Azithromycin as a Quorum-Sensing Inhibitor for the Prevention of Pseudomonas Aeruginosa Ventilator-Associated Pneumonia

Proof of Concept Study to Investigate the Impact of Azithromycin Administered iv Versus Placebo on the Prevention of Pneumonia in Ventilated Patients Colonized by Pseudomonas Aeruginosa

The purpose of this study is to assess the clinical efficacy of azithromycin, used as a quorum-sensing blocker, when compared to placebo for preventing or delaying the occurrence of pneumonia in ventilated patients colonized with Pseudomonas aeruginosa.

Inclusion Criteria:

• Male and non pregnant female aged 18 to 75 years
• Patients hospitalized in ICU, under mechanically assisted ventilation expected to be mandatory for 3 days or more
• Reasonable survival chance within next few days with an Apache score 10-25
• Tracheal aspirate found positive for P. aeruginosa
• The subject (or a close family member in case of incompetence) understands the procedure, agrees to participate, and is willing to give written informed consent
• Informed consent must be obtained for all subjects before enrollment in the study, by patient or by a close family member

Exclusion Criteria:

• Poor prognosis as judged by Apache score II score >25
• Pregnant female
• Grossly under-or overweight (BMI<18or >29)
• Ongoing therapy with a macrolide
• Known allergy to any macrolide
• Proven P. aeruginosa pneumonia
• Ongoing anti-pseudomonal therapy with a proven susceptible colonizing strain
• Anticipated short duration of mechanical ventilation (<3 days)
• Known drug interaction that could either decrease efficacy or raise safety concerns
• Severe hepatic failure (type C, score >10 on Child Pugh scale)
• Sick sinus syndrome or long QT syndrome
• Recent donation of blood or participation in another clinical trial within 3 months
• Any situation exposing the patient to higher risk or possibly confounding results