Introduction: Although antibiotic treatment is one of the cornerstones of management of (suspected) infected necrotizing pancreatitis, indication, timing, duration and the type of antimicrobial regimes is still debated and vary. Methods: We performed a post-hoc analysis of a prospective multicenter cohort of 449 patients with necrotizing pancreatitis treated in 15 Dutch hospitals (2010 to 2019). Results on microbiological cultures and antimicrobial therapy were analysed. Results: Antimicrobial therapy was started in 369 (82%) of all patients with necrotizing pancreatitis, after a median of 5 (P25-P75: 1 – 14) days after admission. In 224/369 (70%) patients, the first antimicrobial therapy was started without a confirmed infection. Although carbapenems, specifically meropenem (n=75, 29%), were most frequently used as empirical antimicrobial therapy, Enterococcus faecium (which is intrinsically resistant to carbapenems) was frequently (24%) cultured in infected pancreatic necrosis. Multidrug-resistant bacteria were rare in the initial culture sample (2%), but increased to 14% in subsequent cultures. Empirical antimicrobial therapy started before the positive culture was appropriate in 64/128 patients (50%) with a positive pancreatic culture. In 87% of the patients with a culture that contained (partial) resistant bacteria the antibiotic regime was adjusted appropriately. Conclusion: In daily clinical practice, antimicrobial therapy are started early during necrotizing pancreatitis, mostly without a confirmed infection. E. faecium was the most frequently cultured microbe. Based on bacterial resistance and yeast involvement, empirically administered antibiotics often turn out inappropriate. Optimization of antimicrobial therapy has the potential to reduce unnecessary antibiotic use while improving clinical outcomes of patients with (infected) necrotizing pancreatitis.

Introduction: Perforation and fistula of the gastrointestinal (GI)-tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes and treatment are lacking. Methods: We performed a post-hoc analysis of 896 patients with necrotizing pancreatitis, prospectively included in 23 Dutch hospitals (2005-2015). Multivariable logistic regression was used to explore risk factors and to adjust for confounders in comparing clinical outcomes of patients with or without perforation and fistula of the GI-tract. Results: GI-tract perforations and fistulas were identified in 139 (16%) patients, mostly in the duodenum (40%) and colon (64%). Independent risk factors were highest C-reactive protein within 48-hours after admission (OR 1.20 [95%-CI 1.02–1.41]), organ-failure in the first week (OR 2.81 [95%-CI 1.80–4.39]) and infected necrosis before diagnosis (OR 1.81 [95%-CI 1.11–2.97]). GI-tract perforation and fistula were associated with poor clinical outcomes, especially when the colon was affected. This is exemplified by an increase in prolonged ICU-stays (OR 6.64 [95%-CI 13.02–15.18]) and more invasive interventions (OR 4.54 [95%-CI 1.82-13.19]). Perforations and fistulas of the stomach and duodenum were treated conservatively in 66% and surgically in 8%. Colon perforations and fistulas were treated conservatively in 27% and surgically in 57%. Conclusions: Perforations and fistulas of the GI-tract occur in one in six patients with necrotizing pancreatitis and poorly affects clinical outcomes, especially colon perforations and fistulas. Risk factors are C-reactive protein within 48 hours, early organ-failure and infected necrosis. Overall, more than half of the patients are treated conservatively.

Aims Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (rNSAIDs) administration is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration may further reduce this risk. Guidelines already recommend aggressive hydration. However, multicentre randomised trials studying the added value of aggressive hydration in patients receiving prophylactic rNSAIDs are lacking. We, therefore, performed a trial to investigate the combination of aggressive hydration and rNSAIDs.

Aims The endoscopic step-approach is preferred over a surgical step-up approach in eligible patients with infected necrotizing pancreatitis. Lumen-apposing metal stents (LAMS) might optimize endoscopic drainage and reduce the need for endoscopic necrosectomy. Nevertheless, some safety concerns, particularly bleeding, remain. We conducted a multicenter prospective study to investigate the clinical outcome of LAMS in patients with infected necrotizing pancreatitis.

BACKGROUND Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).