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Meta-Analysis
. 2014 Oct 25;2014(10):CD009066.
doi: 10.1002/14651858.CD009066.pub2.

Probiotics for preventing ventilator-associated pneumonia

Lulong Bo  1 , Jinbao Li, Tianzhu Tao, Yu Bai, Xiaofei Ye, Richard S Hotchkiss, Marin H Kollef, Neil H Crooks, Xiaoming Deng
Affiliations
Meta-Analysis

Probiotics for preventing ventilator-associated pneumonia

Lulong Bo et al. Cochrane Database Syst Rev. .

Abstract

Background: Ventilator-associated pneumonia (VAP) is common in intensive care units (ICUs). Some evidence indicates that probiotics may reduce the incidence of VAP. Several additional published studies have demonstrated that probiotics are safe and efficacious in preventing VAP in ICUs. We aimed to systematically summarise the results of all available data to generate the best evidence for the prevention of VAP.

Objectives: To evaluate the effectiveness and safety of probiotics for preventing VAP.

Search methods: We searched CENTRAL (2014, Issue 8), MEDLINE (1948 to September week 1, 2014) and EMBASE (2010 to September 2014).

Selection criteria: Randomised controlled trials (RCTs) comparing probiotics with placebo or another control (excluding RCTs that use probiotics in both study groups) to prevent VAP.

Data collection and analysis: Two review authors independently assessed eligibility and the quality of trials, and extracted data.

Main results: We included eight RCTs, with 1083 participants. All studies compared a form of probiotic (Lactobacillus casei rhamnosus; Lactobacillus plantarum; Synbiotic 2000FORTE; Ergyphilus; combination Bifidobacterium longum + Lactobacillus bulgaricus + Streptococcus thermophilus) versus a control group (placebo; glutamine; fermentable fibre; peptide; chlorhexidine). The analysis of all RCTs showed that the use of probiotics decreased the incidence of VAP (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.52 to 0.95, low quality evidence). However, the aggregated results were uncertain for ICU mortality (OR 0.84, 95% CI 0.58 to 1.22 very low quality evidence), in-hospital mortality (OR 0.78, 95% CI 0.54 to 1.14, very low quality evidence), incidence of diarrhoea (OR 0.72, 95% CI 0.47 to 1.09, very low quality evidence), length of ICU stay (mean difference (MD) -1.60, 95% CI -6.53 to 3.33, very low quality evidence), duration of mechanical ventilation (MD -6.15, 95% CI -18.77 to 6.47, very low quality evidence) and antibiotic use (OR 1.23, 95% CI 0.51 to 2.96, low quality evidence). Antibiotics for VAP were used for a shorter duration (in days) when participants received probiotics in one small study (MD -3.00, 95% CI -6.04 to 0.04). However, the CI of the estimated effect was too wide to exclude no difference with probiotics. There were no reported events of nosocomial probiotic infections in any included study.The overall methodological quality of the included studies, based on our 'Risk of bias' assessments, was moderate with half of the included studies rated as a 'low' risk of bias; however, we rated four included studies as a 'high' risk of bias across one or more of the domains. The study limitations, differences in probiotics administered and participants, and small sample sizes across the included studies mean that the power to detect a trend of overall effect may be limited and chance findings cannot be excluded.To explore the influence of some potential confounding factors in the studies, we conducted an intention-to-treat (ITT) analysis, which did not change the inference of per-protocol analysis. However, our sensitivity analysis did not indicate a significant difference between groups for instances of VAP.

Authors' conclusions: Evidence suggests that use of probiotics is associated with a reduction in the incidence of VAP. However, the quality of the evidence is low and the exclusion of the one study that did not provide a robust definition of VAP increased the uncertainty in this finding. The available evidence is not clear regarding a decrease in ICU or hospital mortality with probiotic use. Three trials reported on the incidence of diarrhoea and the pooled results indicate no clear evidence of a difference. The results of this meta-analysis do not provide sufficient evidence to draw conclusions on the efficacy and safety of probiotics for the prevention of VAP in ICU patients.

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Conflict of interest statement

Lulong Bo: none known. Jinbao Li: none known. Tianzhu Tao: none known. Yu Bai: none known. Xiaofei Ye: none known. Richard S Hotchkiss: none known. Marin H Kollef: Dr Kollef has done consulting work for Merck and Cubist and has provided lectures for Cubist and Hospira. Neil H Crooks: Dr Neil Crooks has been awarded internal and external funding for a pilot study on probiotics in the critical care population. The study is registered on the EudraCT database (No 2011‐002343‐99). Xiaoming Deng: none known.

Figures

1
1
Study flow diagram: 2014 search
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 1 Incidence of VAP.
1.2
1.2. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 2 ICU mortality.
1.3
1.3. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 3 Hospital mortality.
1.4
1.4. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 4 Diarrhoea.
1.5
1.5. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 5 Length of ICU stay (days).
1.7
1.7. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 7 Duration of mechanical ventilation (days).
1.9
1.9. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 9 Antibiotic use for VAP (days).
1.10
1.10. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 10 Antibiotic use.
1.11
1.11. Analysis
Comparison 1 Per‐protocol analysis: probiotics versus control, Outcome 11 Adverse events: nosocomial probiotic infection.
2.1
2.1. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 1 ITT analysis: incidence of VAP.
2.2
2.2. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 2 ITT analysis: ICU mortality.
2.3
2.3. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 3 ITT analysis: hospital mortality.
2.4
2.4. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 4 ITT analysis: diarrhoea.
2.5
2.5. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 5 ITT analysis: ICU stay.
2.6
2.6. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 6 ITT analysis: duration of mechanical ventilation (days).
2.7
2.7. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 7 ITT analysis: antibiotic use for VAP (days).
2.8
2.8. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 8 ITT: antibiotic use.
2.9
2.9. Analysis
Comparison 2 ITT analysis: probiotics versus control, Outcome 9 ITT analysis: adverse events: nosocomial probiotic infection.
3.1
3.1. Analysis
Comparison 3 Subgroup analysis of primary outcomes: probiotics versus control, Outcome 1 Incidence of VAP: probiotics versus control.
3.2
3.2. Analysis
Comparison 3 Subgroup analysis of primary outcomes: probiotics versus control, Outcome 2 Incidence of VAP: sensitivity analysis (probiotics applied solely to stomach).
3.3
3.3. Analysis
Comparison 3 Subgroup analysis of primary outcomes: probiotics versus control, Outcome 3 Incidence of VAP: sensitivity analysis (more than 1010 bacteria in one dose).
3.4
3.4. Analysis
Comparison 3 Subgroup analysis of primary outcomes: probiotics versus control, Outcome 4 Incidence of VAP: sensitivity analysis (probiotics applied twice daily).
See this image and copyright information in PMC

Comment in

References

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