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Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Research

Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis

Authors: William Manzanares, Margot Lemieux, Pascal L. Langlois, Paul E. Wischmeyer

Published in: Critical Care | Issue 1/2016

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Abstract

Background

Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness.

Methods

Computerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes.

Results

Thirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I 2 = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I 2 = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists.

Conclusion

Probiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.
Literature
1.
Alverdy JC, Chang FB. The reemerging role of the intestinal flora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away. J Leukoc Biol. 2008;83:461–6.CrossRefPubMed
2.
3.
Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003;167:695–701.CrossRefPubMed
4.
Milbrandt EB, Kersten A, Rahim MT, Dremsizov TT, Clermont G, Cooper LM, Angus DC, Linde-Zwirble WT. Growth of intensive care unit resource use and its estimated cost in Medicare. Crit Care Med. 2008;36:2504–10.CrossRefPubMed
5.
6.
Luyer MD, Buurman WA, Hadfoune M, Speelmans G, Knol J, Jacobs JA, Dejong CH, Vriesema AJ, Greve JW. Strain-specific effects of probiotics on gut barrier integrity following hemorrhagic shock. Infect Immun. 2005;73:3686–92.CrossRefPubMedPubMedCentral
7.
Tok D, Ilkgul O, Bengmark S, Aydede H, Erhan Y, Taneli F, Ulman C, Vatansever S, Kose C, Ok G. Pretreatment with pro- and synbiotics reduces peritonitis-induced acute lung injury in rats. J Trauma. 2007;62:880–5.CrossRefPubMed
8.
Corr SC, Li Y, Riedel CU, O'Toole PW, Hill C, Gahan CG. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci U S A. 2007;104:7617–21.CrossRefPubMedPubMedCentral
9.
Mittal R, Coopersmith CM. Redefining the gut as the motor of critical illness. Trends Mol Med. 2014;20(4):214–23.CrossRefPubMed
10.
Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med. 2010;182:1058–64.CrossRefPubMedPubMedCentral
11.
Hranjec T, Sawyer RG. Management of infections in critically ill patients. Surg Infect. 2014;15:474–8.CrossRef
12.
Siempos II, Ntaidou TK, Falagas ME. Impact of the administration of probiotics on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Crit Care Med. 2010;38:954–62.CrossRefPubMed
13.
Barraud D, Bollaert PE, Gibot S. Impact of the administration of probiotics on mortality in critically ill adult patients. Chest. 2013;143:646–55.CrossRefPubMed
14.
Petrof E, Dhaliwal R, Manzanares W, Johnstone J, Cook D, Heyland DK. Probiotics in the critically ill: a systematic review of the randomized trial evidence. Crit Care Med. 2012;40:3290–302.CrossRefPubMed
15.
Wang J, Liu KX, Ariani F, Tao LL, Zhang J, Qu JM. Probiotics for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of high-quality randomized controlled trials. PLoS One. 2013;8, e83934.CrossRefPubMedPubMedCentral
16.
Gu WJ, Wei CY, Yin RX. Lack of efficacy of probiotics in preventing ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. Chest. 2012;142:859–68.CrossRefPubMed
17.
Bo L, Li J, Tao T, Bai Y, Ye X, Hotchkiss RS, Kollef MH, Crooks NH, Deng X. Probiotics for preventing ventilator-associated pneumonia. Cochrane Database Syst Rev. 2014;(10)CD009066.
18.
McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C, Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016;40:159–211.CrossRefPubMed
19.
20.
Cui LH, Wang XH, Peng LH, Yu L, Yang YS. The effects of early enteral nutrition with addition of probiotics on the prognosis of patients suffering from severe acute pancreatitis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2013;25:224–8.PubMed
21.
Tan M, Lu X, Duan JW, Peng H, Zhu JC. Effects of probiotics on blood glucose levels and clinical outcomes in patients with severe cranocerebral trauma. Chin Crit Care Med. 2013;25:627–30.
22.
Wang G, Wen J, Xu L, Zhou S, Gong M, Wen P, Xiao X. Effect of enteral nutrition and ecoimmunonutrition on bacterial translocation and cytokine production in patients with severe acute pancreatitis. J Surg Res. 2013;183:592–7.CrossRefPubMed
23.
López de Toro Martín-Consuegra I, Sanchez-Casado M, Pérez-Pedrero Sánchez-Belmonte MJ, López-Reina Torrijos P, Sánchez-Rodriguez P, Raigal-Caño A, Heredero-Galvez E, Zubigaray SB, Arrese-Cosculluela MÁ. The influence of symbiotics in multi-organ failure: randomised trial. Med Clin (Barc). 2014;143:143–9.CrossRef
24.
Sanaie S, Ebrahimi-Mameghani M, Hamishehkar H, Mojtahedzadeh M, Mahmoodpoor A. Effect of a multispecies probiotic on inflammatory markers in critically ill patients: A randomized, double-blind, placebo-controlled trial. J Res Med Sci. 2014;19:827–33.PubMedPubMedCentral
25.
Rongrungruang Y, Krajangwittaya D, Pholtawornkulchai K, Tiengrim S, Thamlikitkul V. Randomized controlled study of probiotics containing Lactobacillus casei (Shirota strain) for prevention of ventilator-associated pneumonia. J Med Assoc Thai. 2015;98:253–159.
26.
Zeng J, Wang CT, Zhang FS, Qi F, Wang SF, Ma S, Wu TJ, Tian H, Tian ZT, Zhang SL, Qu Y, Liu LY, Li YZ, Cui S, Zhao HL, Du QS, Ma Z, Li CH, Li Y, Si M, Chu YF, Meng M, Ren HS, Zhang JC, Jiang JJ, Ding M, Wang YP. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intensive Care Med. 2016. Epub ahead of print.
27.
Wheeler KE, Cook DJ, Mehta S, Calce A, Guenette M, Perreault MM, Thiboutot Z, Duffett M, Burry L. Use of probiotics to prevent ventilator-associated pneumonia: A survey of pharmacists' attitudes. J Crit Care. 2016;31:221–6.CrossRefPubMed
28.
29.
30.
Tempe JD, Steidel AL, Blehaut H, Hasselmann M, Lutun P, Maurier F. Prevention of diarrhea administering Saccharomyces boulardii during continuous enteral feeding. Sem Hosp. 1983;59:1409–12.
31.
Schlotterer M, Bernasconi P, Lebreton F, Wasserman D. Intérêt de Saccharomyces boulardii dans la tolérance digestive de la nutrition entérale à debit continu chez le brulé. Nutr Clin Métabol. 1987;1:31–4.CrossRef
32.
Heimburger DC, Sockwell DG, Geels WJ. Diarrhea with enteral feeding: prospective reappraisal of putative causes. Nutrition. 1994;10:392.PubMed
33.
Bleichner G, Blehaut H, Mentec H, Moyse D. Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. A multicenter, randomized, double-blind placebo-controlled trial. Intensive Care Med. 1997;23:517–23.CrossRefPubMed
34.
Kecskés G, Belágyi T, Oláh A. Early jejunal nutrition with combined pre- and probiotics in acute pancreatitis--prospective, randomized, double-blind investigations [Article in Hungarian]. Magy Seb. 2003;56:3–8.PubMed
35.
Lu X, Han CM, Yu JX, Fu SZ. Preliminary comparative study on the effects of early enteral supplementation of synbiotics on severely burned patients. [Article in Chinese]. Zhonghua Shao Shang Za Zhi. 2004;20:198–201.PubMed
36.
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;23:467–75.CrossRefPubMed
37.
Klarin B, Johansson ML, Molin G, Larsson A, Jeppsson B. Adhesion of the probiotic bacterium Lactobacillus plantarum 299v onto the gut mucosa in critically ill patients: a randomised open trial. Crit Care. 2005;9:R285–293.CrossRefPubMedPubMedCentral
38.
McNaught CE, Woodcock NP, Anderson AD, MacFie J. A prospective randomised trial of probiotics in critically ill patients. Clin Nutr. 2005;24:211–9.CrossRefPubMed
39.
Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a symbiotic formula (Synbiotic 2000Forte) in critically ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006;30:1848–55.CrossRefPubMed
40.
Alberda C, Gramlich L, Meddings J, Field C, McCargar L, Kutsogiannis D, Fedorak R, Madsen K. Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2007;85:816–23.PubMed
41.
Li YM. Adjuvant therapy for probiotics in patients with severe acute pancreatitis: an analysis of 14 cases. World Chin J Digestol. 2007;15:302–4.
42.
Olah A, Belagyi T, Poto L, Romics Jr L, Bengmark S. Synbiotic control of inflammation and infection in severe acute pancreatitis: a prospective, randomized, double blind study. Hepatogastroenterolgy. 2007;54:590–4.
43.
Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG, Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:651–9.CrossRefPubMed
44.
Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C. Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care. 2008;12:R69.CrossRefPubMedPubMedCentral
45.
Klarin B, Wullt M, Palmquist I, Molin G, Larsson A, Jeppsson B. Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics. Acta Anaesthesiol Scand. 2008;52:1096–102.CrossRefPubMed
46.
Knight DJ, Gardiner D, Banks A, Snape SE, Weston VC, Bengmark S, Girling KJ. Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial. Intensive Care Med. 2009;35:854–61.CrossRefPubMed
47.
Barraud D, Blard C, Hein F, Marçon O, Cravoisy A, Nace L, Alla F, Bollaert PE, Gibot S. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care Med. 2010;36:1540–7.CrossRefPubMed
48.
Frohmader TJ, Chaboyer WP, Robertson IK, Gowardman J. Decrease in frequency of liquid stool in enterally fed critically ill patients given the multispecies probiotic VSL#3: a pilot trial. Am J Crit Care. 2010;19:e1–11.CrossRefPubMed
49.
Ferrie S, Daley M. Lactobacillus GG as treatment for diarrhea during enteral feeding in critical illness: randomized controlled trial. JPEN J Parenter Enteral Nutr. 2011;35:43–9.CrossRefPubMed
50.
Sharma B, Srivastava S, Singh N, Sachdev V, Kapur S, Saraya A. Role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis: a double-blind randomized controlled trial. J Clin Gastroenterol. 2011;45:442–8.CrossRefPubMed
51.
Tan M, Zhu JC, Du J, Zhang LM, Yin HH. Effects of probiotics on serum levels of Th1/Th2 cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study. Crit Care. 2011;15:R290.CrossRefPubMedPubMedCentral
52.
Morrow LE, Gogineni V, Malesker MA. Synbiotics and probiotics in the critically ill after the PROPATRIA trial. Curr Opin Clin Nutr Metab Care. 2012;15:147–50.CrossRefPubMed
53.
Sheldon T. Dutch probiotics study is criticised for its "design, approval, and conduct". BMJ. 2010;340:c77.CrossRefPubMed
54.
Gou S, Yang Z, Liu T, Wu H, Wang C. Use of probiotics in the treatment of severe acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials. Crit Care. 2014;18:R57.CrossRefPubMedPubMedCentral
55.
Hempel S, Newberry S, Ruelaz A, Wang Z, Miles JNV, Suttorp MJ, Johnsen B, Shanman R, Slusser W, Fu N, Smith A, Roth E, Polak J, Motala A, Perry T, Shekelle PG. Safety of Probiotics to Reduce Risk and Prevent or Treat Disease. Evidence Report/Technology Assessment No. 200. (Prepared by the Southern California Evidence-based Practice Center under Contract No. 290-2007-10062-I.) AHRQ Publication No. 11-E007. April 2011. Available at: www.​ahrq.​gov/​clinic/​tp/​probiotictp.​htm. Accessed 15 June 2016.
56.
De Groote MA, Frank DN, Dowell E, Glode MP, Pace NR. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J. 2005;24:278–80.CrossRefPubMed
57.
Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.CrossRefPubMed
58.
Ego A, Preiser JC, Vincent JL. Impact of diagnostic criteria on the incidence of ventilator-associated pneumonia. Chest. 2015;147:347–55.CrossRefPubMed
59.
Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture positive pneumonia. Chest. 2005;128:3854–62.CrossRefPubMed
60.
Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH, VAP Outcomes Scientific Advisory Group. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest. 2002;122:2115–21.CrossRefPubMed
61.
Branch-Elliman W, Wright SB, Howell MD. Determining the ideal strategy for ventilator-associated pneumonia. Am J Respir Crit Care Med. 2015;192:57–63.CrossRefPubMed
62.
Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B, Shekelle PG. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307:1959–69.CrossRefPubMed
63.
Goldenberg JZ, Ma SS, Saxton JD, Martzen MR, Vandvik PO, Thorlund K, Guyatt GH, Johnston BC. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2013;5, CD006095.
64.
Glenting J, Beck HC, Vrang A, Riemann H, Ravn P, Hansen AM, Antonsson M, Ahrné S, Israelsen H, Madsen S. Anchorless surface associated glycolytic enzymes from Lactobacillus plantarum299v bind to epithelial cells and extracellular matrix proteins. Microbiol Res. 2013;168:245–53.CrossRefPubMed
65.
Gross G, Snel J, Boekhorst J, Smits MA, Kleerebezem M. Biodiversity of mannose-specific adhesion in Lactobacillus plantarum revisited: strain-specific domain composition of the mannose-adhesin. Benef Microbes. 2010;1:61–6.CrossRefPubMed
66.
Metadata
Title
Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis
Authors
William Manzanares
Margot Lemieux
Pascal L. Langlois
Paul E. Wischmeyer
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1434-y

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