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Prof. Claudio Bassi MD claudio.bassi@univr.it Surgical & Gastroenterological Department

TIROLO-VENETO-LOMBARDA e TRIVENETA di Chirurgia Pancreatite Acuta: quale antibiotico e quando? Quando la chirurgia?. Prof. Claudio Bassi MD claudio.bassi@univr.it Surgical & Gastroenterological Department University of Verona ITALY. Quando la chirurgia?. FROM FAST TRACK SURGERY…

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Prof. Claudio Bassi MD claudio.bassi@univr.it Surgical & Gastroenterological Department

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  1. TIROLO-VENETO-LOMBARDAe TRIVENETA di Chirurgia Pancreatite Acuta: quale antibiotico e quando?Quando la chirurgia? Prof. Claudio Bassi MD claudio.bassi@univr.it Surgical & Gastroenterological Department University of Verona ITALY

  2. Quando la chirurgia? FROM FAST TRACK SURGERY… …TO SLOW TRACK SURGERY!!!

  3. Pancreatite Acuta: quale antibiotico e quando?Quando la chirurgia?MANAGEMENT OF PANCREATIC NECROSIS Acute Necrotizing Pancreatitis Sterile Necrosis Infected Invasive Conservative

  4. WORLDWIDE “INVASIVE” INDICATION: INFECTED NECROSIS

  5. CLINICAL SIGNIFICANCE OF INFECTED NECROSIS 1005 patients Cavallini G et al. Dig Liv Dis, 2004; 36(3): 205-11

  6. PREVENTIONEARLY ANTIBIOTIC TREATMENT • Drugs suitable against the responsable flora • Able to penetrate the pancreas • Tested in prospective trials

  7. MICROBIOLOGICAL FINDINGS IN INFECTED NECROSIS DURING SAP E. Coli Klebsiella Staphylococco Pseudomonas Enterococco Candida Aerogenes Seratia Fragilis

  8. The haemato-pancreatic barrier

  9. Poor penetration Varying degrees Good penetration Aminoglycosides Cefoxitin Clindamycin Ampicillin Ceftazidime Fluoroquinolone Cephalosporins Chloramphenicol Imipenem Moxalactam Clotrimoxazole Metronidazole Tetracyclines Streptomycin Mezlocillin Antibiotics penetration into pancreatic tissue.

  10. CLINICAL TRIAL 90 -2008 • Tredici studi RCT • Risultati contradittori • Disomogeneità dei criteri d’ammisione • Disomogeneità delle interpretazioni • Basso potere statistico … • Ergo !!! Via la “festival delle metanalisi!!!

  11. The “festival” of meta-analyses

  12. Poor penetration Varying degrees Good penetration Aminoglycosides Cefoxitin Clindamycin Ampicillin Ceftazidime Mezlocillin Cephalosporins Chloramphenicol Moxalactam Clotrimoxazole Metronidazole Tetracyclines Quinolone Imipenem QUALCOSA SFUGGE! Antibiotics penetration into pancreatic tissue

  13. Mortality Cochrane Library, 2006, Issue 4

  14. Infected pancreatic necrosis Cochrane Library, 2006, Issue 4

  15. Operative treatment Cochrane Library, 2006, Issue 4

  16. Non pancreatic infections Cochrane Library, 2006, Issue 4

  17. BETALACTAM? DANGER !!! The ineluctability of a similar choice • Resistant strains • Fungal Infection

  18. MORTALITY RATE BY CANDIDA IN SAP P=0.0001 Gotzinger P. et al. Shock 2000;14(3): 320-3

  19. A not negligible reality Pancreatic infection in severe pancreatitis. The role of fungus and multiresistant organisms. Gloor B, et al. Arch Surg 2001; 136: 592-6 Prophylactic alter the bacteriology of infected necrosis in severe acute pancreatitis. Howard TJ, Temple MB. J Am Coll Surg. 2002; 195(6): 759-67 Emergence of antibiotic resistance in infected pancreatic necrosis. De Waele JJ, et al. Arch Surg 2004; 139: 1371-5

  20. But … Fungal infection Cochrane Library, 2006, Issue 4

  21. The “festival” of meta-analyses

  22. Severe Acute Pancreatitis Betalactams use • Reduces infectious complications • Reduces mortality • but..... .... CAVEAT!!! • Resistant species • Nosocomial infections • Fungal infections Kivilaakso, Bern, 1997

  23. How to come out? • Reducing treatment time?

  24. Severe Acute Pancreatitis Fungal infection vs Imipemen therapy duration (17 pts) (11 pts) (5 pts) Gloor B et al. Arch Surg, 2001;136: 592-6

  25. Severe Acute Pancreatitis Imipemen (500 mg X 4/day) for 14 days vs >14 days (46 pts) (46 pts) • Maravi-Poma E et al. Intensive Care Med 2003; 29(11):1974-80

  26. The blanket is always short!

  27. How to come out? • Betalactams plus fungal prophylaxis?

  28. Severe Acute Pancreatitis Fungal Infection and Antimicotic Prophylaxis * (100 mg/die) *p<0.01 vs control He YM et al World J Gastroenterol 2003;9(11): 2619-21

  29. How to come out? TORNIAMO AI “QUANDO” • Betalactam prophylaxis • Fungal prophylaxis • Performing surgery at the right time Selecting the “right” population

  30. 0 2 4 5 6 7 8 9 10 1 3 Mortality: 17% Morbility: 92% Mortality: 3% Morbility: 8% Mortality: 6% Morbility: 35% PROGNOSTIC FACTORS FROM C.T. SEVERITY INDEX(Balthazar, Radiology, 1994) ?

  31. Doctors giving Thanks to Influenza, by James West, 1803 WE NEED FUTURE ALTERNATIVES!!!

  32. Role of early enteral feeding in SAP • EN stimulates mucosa perfusion • EN inhibits increases in permeability • EN preserves production of IgA • EN stimulates enterohepatic circulation FINAL EFFECT EN decrease colonic bacterial translocation and preserves probiotic bacteria.

  33. clinical efficacy (with good compliance and low toxicity) echological impact economical impact The three cornerstones for a proper choice of antibiotic therapy and Surgery in SAP

  34. THANK YOU ALL!!!

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