title: A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia.
abstract: 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.
authors.affiliation: Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8052, St. Louis, MO 63110, USA. mkollef@im.wustl.edu
authors.forename: Marin
authors.initials: M
authors.lastname: Kollef
authors.forename: Didier
authors.initials: D
authors.lastname: Pittet
authors.forename: Miguel
authors.initials: M
authors.lastname: Sánchez García
authors.forename: Jean
authors.initials: J
authors.lastname: Chastre
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Fagon
authors.forename: Marc
authors.initials: M
authors.lastname: Bonten
authors.forename: Robert
authors.initials: R
authors.lastname: Hyzy
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.forename: Henry
authors.initials: H
authors.lastname: Fuchs
authors.forename: Lisa
authors.initials: L
authors.lastname: Bellm
authors.forename: Alain
authors.initials: A
authors.lastname: Mercat
authors.forename: Rafael
authors.initials: R
authors.lastname: Mañez
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez
authors.forename: Philippe
authors.initials: P
authors.lastname: Eggimann
authors.forename: Martín
authors.initials: M
authors.lastname: Daguerre
authors.forename: Charles-Edouard
authors.initials: CE
authors.lastname: Luyt
mesh_terms: 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
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C119872:antimicrobial peptide IB-367