Probiotics for preventing ventilator-associated pneumonia

Review question

To critically assess the current evidence from published studies relating to the effect of probiotics for preventing ventilator-associated pneumonia (VAP).

Background

VAP is a condition that can occur in patients who have been mechanically ventilated for more than 48 hours and can significantly increase the likelihood of death within intensive care unit (ICU) patients. Despite the use of preventive measures and advances in antimicrobial therapy, VAP is the second most common hospital-related infection in the USA. It is associated with an increased chance of disease and death, and increased healthcare costs. It is believed that probiotics can reinforce the gut barrier function, which may result in clinical benefits. However, until now, there has been no clear evidence to determine whether probiotics are associated with better clinical outcomes.

Study characteristics

We identified eight studies with 1083 participants comparing probiotics versus placebo for preventing VAP. The studies were conducted between 2006 and 2011 in China, France, Greece, Slovenia, Sweden, the UK and the USA, with funding from various sources including hospital/National Health Service, pharmaceuticals and the National Institutes of Health. In the studies that stated the gender ratios, there were 611 males and 378 females. The evidence is current to September 2014.

Key results and quality of the evidence

The results from these trials show that probiotics are associated with a reduction in instances 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. Results for all remaining reported outcomes (including mortality, incidence of diarrhoea, length of ICU stay, duration of mechanical ventilation and general antibiotic use) were uncertain between groups receiving either probiotics or placebo or standard treatment. Incidence of diarrhoea was reported in half of the included studies, which demonstrated no clear evidence of a difference between probiotics over standard care or placebo. The quality of the evidence was generally low to very low between studies. Due to the contradictions in the results from previously published systematic reviews and the uncertainty of these results, there is need for larger, well-designed and robustly reported studies.

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.

Read the full 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 strategy: 

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.

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