17.9% of all cholangitis episodes. Patients with MDR organisms were older (mean 70.2 vs 68.0 years). MDR clustered in those with prior healthcare and biliary manipulation: previous hospitalisation increased MDR from 30.8% to 40.7%, prior ERCP from 30.1% to 46.0%, and any previous biliary stent from 30.7% to 47.5%. Stenting at the index ERCP was also associated with higher MDR rates (39.7% vs 29.5% without stent). MDR isolates accounted for 35.4% of bile and 23.3% of blood cultures. In multivariable analysis, older age (30% higher   odds   per   decade),   previous   ERCP   (adjusted   odds   ratio   [aOR]   2.4)   and   antibiotic administration   before   ERCP   (aOR   1.5)   remained   independently   associated   with   MDR.

In this large acute cholangitis cohort, over one-third of culture-positive episodes involved MDR organisms, with substantially higher rates in older patients and those with recent hospitalisation,  prior  ERCP,  and  biliary  stents.  These  findings  support  escalation  of  empiric therapy for patients with significant prior biliary manipulation or healthcare exposure, while antimicrobial-sparing   regimens   may   remain   appropriate   for   truly   community-acquired   cases without such risk factors.