Prophylactic Antibiotics in Severe Acute Pancreatitis

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Prophylactic Antibiotics in Severe Acute
Pancreatitis
Dr Neil Orford Intensive Care Unit The Geelong
Hospital
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Introduction

• Acute pancreatitis spectrum of disease
• mild, self-limiting disease requiring brief
  hospitalisation
• Rapidly progressive, fulminant illness resulting
  in multi-organ failure, with mortality of 30-50,
  months in hospital

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Management

• Resuscitation
• Analgesia
• Investigation
• Enteral nutrition
• ERCP
• Surgery
• Pharmacological agents
• Supportive
• Prophylactic antibiotics

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Prophylactic Antibiotics

• Infection of necrotic tissue occurs 30-70 pts
  with pancreatic necrosis, associated increase
  mortality.
• Infected necrosis may be more common if biliary
  origin
• Majority infections develop 1st 4 weeks, peak
  week 2,3.

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Prophylactic Antibiotics

• Experimental theory bacterial translocation from
  colon
• Polymicrobial enterobacter, staph, enterococci,
  streptococci, anaerobes, pseudomonas,
  acinetobacter, candida.
• Candida spp. More common SAP, use of broad
  spectrum antibiotics. Incidence up to 30 of
  necrotising pancreatitis, associated higher
  mortality.

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Intravenous Prophylaxis

• Rat model I.V imipenem or ciprofloxacin reduce
  infections and death, also possible role of SD.
• Humans retrospective, 180 pts
• mortality infection
• no prophylaxis 16 76
• I.V imipenem 5 27.
• Not stat significant.
• 14 yr study, poor methodology

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Intravenous Prophylaxis

• Numerous meta-analysis, conflicting, inconsistent
  results
• Concerns regarding increase reporting gram
  positive and fungal infections in setting of
  prophylaxis

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Pubmed

• Search terms prophylaxis, antibiotics, severe
  acute pancreatitis
• 15 results
• 9 prospective trials abs

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Early antibiotic treatment in acute necrotising
pancreatitis

• Sainio V, Kemppainen E, et al.
• Lancet 1995, 346 663-664
• Prospective, RCT
• Cefuroxime 1.5g tds vs placebo
• Antibiotics commenced if infection clinically
• 60 pts with necrotising alcohol induced SAP
• Mortality decreased with prophylaxis 1 vs 7
  deaths
• All due to decreased UTIs
• Problems
• Not randomised, blinded
• High rate UTIs, responsible for difference

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Controlled clinical trial of pefloxacin vs
imipenem in severe acute pancreatitis

• Bassi C, Falconi M, Talamini G
• Liver, Pancreas, and Biliary Tract
• Gastroenterology 1998 1151513-1517
• 60 pts necrotising pancreatitis (gt50)
• Randomised 2 weeks imipenem 500mg tds vs
  pefloxacin 400 mg bd
• 50 patients biliary origin
• All received TPN
• Lower pancreatic infeciton rate with imipenem
  (10 vs 34)
• Deaths all due to septic shock, all
  multi-resistant organisms

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Prophylactic antibiotics in treatment of severe
acute alcoholic pancreatitis

• Delcenserie R, Yzet T, Ducroix JP.
• Pancreas 1996 Aug 13(2)198-201
• 23 consecutive pts acute alcoholic pancreatitis
  with CT evidence fluid collections
• Ceftazidime / amikacine / flagyl vs placebo
• 10 days
• Outcome severe sepsis 0 vs 7

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Early antibiotic treatment of septic
complications in SANP a prospective, randomised,
multicener study comparing two regimens with
imipenem-cilastin

• Maravi-Poma E, Gener J, etal
• Intensive Care Medicine
• 2003 291974-1980
• 92 pts with SANP
• Imipenem 500mg QID for 14/7 or until resolution
  systemic illness
• Resistant organisms

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Prophylaxis with meropenem of septic
complications in acute pancreatitis A RCT versus
imipenem

• Manes G, Rabbitti P, etal
• Pancreas 2003 Nov 27(4) e79-83
• 176 pts SANP
• Randomised meropenem 0.5g tds vs imipenem 0.5g
  qid
• No difference in outcome

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Prophylactic antibiotic treatment in patients
with predicted severe acute pancreatitis a
placebo-controlled, double blind trial

• Isenmann R, Runzi M, et al
• Gastroenterology
• 2004 Apr 126 (4)997-1004
• Planned sample size 200 pts with SAP
• 1st blinded study
• Iv cipro 400mg bd flagyl 500mg bd vs placebo
• Open antibiotic use if infectious complication,
  multiorgan failure, sepsis

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Prophylactic antibiotic treatment in patients
with predicted severe acute pancreatitis a
placebo-controlled, double blind trial

• 114 pts enrolled
• Trial stopped at interim analysis for lack of
  benefit

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Early antibiotic treatment for severe acute
necrotising pancreatitis

• Dellinger E, Tellado J, et al.
• Annals of Surgery 2007 245 (5) 674-683
• 32 centres
• Randomised, double-blind, placebo controlled
  prospective
• Inclusion SAP
• Contrast CT gt30 necrosis
• Unsuitable for contrast - multiple
  peripancreatic fluid collections and edema and
  raised CRP or MODs
• Meropenem 1g tds vs placebo 7-21 days
• 100 pts enrolled over 22 months

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Early antibiotic treatment for severe acute
necrotising pancreatitis
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Summary to 2007

• Severe acute necrotising pancreatitis
• CT proven gt50
• Some evidence of mortality benefit with
  prophylaxis but
• Small numbers in trial
• Some negative results
• 1 study high incidence UTIs
• 1 study high incidence biliary obstruction /ERCP
• 2 recent double blind RCTs show no benefit with
  prophylaxis
• Current practice BH give meropenem all SAP (not
  just necrotising)

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Discussion

• Acute Severe Pancreatitis
• Prophylaxis
• meropenem 500mg qid 14/7
• Necrotising or all?
• vs
• On-demand
• New SIRS / sepsis
• Newly developed 2 or more organ failures
• Proven infection

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Surgery

• Controversial.
• 10 minute discussion of surgical management
  acute pancreatitis should include 9 minutes of
  silence (1972)