A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia.

Abstract

RATIONALE:

Iseganan, an antimicrobial peptide, is active against aerobic and anaerobic gram-positive and gram-negative bacteria as well as fungi and yeasts. The drug has shown little resistance in vitro and to be safe and well tolerated in 800 patients with cancer treated for up to 6 wk.

OBJECTIVES:

To determine the efficacy of iseganan for the prevention of ventilator-associated pneumonia (VAP).

METHODS:

Mechanically ventilated patients in the United States and Europe were randomized to oral topical iseganan or placebo (1:1) and treated six times per day while intubated for up to 14 d. Patients were eligible if randomized within 24 h of intubation and estimated to survive and remain mechanically ventilated for 48 h or more. The primary efficacy endpoint of the study was VAP measured among survivors at Day 14.

MEASUREMENTS AND MAIN RESULTS:

A total of 709 patients were randomized and received at least one dose of study drug. The two groups were comparable at baseline except iseganan-treated patients were, on average, 3 yr older. The rate of VAP among survivors at Day 14 was 16% (45/282) in patients treated with iseganan and 20% (57/284) in those treated with placebo (p = 0.145). Mortality at Day 14 was 22.1% (80/362) in the iseganan group compared with 18.2% (63/347) in the placebo group (p = 0.206). No pattern of excess adverse events in the iseganan group compared with placebo was observed.

CONCLUSIONS:

Iseganan is not effective in improving outcome in patients on prolonged mechanical ventilation.

• Authors: Marin Kollef, Didier Pittet, Miguel Sánchez García, Jean Chastre, Jean-Yves Fagon, Marc Bonten, Robert Hyzy, Thomas R Fleming, Henry Fuchs, Lisa Bellm, Alain Mercat, Rafael Mañez, Antonio Martínez, Philippe Eggimann, Martín Daguerre, Charles-Edouard Luyt, Prevention of Pneumonia Study (POPS-1) Trial Group
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 173 Issue 1 Pg. 91-7 (Jan 01 2006) ISSN: 1073-449X [Print] United States
• PMID: 16192451 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Antimicrobial Cationic Peptides
• Peptides
• antimicrobial peptide IB-367

Topics

• Administration, Oral
• Administration, Topical
• Adult
• Aged
• Anti-Infective Agents (administration & dosage, therapeutic use)
• Antimicrobial Cationic Peptides
• Double-Blind Method
• Humans
• Male
• Middle Aged
• Peptides (administration & dosage, therapeutic use)
• Pneumonia (etiology, prevention & control)
• Respiration, Artificial (adverse effects)
• Treatment Outcome