Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial
Intensive Care Medicine, 04/30/2012
van Delden C et al. – There was a trend towards reduced incidence of ventilator–associated pneumonia (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.Methods
- In a randomized, double–blind, multicenter trial, intubated colonized patients received either 300mg/day azithromycin or placebo.
- Primary endpoint was the occurrence of P. aeruginosa VAP.
- The authors 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.
- 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).