Infection is a key determinant of morbidity in patients with pancreatic walled-off necrosis (WON), yet data on microbial characteristics and the effectiveness of antibiotic regimens remain insufficiently described. This study aimed to characterize the microbial flora of WON at the index intervention and to evaluate its association with clinical outcomes.

We retrospectively included consecutive patients with WON who underwent endoscopic ultrasound (EUS)-guided transmural drainage between 2010 and 2024 at a tertiary referral center. The index intervention was defined as the first drainage procedure during which fluid/pus was obtained for microbiological culture. Patients were excluded from the analysis if microbiological sampling could not be performed at the index intervention (e.g. due to inaccessibility of the necrotic cavity).

Primary endpoints were the microbial flora and its association with mortality, ICU admission, and length of stay (LOS). Secondary endpoints included microbial susceptibility to empiric antibiotic regimens and the predictive value of C-reactive protein (CRP) and white blood cell count (WBC). Infected necrosis was defined by positive bacterial or fungal cultures; sterile necrosis by negative cultures.

Of 345 patients with WON, 300 were eligible for analysis. Culture-positive infection was identified in 251 patients (83.7%), most often polymicrobial (65%). The predominant pathogens were Enterococcus faecium (47%), Escherichia coli (20%), and Candida albicans (22%). Patients with infected necrosis had higher rates of ICU admission (35.1% vs. 18.4%; OR 2.39, p=0.020), with no statistically significant difference in mortality (10.4% vs. 2.0%; OR 5.55, p=0.096) and LOS (median 79 days (IQR; 56–109.5) vs. 76 days (IQR; 65–116); OR 1.21, 95% CI 0.66–2.24; p=0.64). Despite antibiotic use in 240 patients (80%) before sampling, infection remained highly prevalent, and infected necrosis was more common among those receiving antibiotics compared with those who did not (86.3% vs. 73.3%; p=0.026). Of 518 organisms isolated, only 35.5% were susceptible to administered antibiotics or antifungals prior to intervention. Both CRP and WBC were independently associated with infection (OR per 10 mg/L CRP 1.05, 95% CI 1.02–1.09; OR per 1×10⁹/L WBC 1.09, 95% CI 1.03–1.16), although discriminatory performance was modest (AUC ≤0.66).

Infection in WON is mostly polymicrobial and associated with prolonged ICU admission.