June 9, 2016

Results from a multicentre randomised controlled trial

Results from a multicentre randomised controlled trial


Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in ICU with reported incidence of up to 78%. The mechanisms for development of VAP involve the colonisation of bacteria of the upper respiratory tract with subsequent aspiration into the lower respiratory tract. One potential source is the upper digestive tract in particular with the ongoing use of peptic ulcer prophylaxis. Hence, strategies to modulate bacterial flora to reduce the burden of potentially pathogenic microorganisms (PPMOs) has been investigated for decades, e.g. selective decontamination of the digestive tract. Zeng and colleagues investigate whether the administration of probiotics can reduce the incidence of VAP. 

Design: Prospective, open-label, multi-centre, controlled, and randomised trial with 235 patients enrolled from 9 centres caring for a mixed ICU population. Inclusion criteria included those patients requiring mechanical ventilation (MV) for greater than 48 hours. Relevant exclusion criteria included:

  • Age of <18 years or >80 years
  • Acute Physiology and Chronic Health Evaluation (APACHE) II score of ≥25
  • Mechanical ventilation for >72 h prior to enrollment
  • Failure of enteral feeding
  • Administration of immunodepressants 1 week before enrollment

Intervention: Open-label comparison with a 1:1 randomisation with Probiotic or no probiotic (each capsule contained active Bacillus subtilis and Enterococcus faecalis).

Outcome measures:

  • Presence of VAP through clinical diagnosis
  • PPMO colonisation of the oropharynx and stomach


  • Number of ventilated days
  • Duration of antibiotic use
  • Number of days in ICU and hospital
  • ICU and hospital mortality

Probiotic administration resulted in:

  • A significant reduction in the diagnosis of microbiologically confirmed VAP, as compared with the control group (36.4% vs 50.4%; P<0.05)
  • A trend towards a reduction in the incidence of clinically diagnosed VAP (40.7% vs 53.0%; P=0.059)
  • A delayed onset of first VAP development after tracheal intubation ((7.5 vs. 10.4 days; P = 0.022)
  • Significantly higher likelihood of remaining VAP free during the study period (P=0.004) with a relative risk reduction of 28% and absolute risk reduction of 14% (NNT to prevent one episode of VAP was 7)
  • No differences in eradication of colonisation of PPMOs in the oropharynx or stomach.
  • A significant reduction in the acquisition of PPMOs in patients who had no colonisation prior to administration (24% vs. 44%; P=0.004)
  • Conclusions:

This study performed by Zeng et al. significantly contributes to the literature surrounding the use of probiotics in VAP prevention. Indeed, there is a significant reduction in microbiologically confirmed VAP with a tendency towards reduction in clinically diagnosed VAP. The delay in first VAP episode possibly through the reduction in the acquisition of PPMOs is an important observation. Given the excellent safety profile of probiotic use, the implementation of such simple measures may show significant benefit. Further large-scale trials may allow more disseminated use of such interventions. Further studies should provide insights into the mechanisms of how different types of probiotics may influence specific PPMOs to provide a more personalised approach.

Article review was submitted by Brijesh Patel on behalf of the ESICM NEXT Committee.


Zeng et al. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomised controlled multicentre trial. Intensive Care Medicine. Original, Volume 42, Issue 6 / June, 2016, Pages 1018 – 1028.


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