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Overuse and Misuse of Antibiotics and the Clinical Consequence in Necrotizing Pancreatitis: An Observational
Hester C Timmerhuis1,2, Fons F van den Berg3,4, Paula C Noorda2
1Departments of Surgery.
Objective:
The use and impact of antibiotics and the impact of causative pathogens on clinical outcomes in a large real-world cohort covering the entire clinical spectrum of necrotizing pancreatitis remain unknown.
Summary Background Data:
International guidelines recommend broad-spectrum antibiotics in patients with suspected infected necrotizing pancreatitis. This recommendation is not based on high-level evidence and clinical effects are unknown.
Materials And Methods:
This study is a post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis in 15 Dutch centers (2010-2019). Across the patient population from the time of admission to 6 months postadmission, multivariable regression analyses were used to analyze (1) microbiological cultures and (2) antibiotic use.
Results:
Antibiotics were started in 321/401 patients (80%) administered at a median of 5 days (P25-P75: 1-13) after admission. The median duration of antibiotics was 27 days (P25-P75: 15-48). In 221/321 patients (69%) infection was not proven by cultures at the time of initiation of antibiotics. Empirical antibiotics for infected necrosis provided insufficient coverage in 64/128 patients (50%) with a pancreatic culture. Prolonged antibiotic therapy was associated with Enterococcus infection (OR 1.08 [95% CI 1.03-1.16], P =0.01). Enterococcus infection was associated with new/persistent organ failure (OR 3.08 [95% CI 1.35-7.29], P <0.01) and mortality (OR 5.78 [95% CI 1.46-38.73], P =0.03). Yeast was found in 30/147 cultures (20%).
Discussion:
In this nationwide study of patients with necrotizing pancreatitis, the vast majority received antibiotics, typically administered early in the disease course and without a proven infection. Empirical antibiotics were inappropriate based on pancreatic cultures in half the patients. Future clinical research and practice must consider antibiotic selective pressure due to prolonged therapy and coverage of Enterococcus and yeast. Improved guidelines on antimicrobial diagnostics and therapy could reduce inappropriate antibiotic use and improve clinical outcomes.
Insights
Most necrotizing pancreatitis patients receive early antibiotics without proven infection, often with inappropriate empirical coverage. Prolonged antibiotic use is linked to Enterococcus infections, organ failure, and mortality, necessitating guideline improvements.
Area of Science:
- Gastroenterology
- Infectious Diseases
- Critical Care Medicine
Background:
- International guidelines recommend broad-spectrum antibiotics for suspected infected necrotizing pancreatitis, but evidence is limited and clinical effects are unknown.
- The real-world use and impact of antibiotics and pathogens in necrotizing pancreatitis are not well understood.
Purpose of the Study:
- To investigate antibiotic use, pathogen prevalence, and their impact on clinical outcomes in a large cohort of patients with necrotizing pancreatitis.
- To evaluate the appropriateness of empirical antibiotic therapy and identify associations between specific pathogens and outcomes.
Main Methods:
- Post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis across 15 Dutch centers (2010-2019).
- Multivariable regression analyses were used to examine microbiological cultures and antibiotic use from admission to 6 months postadmission.
Main Results:
- 80% of patients received antibiotics, often initiated early (median 5 days) and without proven infection (69%).
- Empirical antibiotics showed insufficient coverage in 50% of patients with pancreatic cultures.
- Prolonged antibiotic therapy correlated with Enterococcus infection, which was associated with organ failure and mortality. Yeast was found in 20% of cultures.
Conclusions:
- The majority of necrotizing pancreatitis patients receive early antibiotics without proven infection, with high rates of inappropriate empirical coverage.
- Prolonged antibiotic use may exert selective pressure, increasing the risk of Enterococcus and yeast infections, organ failure, and mortality.
- Improved guidelines for antimicrobial diagnostics and therapy are crucial to reduce inappropriate antibiotic use and enhance clinical outcomes in necrotizing pancreatitis.
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