EUS-guided biliary drainage (EUS-BD) is increasingly used for malignant and benign obstruction when ERCP is unsuccessful or not feasible. Due to tract creation and larger stent systems, EUS-BD represents a more invasive endoscopic intervention, potentially increasing the risk of bacteremia and the frequency of infectious complications. We aimed to evaluate the prognostic role of positive index bile cultures for predicting post-interventional infectious morbidity and infection-driven re-interventions.

We performed a retrospective single-center cohort of 227 patients undergoing EUS-guided hepaticogastrostomy or other EUS-guided biliary drainage between March 2020 and March 2025 at our tertiary endoscopy center. Index bile aspirates were classified as positive or non-positive. At our center, bile microbiology sampling is routinely performed in all patients during EUS-BD interventions before stent deployment. Primary endpoints included a 30-day infectious adverse event, notably post-drainage cholangitis, graded by the Tokyo Guidelines. Secondary endpoints were the rate of infection-driven reinterventions within 6 months and mortality.

Positive index bile cultures obtained at the time of EUS-guided biliary drainage were found in 62 of 227 patients (27.3%). Patients with culture-positive bile had significantly higher rates of 30-day infectious adverse events compared with non-positive cases (30.6% vs. 8.3%, p < 0.001), and more frequent acute cholangitis recurrence within 90 days (17.7% vs. 4.2%, p < 0.001). A positive index bile culture also translated into increased infection-driven reintervention during 6-month follow-up (29.0% of culture-positive vs. 5.0% of non-positive patients, p < 0.001), typically managed by restenting through the existing stent lumen when purulent stent occlusion or clinical sepsis signs developed. Most cultured pathogens were MDR gram-negative Enterobacteriaceae. Bile microbiology taken at the index EUS‑BD allowed early infection-risk recognition, directly guiding adverse events grading, antibiotic choice, and close 6-month follow-up intensity. In patients with culture-positive index bile, early infectious adverse events were significantly more frequent after hepaticogastrostomy than after other EUS-guided biliary drainage techniques (48.4% vs. 12.9%, p < 0.001), supporting that, in the presence of infected bile, the hepaticogastrostomy pathway is associated with greater early infectious activity, likely related to transluminal tract creation.

In this real-world cohort, positive bile culture obtained at the index EUS-BD session was strongly associated with early infectious adverse events and a high risk of infection rebound requiring subsequent reintervention for acute cholangitis. Index biliary microbiology provides a practical assessment of infection risk, but negative cultures do not exclude severe or fatal biliary sepsis.