Antibiotic-associated Enterococcus expansion in the gastrointestinal tract precedes infected necrosis in acute necrotizing pancreatitis

Abstract

Infected pancreatic necrosis complicates 30% of necrotizing pancreatitis cases, with intestinal bacterial translocation as the presumed mechanism. To characterize gastrointestinal microbiota dynamics preceding infection, we performed a predefined subgroup analysis of the POEMA cohort, a prospective multicenter microbiota study across 20 Dutch hospitals. Of 276 patients with acute pancreatitis, 57 with necrotizing pancreatitis underwent twice-weekly rectal and salivary sampling for 30 d, analyzed using 16S rRNA sequencing. Twenty (35%) developed infected necrosis. After adjustment for baseline disease severity, biliary etiology, and prior antibiotic exposure, gastrointestinal Enterococcus colonization was associated with subsequent infected necrosis (rectal HR 4.48, 95% CI 1.51-13.28; salivary HR 5.37, 95% CI 1.72-16.79), typically preceding clinical diagnosis by 3 weeks; results were similar when adjusting for early extra-pancreatic infection instead of disease severity. Enterococcus colonization developed during admission, predominantly in the first 2 weeks, rather than being present at baseline. Early antibiotic use-without documented infection in 40%-was associated with Enterococcus colonisation (HR 4.99, 95% CI 1.57-15.80), reduced butyrate-producer abundance, and infected necrosis (HR 3.56, 95% CI 1.23-10.28). Whether this relationship is causal warrants further investigation, but if confirmed, it would warrant a more restrictive antibiotic policy in early acute pancreatitis.