Gut Microbiome

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

TL;DR

Gastrointestinal Enterococcus colonization was associated with subsequent infected necrosis in acute necrotizing pancreatitis, typically preceding clinical diagnosis by 3 weeks, and early antibiotic use was associated with both Enterococcus colonization and infected necrosis.

Key Findings

Rectal Enterococcus colonization was associated with subsequent development of infected necrosis in necrotizing pancreatitis.

  • Adjusted hazard ratio for rectal Enterococcus colonization and infected necrosis was 4.48 (95% CI 1.51–13.28)
  • Adjustment was made for baseline disease severity, biliary etiology, and prior antibiotic exposure
  • Results were similar when adjusting for early extra-pancreatic infection instead of disease severity
  • Study included 57 patients with necrotizing pancreatitis from the POEMA cohort across 20 Dutch hospitals

Salivary Enterococcus colonization was also associated with subsequent infected necrosis, with a higher hazard ratio than rectal colonization.

  • Adjusted hazard ratio for salivary Enterococcus colonization and infected necrosis was 5.37 (95% CI 1.72–16.79)
  • Both rectal and salivary sampling were performed twice weekly for 30 days
  • Samples were analyzed using 16S rRNA sequencing
  • The salivary association was similarly adjusted for baseline disease severity, biliary etiology, and prior antibiotic exposure

Enterococcus colonization typically preceded clinical diagnosis of infected necrosis by approximately 3 weeks.

  • The lead time between Enterococcus colonization and clinical diagnosis of infected necrosis was typically 3 weeks
  • 20 of 57 patients (35%) with necrotizing pancreatitis developed infected necrosis
  • Colonization developed during admission rather than being present at baseline
  • Colonization occurred predominantly in the first 2 weeks of admission

Early antibiotic use was associated with Enterococcus colonization in the gastrointestinal tract.

  • Early antibiotic use was associated with Enterococcus colonization with an adjusted HR of 4.99 (95% CI 1.57–15.80)
  • 40% of early antibiotic use occurred without a documented infection
  • Early antibiotic use was also associated with reduced butyrate-producer abundance in the gut microbiota
  • These associations suggest a potential mechanism linking antibiotic-driven dysbiosis to subsequent infection

Early antibiotic use was associated with subsequent development of infected necrosis.

  • Adjusted hazard ratio for early antibiotic use and infected necrosis was 3.56 (95% CI 1.23–10.28)
  • 40% of patients receiving early antibiotics had no documented infection at the time of antibiotic administration
  • The authors note that whether this relationship is causal warrants further investigation
  • Authors suggest that if confirmed, findings would warrant a more restrictive antibiotic policy in early acute pancreatitis

Infected necrosis complicated 35% of necrotizing pancreatitis cases in this cohort, consistent with known epidemiology.

  • 20 of 57 patients with necrotizing pancreatitis developed infected necrosis (35%)
  • The broader literature cited in the abstract reports infected necrosis complicates 30% of necrotizing pancreatitis cases
  • The POEMA cohort comprised 276 patients with acute pancreatitis across 20 Dutch hospitals, of whom 57 had necrotizing pancreatitis
  • Intestinal bacterial translocation is described as the presumed mechanism for infected necrosis

The study design involved prospective twice-weekly microbiota sampling from rectal and salivary sites for 30 days using 16S rRNA sequencing.

  • This was a predefined subgroup analysis of the POEMA cohort, a prospective multicenter microbiota study
  • Sampling was performed twice weekly for 30 days
  • Both rectal and salivary samples were collected to capture gut and upper gastrointestinal microbiota
  • 16S rRNA sequencing was used for microbiota analysis
  • Study spanned 20 Dutch hospitals

What This Means

This research suggests that a specific type of bacteria called Enterococcus, when it expands in the gut and mouth of patients with severe pancreatitis, is a warning sign that a dangerous complication called infected pancreatic necrosis may be developing. In patients whose pancreas tissue was dying (necrotizing pancreatitis), those who developed high levels of Enterococcus bacteria in their gut or saliva were roughly 4–5 times more likely to later develop infected necrosis — and this bacterial overgrowth appeared about 3 weeks before doctors could diagnose the infection clinically. Notably, this bacterial expansion was not present when patients first arrived at the hospital but developed during their stay, mostly in the first two weeks. The study also found that giving antibiotics early in the course of pancreatitis — which happened without any confirmed infection in 40% of cases — was strongly linked to both the rise of Enterococcus in the gut and the later development of infected necrosis. Early antibiotic use was also associated with a drop in beneficial bacteria that produce butyrate, a compound important for gut health. This suggests that antibiotics may disrupt the normal gut bacterial community in ways that allow harmful Enterococcus bacteria to take over, potentially increasing the risk of serious infection. This research suggests that routine early use of antibiotics in pancreatitis patients without confirmed infection may do more harm than good by disrupting the gut microbiome and potentially promoting dangerous bacterial overgrowth. The authors caution that while these associations are striking, it remains to be proven that antibiotic use directly causes these outcomes, and they call for a more cautious approach to prescribing antibiotics early in acute pancreatitis until further research confirms these findings.

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Citation

van den Berg F, Pauw H, Timmerhuis H, Besselink M, Issa Y, Bruno M, et al.. (2026). Antibiotic-associated Enterococcus expansion in the gastrointestinal tract precedes infected necrosis in acute necrotizing pancreatitis.. Gut microbes. https://doi.org/10.1080/19490976.2026.2670039