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Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial
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Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial
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Journal Article
Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial
2012
Overview
Purpose
Anti-virulence strategies have not been evaluated for the prevention of bacterial infections. Prolonged colonization of intubated patients with
Pseudomonas aeruginosa
isolates producing high-levels of the quorum sensing (QS)-regulated virulence factor rhamnolipids has been associated with ventilator-associated pneumonia (VAP). In this pathogen, azithromycin reduces QS-regulated virulence. We aimed to assess whether azithromycin could prevent VAP in patients colonized by rhamnolipids producing isolates.
Methods
In a randomized, double-blind, multicenter trial, intubated colonized patients received either 300 mg/day azithromycin or placebo. Primary endpoint was the occurrence of
P. aeruginosa
VAP. We further identified those patients persistently colonized by isolates producing high-levels of rhamnolipids and therefore at the highest risk to develop VAP linked to this QS-dependent virulence factor.
Results
Ninety-two patients were enrolled; 43 azithromycin-treated and 42 placebo patients were eligible for the per-protocol analysis. In the per-protocol population, the occurrence of
P. aeruginosa
VAP was reduced in the azithromycin group but without reaching statistical significance (4.7 vs. 14.3 % VAP,
p
= 0.156). QS-dependent virulence of colonizing isolates was similarly low in both study groups, and only five patients in each arm were persistently colonized by high-level rhamnolipids producing isolates. In this high-risk subgroup, the incidence of VAP was reduced fivefold in azithromycin versus placebo patients (1/5 vs. 5/5 VAP,
p
= 0.048).
Conclusions
There was a trend towards reduced incidence of VAP in colonized azithromycin-treated patients
.
In addition, azithromycin significantly prevented VAP in those patients at high risk of rhamnolipid-dependent VAP, suggesting that virulence inhibition is a promising anti-microbial strategy.
Publisher
Springer-Verlag,Springer,Springer Nature B.V
Subject
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Anti-Bacterial Agents - therapeutic use
/ Azithromycin - therapeutic use
/ Biological and medical sciences
/ Cloning
/ Emergency and intensive respiratory care
/ Female
/ Glycolipids - therapeutic use
/ Humans
/ Male
/ Medicine
/ Original
/ Pneumology/Respiratory System
/ Pneumonia, Ventilator-Associated - drug therapy
/ Pneumonia, Ventilator-Associated - microbiology
/ Pneumonia, Ventilator-Associated - prevention & control
/ Pseudomonas aeruginosa - drug effects
/ Pseudomonas aeruginosa - pathogenicity
/ Pseudomonas Infections - drug therapy
/ Pseudomonas Infections - microbiology
/ Pseudomonas Infections - prevention & control
/ Quorum Sensing - drug effects
