Controversies of Antibiotics in Acute Severe Pancreatitis

1. Antibiotics in Acute Pancreatitis
Dr Palepu B Gopal

3. Pancreatitis
• Inflammation in pancreas with injury to
exocrine pancreas

5. Clinical
outcome

6. Etiology
Philip V et al. Clin Gastroenterol Hepatol 2011;152:573-8

8. Gall stone pancreatitis Alcoholic pancreatitis

9. Severity
The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218

13. SAP IPN

14. PROPHYLACTIC ANTIBIOTICS
Mortality in Pancreatitis :are antibiotics protective

15. Historically
• In 1970s clinical trials showed no benefit of
prophylactic antibiotics. WHY?
– Ampicillin was the most commonly used drug in these
studies .
– Failed to reach minimal inhibitory concentration in
Pancreatic tissue

16. • N=74 with pancreatic necrosis on CT scan
within 72 hours of onset
• Randomized:
– Imipenem for 14 days or no antibiotics
RESULTS:
• Less Pancreatic Sepsis in Antibiotic arm
• 12.2% vs 30.3% (p<0.01)
A randomized multicenter clinical trial of antibiotic prophylaxis of septic
complications in acute necrotizing pancreatitis with imipenem.
Pederzoli P, Bassi C, Vesentini S, Campedelli A.
Surg Gynecol Obstet. 1993 May;176(5):480-3.

17. Before 2000

18. Prophylactic antibiotic treatment in patients with predicted severe acute
pancreatitis: a placebo-controlled, double-blind trial.
Isenmann R1, German Antibiotics in Severe Acute Pancreatitis Study
Group.
Gastroenterology.2004 Apr;126(4):997-1004.
RESULTS:
• Fifty-eight patients received Ciprofloxacin/Metronidazole and 56 patients Placebo.
• 28% in the Ciprofloxacin/Metronidazole group required open antibiotic treatment
vs. 46% with Placebo.
• 12% of the Ciprofloxacin/Metronidazole group developed infected pancreatic
necrosis compared with 9% of the Placebo group (P = 0.585).
• Mortality was 5% in the Ciprofloxacin/Metronidazole and 7% in the Placebo group.
• In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no
differences in the rate of infected pancreatic necrosis, systemic complications, or
mortality were observed.
CONCLUSIONS:
• This study detected no benefit of antibiotic prophylaxis with respect to the risk of
developing infected pancreatic necrosis
Limitation Under powered study aimed to study 240 patients

20. change

21. 14 trials ;841 patients
Systematic review and meta-analysis of antibiotic
prophylaxis in severe acute pancreatitis
Mathias Wittau et al. Scandinavian Journal of Gastroenterology, 2011

22. Systematic review and meta-analysis of antibiotic
prophylaxis in severe acute pancreatitis
Mathias Wittau et al. Scandinavian Journal of Gastroenterology, 2011
Design Total 14 trials with 841 patients
Results Use of antibiotic prophylaxis was NOT associated with :
reduction in mortality (RR 0.74 [95% CI 0.50 – 1.07])
incidence of infected pancreatic necrosis (RR 0.78 [95% CI 0.60–1.02])
incidence of nonpancreatic infections (RR 0.70 [95% CI 0.46–1.06])
incidence surgical interventions (RR 0.93 [95% CI 0.72–1.20])
Conclusion There is no evidence that supports the routine use of
antibiotic prophylaxis in patients with SAP.

23. RR of mortality rate : 0.77 to 1.00 with narrow confidence interval (P < 0.05)
NNT having a minor lower limit of the range (7-5096 patients)
Certain SAP patients could still potentially prevent death by antibiotic prophylaxis

24. Early prophylactic antibiotics administration for acute
Necrotizing pancreatitis: a meta-analysis of randomized
controlled trials. Tomohiko Ukai et al. J Hepatobiliary Pancreat Sci.2015
Six Studies between 1993-2009 with 397 pts
Imipenam, Cefuroxime & Ciprofloxacillin

25. MM Mourad et al. Ann R Coll Surg Engl 2017
 Mixed evidence found to support and refute the role of prophylactic antibiotics in AP
 Most studies have failed to demonstrate much benefit from its routine use
 Data from our unit little benefit of their routine use
mortality & Morbidity was significantly higher in AB group
 Antibiotics should be used in patients who develop sepsis
infected necrosis-related SIRS
MODS or pancreatic and extra-pancreatic infection
 Prompt antibiotics once inflammatory markers are raised
to prevent secondary pancreatic infection.

26. 2013 Guidelines
2018 Guidelines update

27. EARLIEST
Most commonly involved organ

28. BETA LACTAM VS CONTROL

29. Beta Lactam vs Control

30. The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218

33. Take home messages
• No role of prophylactic antibiotics and antifungals in acute
severe pancreatitis
• Infected pancreatic necrosis obtain cultures by CT guided
FNA and start empiric or culture guided antibiotics
• Select antibiotic depending on its penetration to pancreatic
tissue
• No role of probiotics
• Antibiotics should be given for all extra pancreatic
infections
• Procalcitonin can help in predicting SAP
• APACHE II is the best severity scoring tool for acute
pancreatitis and BISAP is comparable to APACHE II