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Probiotics for Prevention of Ventilator-Associated PneumoniaProbiotics for Ventilator-Associated Pneumonia FREE TO VIEW

Ilias I. Siempos, MD; Theodora K. Ntaidou, MD
Author and Funding Information

From the Critical Care Department (Dr Siempos), “Attikon” Hospital, University of Athens-Medical School; and the Department of Anaesthesia (Dr Ntaidou), Royal Brompton and Harefield NHS Foundation Trust.

Correspondence to: Ilias I. Siempos, MD, “Attikon” University Hospital, 1 Rimini St, 124 62 Haidari, Greece; e-mail: isiempos@yahoo.com


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(4):1185-1186. doi:10.1378/chest.12-2506
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Published online
To the Editor:

We compliment Gu et al1 in a recent issue of CHEST (October 2012) for their attempt to evaluate the effectiveness of probiotics for the prevention of ventilator-associated pneumonia (VAP) by performing a meta-analysis of randomized controlled trials (RCTs). However, we strongly disagree with the definitive tone of the title of their article. We believe that the limited evidence and several methodologic issues related to their contribution do not justify such strong conclusions.

Firstly, the authors failed to include in their meta-analysis a relevant RCT2 that apparently met their inclusion criteria. In that RCT, Tan et al2 administered probiotics to traumatic brain-injured patients and found that VAP developed in 44% of probiotic recipients vs 68% of control patients. Secondly, Gu et al1 did not include in their review another relevant RCT (by Spindler-Vesel et al3), arguing that it “provided data on pneumonia, which did not meet the criteria of being ventilator-associated.”1 Their argument is unsatisfactory because that RCT referred to pneumonia that occurred in multiple injured patients under mechanical ventilation hospitalized for at least 4 days in a surgical ICU.3 Not surprisingly, this second RCT3 was included in previous relevant meta-analyses.4,5 Thirdly, one could question the choice of the authors to implement a random effects model despite the fact that they found only low heterogeneity among the included studies.1 Implementation of a fixed effect model and the addition of the two RCTs2,3 to the meta-analysis would reveal a statistical significance (ie, probiotics decrease the incidence of VAP [pooled OR, 0.74; 95% CI, 0.55-0.98]) (Fig 1).

Figure Jump LinkFigure 1. Meta-analysis of randomized controlled trials evaluating the effects of probiotics on the incidence of ventilator-associated pneumonia. Vertical line=“no difference” point between the two regimens; ▪=OR (the size of each square denotes the proportion of information given by each trial); ◆=pooled OR for all randomized controlled trials; horizontal lines=95% CI. df=degrees of freedom.Grahic Jump Location

Over the past few months, two additional meta-analyses exploring the role of probiotics in preventing VAP and/or hospital-acquired pneumonia have been published,4,13 in addition to the meta-analysis by Gu et al.1 The more recent revealed that probiotics are beneficial against VAP,13 whereas the other noted that probiotics are beneficial against hospital-acquired pneumonia (but not against VAP).4 Revealing or not, a statistical significance in a meta-analysis depends on the choice of included RCTs. However, all recent meta-analyses1,4,13 and a previous one5 agree that the association between the administration of probiotics and the prevention of VAP has, indeed, clinical significance; an approximately 20% decrease in the incidence of pneumonia has been reported consistently. With the previous considerations in mind, we believe that the administration of probiotics may be valuable in managing critically ill patients and that its “condemnation” should be carefully thought out.

References

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(4):859-868. [CrossRef] [PubMed]
 
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(6):R290. [CrossRef] [PubMed]
 
Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. JPEN J Parenter Enteral Nutr. 2007;31(2):119-126. [CrossRef] [PubMed]
 
Liu KX, Zhu YG, Zhang J, et al. Probiotics’ effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis. Crit Care. 2012;16(3):R109. [CrossRef] [PubMed]
 
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(3):954-962. [CrossRef] [PubMed]
 
Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C. Oral probiotic and prevention ofPseudomonas aeruginosainfections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care. 2008;12(3):R69. [CrossRef] [PubMed]
 
Klarin B, Molin G, Jeppsson B, Larsson A. 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. 2008;12(6):R136. [CrossRef] [PubMed]
 
Knight DJ, Gardiner D, Banks A, et al. 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(5):854-861. [CrossRef] [PubMed]
 
Giamarellos-Bourboulis EJ, Bengmark S, Kanellakopoulou K, Kotzampassi K. Pro- and synbiotics to control inflammation and infection in patients with multiple injuries. J Trauma. 2009;67(4):815-821. [CrossRef] [PubMed]
 
Barraud D, Blard C, Hein F, et al. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. IntensiveCare Med. 2010;36(9):1540-1547. [CrossRef] [PubMed]
 
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(8):1058-1064. [CrossRef] [PubMed]
 
Oudhuis GJ, Bergmans DC, Dormans T, et al. Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality. Intensive Care Med. 2011;37(1):110-117. [CrossRef] [PubMed]
 
Petrof EO, 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(12):3290-3302. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Meta-analysis of randomized controlled trials evaluating the effects of probiotics on the incidence of ventilator-associated pneumonia. Vertical line=“no difference” point between the two regimens; ▪=OR (the size of each square denotes the proportion of information given by each trial); ◆=pooled OR for all randomized controlled trials; horizontal lines=95% CI. df=degrees of freedom.Grahic Jump Location

Tables

References

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(4):859-868. [CrossRef] [PubMed]
 
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(6):R290. [CrossRef] [PubMed]
 
Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. JPEN J Parenter Enteral Nutr. 2007;31(2):119-126. [CrossRef] [PubMed]
 
Liu KX, Zhu YG, Zhang J, et al. Probiotics’ effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis. Crit Care. 2012;16(3):R109. [CrossRef] [PubMed]
 
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(3):954-962. [CrossRef] [PubMed]
 
Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C. Oral probiotic and prevention ofPseudomonas aeruginosainfections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care. 2008;12(3):R69. [CrossRef] [PubMed]
 
Klarin B, Molin G, Jeppsson B, Larsson A. 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. 2008;12(6):R136. [CrossRef] [PubMed]
 
Knight DJ, Gardiner D, Banks A, et al. 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(5):854-861. [CrossRef] [PubMed]
 
Giamarellos-Bourboulis EJ, Bengmark S, Kanellakopoulou K, Kotzampassi K. Pro- and synbiotics to control inflammation and infection in patients with multiple injuries. J Trauma. 2009;67(4):815-821. [CrossRef] [PubMed]
 
Barraud D, Blard C, Hein F, et al. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. IntensiveCare Med. 2010;36(9):1540-1547. [CrossRef] [PubMed]
 
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(8):1058-1064. [CrossRef] [PubMed]
 
Oudhuis GJ, Bergmans DC, Dormans T, et al. Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality. Intensive Care Med. 2011;37(1):110-117. [CrossRef] [PubMed]
 
Petrof EO, 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(12):3290-3302. [CrossRef] [PubMed]
 
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