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Wan-Jie Gu, MSc; Rui-Xing Yin, MD, PhD
Author and Funding Information

From the Department of Cardiology (Mr Gu and Dr Yin), Institute of Cardiovascular Diseases, and Department of Anaesthesiology (Mr Gu), The First Affiliated Hospital, Guangxi Medical University.

Correspondence to: Rui-Xing Yin, MD, PhD, Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Rd, Nanning 530021, Guangxi, China; e-mail: yinruixing@yahoo.com.cn


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.

Funding/Support: This study was supported by the Science Foundation of Guangxi Returned Oversea Scholars [No. 0991004].

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):1186-1187. doi:10.1378/chest.12-2559
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Published online
To the Editor:

We thank Drs Siempos and Ntaidou for their interest in our work1 and for their insightful comments. We would like to clarify several important points.

  • 1. We did not include the study conducted by Tan et al2 in our meta-analysis because not all of the patients in the study received mechanical ventilation (16 of 26 in the probiotic group and 19 of 26 in the control group). If this study had been included, the findings would not change, and probiotics do not significantly decrease the incidence of ventilator-associated pneumonia (VAP) (fixed-effects model OR, 0.80; 95% CI, 0.59-1.08).

  • 2. We did not include the trial conducted by Spindler-Vesel et al3 in our review because this study provided data on pneumonia that was not specified as being ventilator associated.

  • 3. The initial title of our article was “Efficacy and Safety of Probiotics in Preventing Ventilator-Associated Pneumonia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.” However, the reviewers believed that the present title would better reflect our findings, and we accepted their suggestion.

  • 4. We initially performed the statistical analyses using a fixed-effects model, with a random-effects model used in cases of significant heterogeneity (I2 >50%). However, the reviewers disagreed with such an approach, stating that all meta-analytic studies have heterogeneity and that it is simply a question of whether the study is big enough to find it. They suggested that we use a random-effects model in every case because this would result in a more robust (ie, conservative) analysis. We accepted their insightful suggestions.

  • 5. As for the two recent meta-analyses,4,5 both have their own flaws. The study by Liu et al4 focused on the effects of probiotics on nosocomial pneumonia rather than VAP. In the most recent meta-analysis by Petrof et al,5 the data on VAP in their Table 2 and Figure 2 were inconsistent; the data in Table 2 were correct, and the data in Figure 2 were wrong. Reassessment of the data shows that probiotics did not significantly decrease the incidence of VAP (pooled risk ratio, 0.81; 95% CI, 0.59-1.12; P= .2) (Fig 1).

Figure Jump LinkFigure 1. Meta-analysis of randomized controlled trials evaluating the effects of probiotics on the incidence of ventilator-associated pneumonia. RR = risk ratio.Grahic Jump Location

In summary, the current limited evidence precludes final verdicts and strong clinical recommendations. Further research on the use of probiotics for VAP prevention is warranted. Large rigorous multicenter trials will help to generate better estimates of the possible benefits and harm, confirming or refuting the findings from the present analysis.

Acknowledgments

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

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]
 
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]
 
Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006;30(10):1848-1855. [CrossRef] [PubMed]
 
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(3):R69. [CrossRef] [PubMed]
 
Besselink  MG, van Santvoort HC, Buskens E, et al. Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:651-659. [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]
 
Barraud D, Blard C, Hein F, et al. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care 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]
 

Figures

Figure Jump LinkFigure 1. Meta-analysis of randomized controlled trials evaluating the effects of probiotics on the incidence of ventilator-associated pneumonia. RR = risk ratio.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]
 
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]
 
Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006;30(10):1848-1855. [CrossRef] [PubMed]
 
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(3):R69. [CrossRef] [PubMed]
 
Besselink  MG, van Santvoort HC, Buskens E, et al. Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:651-659. [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]
 
Barraud D, Blard C, Hein F, et al. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care 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]
 
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