Intensive Care Medicine

, Volume 42, Issue 6, pp 1018–1028 | Cite as

Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial

  • Juan Zeng
  • Chun-Ting Wang
  • Fu-Shen Zhang
  • Feng Qi
  • Shi-Fu Wang
  • Shuang Ma
  • Tie-Jun Wu
  • Hui Tian
  • Zhao-Tao Tian
  • Shu-Liu Zhang
  • Yan Qu
  • Lu-Yi Liu
  • Yuan-Zhong Li
  • Song Cui
  • He-Ling Zhao
  • Quan-Sheng Du
  • Zhuang Ma
  • Chun-Hua Li
  • Yun Li
  • Min Si
  • Yu-Feng Chu
  • Mei Meng
  • Hong-Sheng Ren
  • Ji-Cheng Zhang
  • Jin-Jiao Jiang
  • Min Ding
  • Yu-Ping Wang
Original

Abstract

Purpose

To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP).

Methods

This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter.

Results

The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay.

Conclusion

Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.

Keywords

Probiotics Ventilator-associated pneumonia Prevention and control Gastric colonization 

Notes

Acknowledgments

We thank Man Chen, Xin Qu, and Guo-qiang Qie from the Intensive Care Unit, Shandong Provincial Hospital affiliated to Shandong University, People’s Republic of China for advice and copy-editing. This clinical trial was funded by grants from the Specific Fund of Clinical Medical Research of the Chinese Medical Association (No: 10030180240) and from the National Natural Science Foundation of China (No: 81200238).

Compliance with ethical standards

Conflicts of interest

All authors declare that they have no conflict of interest regarding the submission and publication of the work reported here.

Supplementary material

134_2016_4303_MOESM1_ESM.doc (42 kb)
Supplementary material 1 (DOC 42 kb)

References

  1. 1.
    Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R et al (2002) Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 122:2115–2121. doi: 10.1378/chest.122.6.2115 CrossRefPubMedGoogle Scholar
  2. 2.
    Safdar N, Dezfulian C, Collard HR, Saint S (2005) Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 33:2184–2193. doi: 10.1097/01.CCM.0000181731.53912.D9 CrossRefPubMedGoogle Scholar
  3. 3.
    de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS et al (2009) Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 360:20–31. doi: 10.1056/NEJMoa0800394 CrossRefPubMedGoogle Scholar
  4. 4.
    de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J et al (2003) Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 362:1011–1016. doi: 10.1016/S0140-6736(03)14409-1 CrossRefPubMedGoogle Scholar
  5. 5.
    Lingnau W, Berger J, Javorsky F, Fille M, Allerberger F, Benzer H (1998) Changing bacterial ecology during a five-year period of selective intestinal decontamination. J Hosp Infect 39:195–206. doi: 10.1016/S0195-6701(98)90258-4 CrossRefPubMedGoogle Scholar
  6. 6.
    Ebner W, Kropec-Hübner A, Daschner FD (2000) Bacterial resistance and overgrowth due to selective decontamination of the digestive tract. Eur J Clin Microbiol Infect Dis 19:243–247. doi: 10.1007/s100960050470 CrossRefPubMedGoogle Scholar
  7. 7.
    Lilly DM, Stillwell RH (1965) Probiotics: growth promoting factors produced by microorganisms. Science 147:747–748. doi: 10.1126/science.147.3659.747 CrossRefPubMedGoogle Scholar
  8. 8.
    Zeng J, Li YQ, Zuo XL, Zhen YB, Yang J, Liu CH (2008) Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 28:994–1002. doi: 10.1111/j.1365-2036.2008.03818.x CrossRefPubMedGoogle Scholar
  9. 9.
    Gill HS, Guarner F (2004) Probiotics and human health: a clinical perspective. Postgrad Med J 80:516–526. doi: 10.1136/pgmj.2003.008664 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Jacobi CA, Schulz C, Malfertheiner P (2011) Treating critically ill patients with probiotics: beneficial or dangerous? Gut Pathogens 3:2. doi: 10.1186/1757-4749-3-2 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Klarin B, Molin G, Jeppsson B, Larsson A (2008) Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Crit Care 12:R136. doi: 10.1186/cc7109 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Manley KJ, Fraenkel MB, Mayall BC, Power DA (2007) Probiotic treatment of vancomycin-resistant enterococci: a randomised controlled trial. Med J Aust 186:454–457PubMedGoogle Scholar
  13. 13.
    Schultz MJ, Juffermans NP (2010) Prevention of VAP: “WHAP” should we do? Crit Care Med 38:706–707. doi: 10.1097/CCM.0b013e3181bfea4b CrossRefPubMedGoogle Scholar
  14. 14.
    Chinese Society of Critical Care Medicine (2013) The guidelines for prevention, diagnosis and treatment of ventilator-associated pneumonia (2013). Zhonghua Nei Ke Za Zhi 52:524–543. doi: 10.3760/cma.j.issn.0578-1426.2013.06.024 Google Scholar
  15. 15.
    Morrow LE, Kollef MH, Casale TB (2010) Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med 182:1058–1064. doi: 10.1164/rccm.200912-1853OC CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bergmans DCJJ, Bonten MJM, Gaillard CA, Paling JC, van der Geest S, van Tiel FH et al (2001) Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med 164:382–388. doi: 10.1164/ajrccm.164.3.2005003 CrossRefPubMedGoogle Scholar
  17. 17.
    Giamarellos-Bourboulis EJ, Bengmark S, Kanellakopoulou K, Kotzampassi K (2009) Pro- and synbiotics to control inflammation and infection in patients with multiple injuries. J Trauma 67:815–821. doi: 10.1097/TA.0b013e31819d979e CrossRefPubMedGoogle Scholar
  18. 18.
    Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E (2006) Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically ill trauma patients: early results of a randomized controlled trial. World J Surg 30:1848–18455. doi: 10.1007/s00268-005-0653-1 CrossRefPubMedGoogle Scholar
  19. 19.
    Spindler-Vesel A, Benkgmark S, Vovk I, Cerovic O, Kompan L (2007) Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. J Parenter Enteral Nutr 31:119–126. doi: 10.1177/0148607107031002119 CrossRefGoogle Scholar
  20. 20.
    Banupriya B, Biswal N, Srinivasaraghavan R, Narayanan P, Mandal J (2015) Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial. Intensive Care Med 41:677–685. doi: 10.1007/s00134-015-3694-4 CrossRefPubMedGoogle Scholar
  21. 21.
    Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C (2008) Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo controlled pilot study in intensive care unit patients. Crit Care 12:R69. doi: 10.1186/cc6907 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Knight DJ, Gardiner D, Banks A, Snape SE, Weston VC, Bengmark S et al (2009) 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 35:854–861. doi: 10.1007/s00134-008-1368-1 CrossRefPubMedGoogle Scholar
  23. 23.
    Barraud D, Blard C, Hein F, Marçon O, Cravoisy A, Nace L et al (2010) Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care Med 36:1540–1547. doi: 10.1007/s00134-010-1927-0 CrossRefPubMedGoogle Scholar
  24. 24.
    Oudhuis GJ, Bergmans DC, Dormans T, Zwaveling JH, Kessels A, Prins MH et al (2011) Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality. Intensive Care Med 37:110–117. doi: 10.1007/s00134-010-2002-6 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    [No authors listed] (2015) Randomized controlled study of probiotics containing Lactobacillus casei (Shirota strain) for prevention of ventilator-associated pneumonia. J Med Assoc Thai 98:253–259Google Scholar
  26. 26.
    Sommacal HM, Bersch VP, Vitola SP, Osvaldt AB (2015) Perioperative synbiotics decrease postoperative complications in periampullary neoplasms: a randomized, double-blind clinical trial. Nutr Cancer 67:457–462. doi: 10.1080/01635581.2015.1004734 CrossRefPubMedGoogle Scholar
  27. 27.
    Falcão de Arruda IS, de Aguilar-Nascimento JE (2004) Benefits of early enteral nutrition with glutamine and probiotics in brain injury patients. Clin Sci (Lond) 106:287–292. doi: 10.1042/CS20030251 CrossRefGoogle Scholar
  28. 28.
    de Araujo GV, de Oliveira Junior MH, Peixoto DM, Sarinho ES (2015) Probiotics for the treatment of upper and lower respiratory-tract infections in children: systematic review based on randomized clinical trials. J Pediatr (Rio J). 91:413–427. doi: 10.1016/j.jped.2015.03.002 CrossRefGoogle Scholar
  29. 29.
    Lone NI, Walsh TS (2011) Prolonged mechanical ventilation in critically ill patients: epidemiology, outcomes and modelling the potential cost consequences of establishing a regional weaning unit. Crit Care 15:R102. doi: 10.1186/cc10117 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ego A, Preiser JC, Vincent JL (2015) Impact of diagnostic criteria on the incidence of ventilator-associated pneumonia. Chest 147:347–355. doi: 10.1378/chest.14-0610 CrossRefPubMedGoogle Scholar
  31. 31.
    Scholte JB, van Dessel HA, Linssen CF, Bergmans DC, Savelkoul PH, Roekaerts PM et al (2014) Endotracheal aspirate and bronchoalveolar lavage fluid analysis: interchangeable diagnostic modalities in suspected ventilator-associated pneumonia? J Clin Microbiol 52:3597–3604. doi: 10.1128/JCM.01494-14 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Wang J, Liu KX, Ariani F, Tao LL, Zhang J, Qu JM (2013) Probiotics for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of high-quality randomized controlled trials. PLoS One 8:e83934. doi: 10.1371/journal.pone.0083934 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Luyer MD, Buurman WA, Hadfoune M, Speelmans G, Knol J, Jacobs JA et al (2005) Strain-specific effects of probiotics on gut barrier integrity following hemorrhagic shock. Infect Immun 73:3686–3692. doi: 10.1128/IAI.73.6.3686-3692.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hurley JC (2008) Profound effect of study design factors on ventilator-associated pneumonia incidence of prevention studies: benchmarking the literature experience. J Antimicrob Chemother 61:1154–1161. doi: 10.1093/jac/dkn086 CrossRefPubMedGoogle Scholar
  35. 35.
    Jain PK, McNaught CE, Anderson AD, MacFie J, Mitchell CJ (2004) 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 23:467–475. doi: 10.1016/j.clnu.2003.12.002 CrossRefPubMedGoogle Scholar
  36. 36.
    Bekaert M, Timsit JF, Vansteelandt S, Depuydt P, Vésin A, Garrouste-Orgeas M et al (2011) Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med 184:1133–1139. doi: 10.1164/rccm.201105-0867OC CrossRefPubMedGoogle Scholar
  37. 37.
    Loss SH, de Oliveira RP, Maccari JG, Savi A, Boniatti MM, Hetzel MP et al (2015) The reality of patients requiring prolonged mechanical ventilation: a multicenter study. Rev Bras Ter Intensiva 27:26–35. doi: 10.5935/0103-507X.20150006 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Hashimoto S, Shime N (2013) Evaluation of semi-quantitative scoring of Gram staining or semi-quantitative culture for the diagnosis of ventilator-associated pneumonia: a retrospective comparison with quantitative culture. J Intensive Care 1:2. doi: 10.1186/2052-0492-1-2 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Niederman MS (2010) The argument against using quantitative cultures in clinical trials and for the management of ventilator-associated pneumonia. Clin Infect Dis 51[Suppl 1]:S93–S99. doi: 10.1086/653055 CrossRefPubMedGoogle Scholar
  40. 40.
    Berton DC, Kalil AC, Teixeira PJ (2014) Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev 10:006482. doi: 10.1002/14651858.CD006482.pub4 Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2016

Authors and Affiliations

  • Juan Zeng
    • 1
  • Chun-Ting Wang
    • 1
  • Fu-Shen Zhang
    • 2
  • Feng Qi
    • 2
  • Shi-Fu Wang
    • 3
  • Shuang Ma
    • 3
  • Tie-Jun Wu
    • 4
  • Hui Tian
    • 4
  • Zhao-Tao Tian
    • 5
  • Shu-Liu Zhang
    • 5
  • Yan Qu
    • 6
  • Lu-Yi Liu
    • 7
  • Yuan-Zhong Li
    • 8
  • Song Cui
    • 8
  • He-Ling Zhao
    • 9
  • Quan-Sheng Du
    • 9
  • Zhuang Ma
    • 10
  • Chun-Hua Li
    • 10
  • Yun Li
    • 11
  • Min Si
    • 11
  • Yu-Feng Chu
    • 1
  • Mei Meng
    • 1
  • Hong-Sheng Ren
    • 1
  • Ji-Cheng Zhang
    • 1
  • Jin-Jiao Jiang
    • 1
  • Min Ding
    • 1
  • Yu-Ping Wang
    • 1
  1. 1.Department of Intensive Care UnitShandong Provincial Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China
  2. 2.Department of Intensive Care UnitTaian Central HospitalTaianPeople’s Republic of China
  3. 3.Department of Intensive Care UnitZibo Central HospitalZiboPeople’s Republic of China
  4. 4.Department of Intensive Care UnitLiaocheng People’s HospitalLiaochengPeople’s Republic of China
  5. 5.Department of Intensive Care UnitJinan Military General HospitalJinanPeople’s Republic of China
  6. 6.Department of Intensive Care UnitQingdao Municipal HospitalQingdaoPeople’s Republic of China
  7. 7.Department of Intensive Care UnitYantai Yuhuangding HospitalYantaiPeople’s Republic of China
  8. 8.Department of Intensive Care UnitDalian Central HospitalDalianPeople’s Republic of China
  9. 9.Department of Intensive Care UnitHebei People’s HospitalShijiazhuangPeople’s Republic of China
  10. 10.Department of Intensive Care UnitGeneral Hospital of Shenyang Military RegionShenyangPeople’s Republic of China
  11. 11.Department of Intensive Care UnitJinan Central HospitalJinanPeople’s Republic of China

Personalised recommendations