Infectious complications in surgical patients often originate from the intestinal microflora. In the critically ill patient, small bowel motility is disturbed, leading to bacterial overgrowth and subsequent bacterial translocation due to dysfunction of the gut mucosal barrier. The optimal prophylactic strategy should act on all these factors, but such a strategy is not yet available. For several decades, antibiotic prophylaxis to prevent translocation of pathogenic bacteria has been studied with conflicting results. Selective decontamination of the digestive tract has shown good results, but fear for bacterial multiresistance has prevented worldwide implementation. In recent years, probiotics, living bacteria with a potential beneficial effect to their host, have shown promising results in several randomized placebo-controlled trials. Currently, in vitro and experimental research focuses on the effects of probiotics on the microflora responsible for gut-derived infections, structural mucosal barrier function and the immune system.

1.
Bonten MJ, Mascini EM: The hidden faces of the epidemiology of antibiotic resistance. Intensive Care Med 2003;29:1–2.
2.
Levy J: The effects of antibiotic use on gastrointestinal function. Am J Gastroenterol 2000;95:S8–S10.
3.
Imahara SD, Nathens AB: Antimicrobial strategies in surgical critical care. Curr Opin Crit Care 2003;9:286–291.
4.
Vriens M, Blok H, Fluit A, Troelstra A, Van Der WC, Verhoef J: Costs associated with a strict policy to eradicate methicillin-resistant Staphylococcus aureus in a Dutch University Medical Center: a 10-year survey. Eur J Clin Microbiol Infect Dis 2002;21:782–786.
5.
Clark NM, Patterson J, Lynch JP III: Antimicrobial resistance among gram-negative organisms in the intensive care unit. Curr Opin Crit Care 2003;9:413–423.
6.
Sorberg M, Farra A, Ransjo U, Gardlund B, Rylander M, Settergren B, Kalin M, Kronvall G: Different trends in antibiotic resistance rates at a university teaching hospital. Clin Microbiol Infect 2003;9:388–396.
7.
Murray BE: Vancomycin-resistant enterococcal infections. N Engl J Med 2000;342:710–721.
8.
Leavis HL, Willems RJ, Mascini EM, Vandenbroucke-Grauls CM, Bonten MJ: Vancomycin-resistant enterococci in the Netherlands (in Dutch). Ned Tijdschr Geneeskd 2004;148:878–882.
9.
Albrich WC, Angstwurm M, Bader L, Gartner R: Drug resistance in intensive care units. Infection 1999;27(suppl 2):S19–S23.
10.
Berrouane YF, Herwaldt LA, Pfaller MA: Trends in antifungal use and epidemiology of nosocomial yeast infections in a university hospital. J Clin Microbiol 1999;37:531–537.
11.
Deitch EA: The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure. Arch Surg 1990;125:403–404.
12.
Deitch EA: Bacterial translocation: the influence of dietary variables. Gut 1994;35:S23–S27.
13.
Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH, Wolff M, Spencer RC, Hemmer M: The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA 1995;274:639–644.
14.
Van Saene HK, Petros AJ, Ramsay G, Baxby D: All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth. Intensive Care Med 2003;29:677–690.
15.
De Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, Kesecioglu J: Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003;362:1011–1016.
16.
Namias N, Harvill S, Ball S, McKenney MG, Salomone JP, Civetta JM: Cost and morbidity associated with antibiotic prophylaxis in the ICU. J Am Coll Surg 1999;188:225–230.
17.
Van Nieuwenhoven CA, Buskens E, Van Tiel FH, Bonten MJ: Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients. JAMA 2001;286:335–340.
18.
Beger HG, Rau B, Isenmann R, Schwarz M, Gansauge F, Poch B: Antibiotic prophylaxis in severe acute pancreatitis. Pancreatology 2005;5:10–19.
19.
Isenmann R, Runzi M, Kron M, Kahl S, Kraus D, Jung N, Maier L, Malfertheiner P, Goebell H, Beger HG: Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial. Gastroenterology 2004;126:997–1004.
20.
Tenover FC, Hughes JM: WHO Scientific Working Group on monitoring and management of bacterial resistance to antimicrobial agents. Emerg Infect Dis 1995;1:37.
21.
Besselink MG, Bollen TL, Boermeester MA, Van Ramshorst B, Van Leeuwen MS, Gooszen HG: Timing and choice of intervention in necrotising pancreatitis (in Dutch). Ned Tijdschr Geneeskd 2005;149:501–506.
22.
Besselink MG, Van Minnen LP, Van Erpecum KJ, Bosscha K, Gooszen HG: Beneficial effects of ERCP and papillotomy in predicted severe biliary pancreatitis. Hepatogastroenterology 2005;52:37–39.
23.
Besselink MGH, Nieuwenhuijs VB, De Bruijn MT, Van Minnen LP, Gooszen HG: Prophylactic use of antibiotics in acute (necrotizing) pancreatitis: results of a new meta-analysis. Eur J Gastroenterol Hepatol 2003;15:A1–76.
24.
Besselink MGH, De Bruijn MT, Rutten JP, Hofker HS, Boermeester MA, Van Ramshorst B, Schaapherder AF, Dejong CH, Van Eijck CJH, Pierie JPEN, Van Goor H, Cuesta MA, Lange JF, Gooszen HG: Surgical intervention for acute necrotizing pancreatitis in the Netherlands. Dutch Acute Pancreatitis Study Group 2000–2003. Submitted for publication.
25.
Besselink MGH, Timmerman HM, Buskens E, Nieuwenhuijs VB, Akkermans LMA, Gooszen HG: Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a blinded, placebo-controlled randomised controlled trial. Dutch Acute Pancreatitis Study Group. BMC Surg 2004 Sep 29;4:12.
26.
Bosscha K, Hulstaert PF, Hennipman A, Visser MR, Gooszen HG, Van Vroonhoven TJ, Werken C: Fulminant acute pancreatitis and infected necrosis: results of open management of the abdomen and ‘planned’ reoperations. J Am Coll Surg 1998;187:255–262.
27.
Bosscha K, Nieuwenhuijs VB, Vos A, Samsom M, Roelofs JM, Akkermans LM: Gastrointestinal motility and gastric tube feeding in mechanically ventilated patients. Crit Care Med 1998;26:1510–1517.
28.
Bosscha K, Reijnders K, Jacobs MH, Post MWM, Algra A, Van der Werken C: Quality of life after severe bacterial peritonitis and infected necrotizing pancreatitis treated with open management of the abdomen and planned re-operations. Crit Care Med 2001;29:1539–1543.
29.
Niers LEM, Rijkers GT, Timmerman HM, Van Bleek GM, Van Uden NOP, Kimpen JLL, Hoekstra MO: A central immunoregulatory role for IL-10 in the suppression of type 2 T-helper cell cytokines by probiotic bacteria. XXIII EAACI Congress, Amsterdam 2004.
30.
Nieuwenhuijs VB, Verheem A, Duijvenbode-Beumer H, Visser MR, Verhoef J, Gooszen HG, Akkermans LM: The role of interdigestive small bowel motility in the regulation of gut microflora, bacterial overgrowth, and bacterial translocation in rats. Ann Surg 1998;228:188–193.
31.
Nieuwenhuijs VB, Duijvenbode-Beumer H, Verheem A, Visser MR, Verhoef J, Gooszen HG, Akkermans LM: The effects of ABT-229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats. Eur J Clin Invest 1999;29:33–40.
32.
Nieuwenhuijs VB, Van Dijk JE, Gooszen HG, Akkermans LM: Obstructive jaundice, bacterial translocation and interdigestive small-bowel motility in rats. Digestion 2000;62:255–261.
33.
Nieuwenhuijs VB, Besselink MG, Van Minnen LP, Gooszen HG: Surgical management of acute necrotizing pancreatitis: a 13-year experience and a systematic review. Scand J Gastroenterol Suppl 2003;239:111–116.
34.
Ridwan BU, Besselink MGH, Koning CJM, Gooszen HG, Akkermans LMA: Prevention of secondary pancreatic infections with probiotics; in vitro studies. Submitted for publication.
35.
Timmerman HM, Koning CJM, Mulder L, Rombouts FM, Beynen AC: Monostrain, multistrain and multispecies probiotics. A comparison of functionality and efficacy. Int J Food Microbiol 2004;96:219–233.
36.
Van Felius ID, Akkermans LM, Bosscha K, Verheem A, Harmsen W, Visser MR, Gooszen HG: Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis. Neurogastroenterol Motil 2003;15:267–276.
37.
Van Felius ID, Hendrikse CA, Harmsen W, Visser MR, Smout AJ, Akkermans LM: Induction of small bowel bacterial overgrowth leads to changes in interdigestive motility in healthy volunteers. Utrecht, Utrecht University Thesis 2003;101–115.
38.
Van Minnen LP, Besselink MG, Bosscha K, Van Leeuwen MS, Schipper ME, Gooszen HG: Colonic involvement in acute pancreatitis. A retrospective study of 16 patients. Dig Surg 2004;21:33–40.
39.
Van Felius ID, Kroese ABA, Groot JA, Verheem A, Harmsen W, Visser MR, Gooszen HG, Akkermans LM: Increased small intestinal permeability is correlated to experimental acute pancreatitis. Utrecht, Utrecht University Thesis 2003;85–99.
40.
Van Minnen LP, Nieuwenhuijs VB, De Bruijn MTh, Visser MR, Akkermans LMA, Gooszen HG: Subtotal Colectomy Does Not Reduce Pancreatic Infection in Experimental Acute Pancreatitis. Gastroenterology 2004;126:S2. Abstract.
41.
Bengmark S: Use of some pre-, pro- and synbiotics in critically ill patients. Best Pract Res Clin Gastroenterol 2003;17:833–848.
42.
Hooper LV, Gordon JI: Commensal host-bacterial relationships in the gut. Science 2001;292:1115–1118.
43.
Guarner F, Malagelada JR: Gut flora in health and disease. Lancet 2003;361:512–519.
44.
Bongaerts GP, Severijnen RS: The beneficial, antimicrobial effect of probiotics. Med Hypotheses 2001;56:174–177.
45.
Bengmark S: Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut 1998;42:2–7.
46.
Simon GL, Gorbach SL: Intestinal flora in health and disease. Gastroenterology 1984;86:174–193.
47.
Van der Waaij D, Berghuis-de Vries JM, Lekkerkerk V: Colonization resistance of the digestive tract and the spread of bacteria to the lymphatic organs in mice. J Hyg (Lond) 1972;70:335–342.
48.
Berg RD, Garlington AW: Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun 1979;23:403–411.
49.
Foitzik T, Stufler M, Hotz HG, Klinnert J, Wagner J, Warshaw AL, Schulzke JD, Fromm M, Buhr HJ: Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis. J Gastrointest Surg 1997;1:40–47.
50.
Hotz HG, Foitzik T, Rohweder J, Schulzke JD, Fromm M, Runkel NS, Buhr HJ: Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications. J Gastrointest Surg 1998;2:518–525.
51.
Lange JF, Van Gool J, Tytgat GN: The protective effect of a reduction in intestinal flora on mortality of acute haemorrhagic pancreatitis in the rat. Hepatogastroenterology 1987;34:28–30.
52.
Gordon JI, Hooper LV, McNevin MS, Wong M, Bry L: Epithelial cell growth and differentiation. III. Promoting diversity in the intestine: conversations between the microflora, epithelium, and diffuse GALT. Am J Physiol 1997;273:G565–G570.
53.
Ammori BJ, Leeder PC, King RF, Barclay GR, Martin IG, Larvin M, McMahon MJ: Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality. J Gastrointest Surg 1999;3:252–262.
54.
Rahman SH, Ammori BJ, Holmfield J, Larvin M, McMahon MJ: Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J Gastrointest Surg 2003;7:26–35.
55.
Nagler-Anderson C: Man the barrier! Strategic defences in the intestinal mucosa. Nat Rev Immunol 2001;1:59–67.
56.
Medzhitov R, Preston-Hurlburt P, Janeway CA Jr: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997;388:394–397.
57.
Mowat AM, Thomas MJ, MacKenzie S, Parrott DM: Divergent effects of bacterial lipopolysaccharide on immunity to orally administered protein and particulate antigens in mice. Immunology 1986;58:677–683.
58.
Kraehenbuhl JP, Corbett M: Immunology. Keeping the gut microflora at bay. Science 2004;303:1624–1625.
59.
Rescigno M, Rotta G, Valzasina B, Ricciardi-Castagnoli P: Dendritic cells shuttle microbes across gut epithelial monolayers. Immunobiology 2001;204:572–581.
60.
Macpherson AJ, Uhr T: Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 2004;303:1662–1665.
61.
Freitas M, Tavan E, Cayuela C, Diop L, Sapin C, Trugnan G: Host-pathogens cross-talk. Indigenous bacteria and probiotics also play the game. Biol Cell 2003;95:503–506.
62.
Sansonetti PJ: War and peace at mucosal surfaces. Nat Rev Immunol 2004;4:953–964.
63.
Beger HG, Rau B, Mayer J, Pralle U: Natural course of acute pancreatitis. World J Surg 1997;21:130–135.
64.
Bentrem DJ, Joehl RJ: Pancreas: healing response in critical illness. Crit Care Med 2003;31:S582–S589.
65.
Widdison AL, Karanjia ND: Pancreatic infection complicating acute pancreatitis. Br J Surg 1993;80:148–154.
66.
Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC: Postinjury multiple organ failure: A bimodal phenomenon. J Trauma 1996;40:501–510.
67.
Delcenserie R, Yzet T, Ducroix JP: Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas 1996;13:198–201.
68.
Pederzoli P, Bassi C, Vesentini S: A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 1993;176:480–483.
69.
Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, Kivisaari L, Valtonen V, Haapiainen R, Schroder T, Kivilaakso E: Early antibiotic treatment in acute necrotising pancreatitis. Lancet 1995;346:663–667.
70.
Schwarz M, Isenmann R, Meyer H, Beger HG: Antibiotic use in necrotizing pancreatitis. Results of a controlled study (in German). Dtsch Med Wochenschr 1997;122:356–361.
71.
Stoutenbeek CP, Van Saene HK, Miranda DR, Zandstra DF: The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients. Intensive Care Med 1984;10:185–192.
72.
Luiten EJ, Hop WC, Lange JF, Bruining HA: Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann Surg 1995;222:57–65.
73.
Liberati A, D’Amico R, Pifferi S, Torri V, Brazzi L: Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev 2004;CD000022.
74.
Van Enckevort PJ, Zwaveling JH, Bottema JT, Maring JK, Klompmaker IJ, Slooff MJ, TenVergert EM: Cost effectiveness of selective decontamination of the digestive tract in liver transplant patients. Pharmacoeconomics 2001;19:523–530.
75.
Webb CH: Selective decontamination of the digestive tract, SDD: a commentary. J Hosp Infect 2000;46:106–109.
76.
Guarner F, Schaafsma GJ: Probiotics. Int J Food Microbiol 1998;39:237–238.
77.
Bongaerts GP, Severijnen RS: New strategies in antimicrobial therapy. Med Hypotheses 2001;56:178–180.
78.
Hart AL, Lammers K, Brigidi P, Vitali B, Rizzello F, Gionchetti P, Campieri M, Kamm MA, Knight SC, Stagg AJ: Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 2004;53:1602–1609.
79.
Olah A, Belagyi T, Issekutz A, Gamal ME, Bengmark S: Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis. Br J Surg 2002;89:1103–1107.
80.
Weale R, Edwards A: Letter 1: Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis (Br J Surg 2002;89:1103–1107). Br J Surg 2003;90:122–123.
81.
Rahman SH, Catton JA, McMahon MJ: Letter 2: Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis (Br J Surg 2002;89:1103–1107). Br J Surg 2003;90:122–123.
82.
Rayes N, Seehofer D, Hansen S, Boucsein K, Muller AR, Serke S, Bengmark S, Neuhaus P: Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: A controlled trial in liver transplant recipients. Transplantation 2002;74:123–127.
83.
Rayes N, Seehofer D, Theruvath T, Schiller RA, Langrehr JM, Jonas S, Bengmark S, Neuhaus P: Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation: a randomized, double-blind trial. Am J Transplant 2005;5:125–130.
84.
Anderson AD, McNaught CE, Jain PK, Macfie J: Randomised clinical trial of synbiotic therapy in elective surgical patients. Gut 2004;53:241–245.
85.
Jain PK, McNaught CE, Anderson AD, Macfie J, Mitchell CJ: Influence of synbiotic containing Lactobacillus acidophilus La5, Bifidobacterium lactis Bb 12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose on gut barrier function and sepsis in critically ill patients: a randomised controlled trial. Clin Nutr 2004;23:467–475.
86.
McNaught CE, Woodcock NP, Macfie J, Mitchell CJ: A prospective randomised study of the probiotic Lactobacillus plantarum 299V on indices of gut barrier function in elective surgical patients. Gut 2002;51:827–831.
87.
McNaught CE, Woodcock NP, Anderson AD, Macfie J: A prospective randomised trial of probiotics in critically ill patients. Clin Nutr 2005;24:211–219.
88.
Rayes N, Hansen S, Seehofer D, Muller AR, Serke S, Bengmark S, Neuhaus P: Early enteral supply of fiber and lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery. Nutrition 2002;18:609–615.
89.
Bengmark S: Synbiotics to strengthen gut barrier function and reduce morbidity in critically ill patients. Clin Nutr 2004;23:441–445.
90.
Büchler MW, Gloor B, Muller CA, Friess H, Seiler CA, Uhl W: Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann Surg 2000;232:619–626.
91.
Johnson CD, Abu-Hilal M: Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut 2004;53:1340–1344.
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