title: Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.
abstract: BACKGROUND
  Colistin often remains the only active agent against multidrug-resistant Gram-negative pathogens. The aim of the study was to assess efficacy of nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.
  
  
  METHODS
  One hundred and sixty-five patients with VAP caused by P. aeruginosa and A. baumannii were enrolled in a prospective, observational, and comparative study. The sensitive strain group included 122 patients with VAP caused by P. aeruginosa and A. baumannii susceptible to β-lactams, aminoglycosides, or quinolones and treated with intravenous antibiotics for 14 days. The multidrug-resistant strain group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa and A. baumannii and treated with nebulized colistin (5 million international units every 8 h) either in monotherapy (n=28) or combined to a 3-day intravenous aminoglycosides for 7-19 days. The primary endpoint was clinical cure rate. Aerosol was delivered using vibrating plate nebulizer.
  
  
  RESULTS
  After treatment, clinical cure rate was 66% in sensitive strain group and 67% in multidrug-resistant strain group (difference -1%, lower limit of 95% CI for difference -12.6%). Mortality was not different between groups (23 vs. 16%). Among 16 patients with persisting or recurrent P. aeruginosa infection, colistin minimum inhibitory concentration increased in two patients.
  
  
  CONCLUSIONS
  Nebulization of high-dose colistin was effective to treat VAP caused by multidrug-resistant P. aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous β-lactams associated with aminoglycosides or quinolones for treating VAP caused by susceptible P. aeruginosa and A. baumannii.
authors.affiliation: Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance-Publique-Hôpitaux-de-Paris, UPMC Univ, Paris, France. qin.lu@psl.aphp.fr
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.forename: Rubin
authors.initials: R
authors.lastname: Luo
authors.forename: Liliane
authors.initials: L
authors.lastname: Bodin
authors.forename: Jianxin
authors.initials: J
authors.lastname: Yang
authors.forename: Noël
authors.initials: N
authors.lastname: Zahr
authors.forename: Alexandra
authors.initials: A
authors.lastname: Aubry
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Golmard
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Rouby
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000473:pathology; D040981:Acinetobacter baumannii / Q000302:isolation & purification*; D000328:Adult; D000368:Aged; D003091:Colistin / Q000008:administration & dosage*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D016896:Treatment Outcome
chemical_list: D003091:Colistin