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


OBJECTIVE
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.


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.
Kollef
Marin
M
Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8052, St. Louis, MO 63110, USA. mkollef@im.wustl.edu
Pittet
Didier
D
Sánchez García
Miguel
M
Chastre
Jean
J
Fagon
Jean-Yves
JY
Bonten
Marc
M
Hyzy
Robert
R
Fleming
Thomas R
TR
Fuchs
Henry
H
Bellm
Lisa
L
Mercat
Alain
A
Mañez
Rafael
R
Martínez
Antonio
A
Eggimann
Philippe
P
Daguerre
Martín
M
Luyt
Charles-Edouard
CE
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000627:therapeutic use; D011014:Pneumonia / Q000209:etiology / Q000517:prevention & control*; D012121:Respiration, Artificial / Q000009:adverse effects*; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C119872:antimicrobial peptide IB-367