When critically ill patients with pancreatitis develop infection of the pancreas, the ongoing management of such patients becomes difficult. Sufficient evidence supports the use of broad-spectrum antibiotic prophylaxis to prevent the development of bacterial infection. Since fungal infection is also a relatively common complication of severe pancreatitis--particularly when broad-spectrum antibiotics are used--it seems logical that fungal prophylaxis may be an important component of management. In this issue of Critical Care, two expert groups debate the merits of antifungal prophylaxis in patients with acute necrotizing pancreatitis who are receiving antibiotics

Eggimann,  P.

Jamdar,  S.

Siriwardena,  A. K.

PubMed

Serveur académique lausannois

Page 1 of 4(page number not for citation purposes)Available online http://ccforum.com/content/10/5/229AbstractWhen critically ill patients with pancreatitis develop infection of thepancreas, the ongoing management of such patients becomesdifficult. Sufficient evidence supports the use of broad-spectrumantibiotic prophylaxis to prevent the development of bacterialinfection. Since fungal infection is also a relatively commoncomplication of severe pancreatitis – particularly when broad-spectrum antibiotics are used – it seems logical that fungalprophylaxis may be an important component of management. Inthis issue of Critical Care, two expert groups debate the merits ofantifungal prophylaxis in patients with acute necrotizingpancreatitis who are receiving antibiotics.The scenarioA 47 year old male presents to your intensive care unit withevidence of severe pancreatitis. He develops multi-organfailure, including the need for intubation/mechanicalventilation, inotropes and dialysis. Although the cause of hispancreatitis is not clear, there is evidence of pancreaticnecrosis on abdominal imaging. As a result you start broad-spectrum antibiotics and plan on-going management with thesurgical team. Given that you understand these patients areat high risk for fungal infection, you wonder about the role ofprophylactic antifungal agents.ReviewPro/con debate: Antifungal prophylaxis is important to preventfungal infection in patients with acute necrotizing pancreatitisreceiving broad-spectrum antibioticsPhilippe Eggimann1, Saurabh Jamdar2 and Ajith K Siriwardena21Department of Intensive Care Medicine and Burn Unit, Interdisciplinary Department for Support and Technics, Centre Hospitalier Universitaire Vaudois(CHUV), Lausanne, Switzerland2Hepatobiliary Surgery Unit, Department of Surgery, Manchester Royal Infirmary, Manchester, UKCorresponding author: A Siriwardena, Ajith.Siriwardena@CMMC.nhs.ukPublished: 7 September 2006 Critical Care 2006, 10:229 (doi:10.1186/cc5025)This article is online at http://ccforum.com/content/10/5/229© 2006 BioMed Central LtdPro: Antifungal prophylaxis should be parallel to any antimicrobial prophylaxisPhilippe EggimannAcute pancreatitis is severe in only 20% of patients with thedisease, but despite continuous advances in supportivetreatments, the prognosis for these patients has not improvedover the past decades. Necrosis of the pancreatic tissuedevelops early in 25% to 40% of patients, and for those whosurvive to an eventual initial multiple organ failure, mortalityrates up to 60% have been linked to the high proportion ofsuperinfections [1]. Gram-negative bacteria and fungiprogressively colonize the bowel within the first two weeks ofthe disease and further translocate into necrotic tissues [2].Bacterial and fungal infections have been documented inpatients not exposed to prior antimicrobials at rates of 40%to 70% [3] and 5% to 8% [2,4,5], respectively. Infectedpancreatic necrosis or, for some experts, a high suspicion ofit requires aggressive surgical debridement, itself associatedwith further increased morbidity and mortality [6,7].This vicious circle has prompted the testing of earlyantimicrobial prophylaxis in acute pancreatitis. The results ofat least 12 studies suggest that morbidity and mortality arereduced when prophylaxis is restricted to the most severecases. Despite considering the same data compiled inseveral meta-analyses and systematic reviews, experts andscientific organizations have drawn different conclusions andproposed contradictory guidelines [1,6,8]. Nevertheless,antimicrobial prophylaxis has become a standard practice inmany institutions. In a UK survey performed in 1997, as manyas 90% of surgeons prescribed it, as did, more recently, 73%of 329 members of the European chapter of the InternationalHepato-Biliary Association [9].Candida has been found in 15% to 70% of infected necrotictissues of patients requiring surgery, and these highproportions have been repeatedly related to prior antibioticexposure, which promotes the overgrowth of unaffected micro-organisms [2,4,7]. In addition, pancreatic fungal infections maybe associated with further increased morbidity and mortality[2,4,5,8].The good safety profile and the excellent bioavailability oftriazole compounds in pancreatic tissues make them goodcandidates for antifungal prophylaxis, but only limited data arePage 2 of 4(page number not for citation purposes)Critical Care    Vol 10 No 5 Eggimann et al.available for their use in severe acute pancreatitis [2,4,10]. Inaddition, the prophylactic trials in surgical patients that havebeen carried out have included only a few patients withpancreatitis. Indirect evidence of potential protection comesfrom trials testing selective digestive decontamination, inwhich lower candidiasis and mortality rates have beenreported [5]. In a unique open randomised study, He andcolleagues [11] investigated the effect of prophylaxis in aseries of 73 severe acute pancreatitis cases. Compared tocontrols, garlicin and fluconazole reduced the rates of fungalinfections from 30% to 16% (p < 0.05) and 9% (p < 0.01),respectively.These data are clearly insufficient to support evidence-basedrecommendations about antifungal prophylaxis in acutepancreatitis. However, according to the preceding argu-ments, I would recommend adding antifungal prophylaxiswith a triazole compound in any patients receivingantibacterial prophylaxis. This prophylaxis may not onlyprevent infection of necrotic pancreatic tissue, but also delaythe need for surgery. As early surgery within the first 2 weekshas been associated with higher mortality rates, this mayhave an impact on the outcome of the patients [1,6].Delayed surgery may allow a more conservative approach,with the use of a minimally invasive procedure, such as extra-abdominal lumbar retroperitoneal debridement on wellcircumscribed collections, for which promising preliminaryresults have been reported [6,7].Con: Prevalence and risks of fungal colonisation of pancreatic necrosisSaurabh Jamdar and Ajith K SiriwardenaFungal colonisation of pancreatic tissue is a feared compli-cation of severe acute pancreatitis. Invasive candidiasis canbe associated with mortality rates in excess of 40% [12] and,once colonised, eradication of fungi from the poorly perfusedperi-pancreatic tissues of the retroperitoneum may bedifficult.The risks of fungal colonisation of pancreatic necrosis arebrought into focus in contemporary critical care practice as aresult of recent trends in antibiotic use and trends in surgicaldebridement of infected necrosis. Several small randomisedtrials of antibiotic prophylaxis in severe acute pancreatitis[13-15] together with a meta-analysis [16] and a Cochranesystematic review [17] have indicated an improvement inoutcome in those patients receiving antibiotics. This evidencehas resulted in antibiotic prophylaxis being recommended inseveral published guidelines for the treatment of severe acutepancreatitis [8,18,19]. Although the Cochrane systematicreview [17] concluded that there was no increasedpreponderance of fungal infection in patients in the treatmentarms compared to placebo, this finding is not necessarily atodds with evidence of increased prevalence of fungalcolonization in critically ill surgical patients and, recently,Isenmann and colleagues [5] demonstrated that prolongedantibiotic therapy was associated with a high incidence ofCandida-infected pancreatic necrosis. The advent ofantibiotic prophylaxis in the management of severe acutepancreatitis has probably also contributed to a significantshift in the profile of pathogenic organisms. The resistant floraencountered following such therapy include multi-resistantGram-positive cocci, Gram-negative bacilli and fungi.To date, no randomised trial has examined the role of anti-fungal prophylaxis in patients with severe acute pancreatitisand practice guidelines must thus be based on extrapolationof current evidence. The Ostrosky-Zeichner clinical predictionrule [20] defines patients with pancreatitis (with central linesand receiving broad spectrum antibiotics) as being at highrisk for fungal colonisation. Incorporation of evidence fromstudies in parallel patient populations is central to theconstruction of a rational policy for severe acute pancreatitisand the recent detailed meta-analysis of fluconazoleprophylaxis in critically ill surgical patients concluded that,although treatment was associated with lower fungalcolonisation rates, there was no evidence of a reduction inmortality [21]. In data specific to acute pancreatitis, He andcolleagues [11] from Hunan, China, demonstrated in a studyof 70 patients that colonisation in individuals receivingfluconazole prophylaxis (n = 22) was 9% compared to 23control patients in whom colonisation rates were 30%. Aretrospective analysis of 46 patients with infected pancreaticnecrosis demonstrated that the early administration ofantifungal therapy (defined as at least 48 hours beforesurgical intervention) reduced subsequent fungal infectionrates but not mortality [22].Synthesising this evidence into a practical managementalgorithm would suggest that there are limited grounds forroutine antifungal prophylaxis in patients with severe acutepancreatitis even if these patients are receiving antibiotictherapy. The subset of patients with on-going diseaserequiring prolonged critical care support, where antibioticprophylaxis has transformed into specific broad-spectrumantimicrobial therapy and, in particular, where trans-abdominalpercutaneous drains are in place (in addition to central venouscatheters), can be regarded as a subset of critically ill patientswith high on-going organ dysfunction scores where antifungalprophylaxis can be considered. Even in this setting, it must beacknowledged that there is little evidence that antifungalprophylaxis is associated with a reduction in mortality and,further, that this intervention may be associated with a higherincidence of resistant candidal species [21].Page 3 of 4(page number not for citation purposes)Available online http://ccforum.com/content/10/5/229Pro’s response: Both antimicrobial and antifungal prophylaxis should be restricted to a limitednumber of critically ill patientsPhilippe EggimannI agree with the outstanding arguments of my opponent.In addition, recent evidence further supports the generalisationof antimicrobial prophylaxis [23]. While waiting for the resultsof eventual large randomised studies, we need to propose asimplified pragmatic approach for the daily care of critically illpatients admitted for necrotizing pancreatitis.Currently, according to the ecological impact of antimicrobialprophylaxis, antifungals should be considered for all patientsreceiving it. However, my second recommendation will be tostrongly restrict both antimicrobial and antifungal prophylaxisto the subset of the most severely ill patients, carefullyselected after extensive diagnostic workup [24].Con’s response: Antifungal prophylaxis does not reduce mortality in severe acute pancreatitisSaurabh Jamdar and Ajith K SiriwardenaDr Eggiman’s key point is that co-prescription of an antifungalat the time of commencement of antibiotic prophylaxis may”delay the need for surgery”. There is now broad consensusthat surgical intervention for pancreatic necrosis should bedeferred, if possible, during the first 21 days. However, thereis no suggestion that antifungal therapy helps to deferintervention. In contrast, routine use of antifungal therapy isnot only over-used but is likely to encourage the emergenceof resistant species in precisely those patients who areeventually most likely to require specific antifungal treatment:patients with severe acute pancreatitis undergoingradiological or surgical intervention.Competing interestsPE has collaborated on several industry-sponsored clinicaltrials since 1990. He has served on an advisory board and/orsponsorized meetings and/or lectures for B-Braun, CookCritical Care, Lilly, Medex, Merck Sharp & Dohme-Chibret,Pfizer, Roche and Wyeth-Lederle.References1. Whitcomb DC: Clinical practice. Acute pancreatitis. N Engl JMed 2006, 354:2142-2150.2. Shanmugam N, Isenmann R, Barkin JS, Beger HG: Pancreaticfungal infection. Pancreas 2003, 27:133-138.3. Beger HG, Rau B, Mayer J, Pralle U: Natural course of acute pan-creatitis. World J Surg 1997, 21:130-135.6. Beattie GC, Mason J, Swan D, Madhavan KK, Siriwardena AK:Outcome of necrosectomy in acute pancreatitis: the case forcontinued vigilance. Scand J Gastroenterol 2002, 37:1449-1453.7. Besselink MG, de Bruijn MT, Rutten JP, Boermeester MA, HofkerHS, Gooszen HG: Surgical intervention in patients with necro-tizing pancreatitis. Br J Surg 2006, 93:593-599.8. Nathens AB, Curtis JR, Beale RJ, Cook DJ, Moreno RP, RomandJA, Skerrett SJ, Stapleton RD, Ware L, Waldmann CS: Manage-ment of the critically ill patient with severe acute pancreatitis.Crit Care Med 2004, 32:2524-2536.9. King NK, Siriwardena AK: European survey of surgical strate-gies for the management of severe acute pancreatitis. Am JGastroenterol 2004, 99:719-728.4. De Waele JJ, Vogelaers D, Blot S, Colardyn F: Fungal infectionsin patients with severe acute pancreatitis and the use of pro-phylactic therapy. Clin Infect Dis 2003, 37:208-213.5. Isenmann R, Schwarz M, Rau B, Trautmann M, Schober W,Beger HG: Characteristics of infection with Candida speciesin patients with necrotizing pancreatitis. World J Surg 2002,26:372-376.10. Shrikhande S, Friess H, Issenegger C, Martignoni ME, Yong H,Gloor B, Yeates R, Kleeff J, Büchler M: Fluconazole penetrationinto the pancreas. Antimicrob Agents Chemother 2000, 44:2569-2571.11. He YM, Lv XS, Ai ZL, Liu ZS, Qian Q, Sun Q, Chen JW, Lei DX,Jiang CQ, Yuan YF: Prevention and therapy of fungal infectionin severe acute pancreatitis: A prospective clinical study.World J Gastroenterol 2003, 9:2619-2621.12. Eggimann P, Francioli P, Bille J, Schneider R, Wu MM, ChapuisG, Chiolero R, Pannatier A, Schilling J, Geroulanos S, et al.: Flu-canozole prophylaxis prevents intra-abdominal candidiasis inhigh-risk surgical patients. Crit Care Med 1999, 27:1066-1072.13. Pederzoli P, Bassi C, Vesentini S, Camedelli A: A randomisedmulticentre clinical trial of antibiotic prophylaxis of septiccomplications in acute pancreatitis with impenem. SurgGynecol Obstet 1993, 176:480-483.14. Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, KivisaariL, Valtonen V, Haapiainen R, Schroder T, Kivilaakso E: Earlyantibiotic treatment in acute necrotising pancreatitis. Lancet1995, 346:663-667.15. Delcenserie R, Yzet T, Ducroix JP: Prophylactic antibiotics intreatment of severe acute pancreatitis. Pancreas 1996, 13:198-201.16. Sharma VK, Howden CW: Prophylactic antibiotic administra-tion reduces sepsis and mortality in acute necrotizing pancre-atitis: a meta-analysis. Pancreas 2001, 22:28-31.17. Bassi C, Larvin M, Villatoro E: Antibiotic therapy for prophylaxisagainst infection of pancreatic necrosis in acute pancreatitis.Cochrane Database Syst Rev 2003, 4:CD002941.18. Working party of the British Society of Gastroenterology; Associ-ation of Surgeons of Great Britain and Ireland; Pancreatic Societyof Great Britain and Ireland; Association of Upper GI Surgeons ofGreat Britain and Ireland: UK guidelines for the managementof acute pancreatitis. Gut 2005, 54(Suppl 3):iii1-9.19. Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG,Carter R, Di Magno E, Banks PA, Whitcomb DC, et al.; Interna-tional Association of Pancreatology: IAP Guidelines for the sur-gical management of acute pancreatitis. Pancreatology 2002,2:565-573.20. Paphitou NI, Ostrosky-Zeichner L, Rex JH: Rules for identifyingpatients at increased risk for candidal infections in the surgi-cal intensive care unit: approach to developing practical crite-ria for systematic use in antifungal prophylaxis trials. MedMycol 2005, 43:235-243.21. Shorr AF, Chung K, Jackson WL, Waterman PE, Kollef MH: Flu-conazole prophylaxis in critically ill surgical patients: a meta-analysis. Crit Care Med 2005, 33:1928-1935.22. King NK, Siriwardana HP, Wood B, Siriwardena AK: Trends infungal colonization of pancreatic necrosis in patients under-going necrosectomy for acute pancreatitis. HPB 2005, 7:120-123.23. Moyshenyat I, Mandell E, Tenner S: Antibiotic prophylaxis ofpancreatic infection in patients with necrotizing pancreatitis:rationale, evidence, and recommendations. Curr GastroenterolRep 2006, 8:121-126.24. Eggimann P, Garbino J, Pittet D: Management of Candidaspecies infections in critically ill patient. Lancet Infect Dis2003, 3:772-785.Critical Care    Vol 10 No 5 Eggimann et al.Page 4 of 4(page number not for citation purposes)

Pro/con debate: antifungal prophylaxis is important to prevent fungal infection in patients with acute necrotizing pancreatitis receiving broad-spectrum antibiotics

UNIL IRIS | Institutional Research Information System

Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev

Camedelli A: A randomised multicentre clinical trial of antibiotic prophylaxis of septic complications in acute pancreatitis with impenem. Surg Gynecol Obstet

Clinical practice. Acute pancreatitis.

Colardyn F: Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Clin Infect Dis

CS: Management of the critically ill patient with severe acute pancreatitis. Crit Care Med

Ducroix JP: Prophylactic antibiotics in treatment of severe acute pancreatitis. Pancreas

Flucanozole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med

Fluconazole penetration into the pancreas. Antimicrob Agents Chemother

HG: Characteristics of infection with Candida species in patients with necrotizing pancreatitis.

HG: Pancreatic fungal infection. Pancreas

Hofker HS, Gooszen HG: Surgical intervention in patients with necrotizing pancreatitis.

Howden CW: Prophylactic antibiotic administration reduces sepsis and mortality in acute necrotizing pancreatitis: a meta-analysis. Pancreas

International Association of Pancreatology: IAP Guidelines for the surgical management of acute pancreatitis. Pancreatology

Kivilaakso E: Early antibiotic treatment in acute necrotising pancreatitis. Lancet

Kollef MH: Fluconazole prophylaxis in critically ill surgical patients: a metaanalysis. Crit Care Med

Management of Candida species infections in critically ill patient. Lancet Infect Dis

S: Antibiotic prophylaxis of pancreatic infection in patients with necrotizing pancreatitis: rationale, evidence, and recommendations. Curr Gastroenterol Rep

Siriwardena AK: European survey of surgical strategies for the management of severe acute pancreatitis.

Siriwardena AK: Outcome of necrosectomy in acute pancreatitis: the case for continued vigilance.

Siriwardena AK: Trends in fungal colonization of pancreatic necrosis in patients undergoing necrosectomy for acute pancreatitis. HPB

U: Natural course of acute pancreatitis.

Working party of the British Society of Gastroenterology; Association of Surgeons of Great Britain and Ireland;

YF: Prevention and therapy of fungal infection in severe acute pancreatitis: A prospective clinical study.

https://serval.unil.ch/resource/serval:BIB_A0DA346CF68F.P001/REF.pdf

Pro/con debate: antifungal prophylaxis is important to prevent fungal infection in patients with acute necrotizing pancreatitis receiving broad-spectrum antibiotics

Abstract

Similar works

Full text

Available Versions

Serveur académique lausannois

UNIL IRIS | Institutional Research Information System