title: Use of adjunctive aerosolized antimicrobial therapy in the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii ventilator-associated pneumonia.
abstract: BACKGROUND
  Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of Gram-negative ventilator-associated pneumonia (VAP), but little is known about their influence on clinical outcomes.
  
  
  OBJECTIVE
  To assess outcomes associated with AAA for the treatment of Pseudomonas  aeruginosa (PA) and Acinetobacter baumannii (AB) VAP.
  
  
  METHODS
  A retrospective, single-center cohort study at Barnes-Jewish Hospital in St Louis, Missouri. Consecutive subjects treated for bronchoalveolar lavage-confirmed PA or AB VAP between January 1, 2004 and December 31, 2009  were enrolled. Records of subjects treated with AAA were compared to those who did not receive AAAs (NAAA).
  
  
  RESULTS
  Ninety-three patients were evaluated (NAAA n = 74, AAA n = 19, inhaled colistin n = 9, inhaled tobramycin n = 10). Patients receiving AAA were significantly  more likely to be infected with multidrug-resistant bacteria (52.6% vs 14.9%, P < .001) and had greater Acute Physiology and Chronic Health Evaluation II scores (21.4 ± 5.7 vs 17.5 ± 5.3, P = .004) compared to patients receiving NAAA. NAAA subjects experienced  a shorter time from VAP onset to appropriate intravenous antibiotic initiation (0.5 ± 0.9 d vs 2.6 ± 5.4 d, P = .038), but length of intravenous therapy was similar between groups (12.8 ± 8.5 d vs 17.8 ± 13.3 d, P = .16). The NAAA group demonstrated  significantly shorter mechanical ventilation duration (18.9 ± 15.9 d vs 38.4 ± 32.4 days, P < .001), intensive care unit stay (37.5 ± 42.5 d vs 56.3 ± 31.3 d, P = .001), and hospital stay (39.0 ± 42.5 d vs 58.3 ± 33.4 d, P =  .001). However, Kaplan-Meier curves for the probability of 30-day survival from VAP onset demonstrated that patients receiving AAA had statistically greater survival (P = .030 by the log rank test).
  
  
  CONCLUSIONS
  Patients with PA and AB VAP may experience favorable survival when treated  with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.
authors.affiliation: Department of Pharmacy, Barnes-Jewish Hospital, St Louis, Missouri, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Arnold
authors.forename: Amber M
authors.initials: AM
authors.lastname: Sawyer
authors.forename: Marin H
authors.initials: MH
authors.lastname: Kollef
mesh_terms: D018806:APACHE; D000151:Acinetobacter Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000302:isolation & purification; D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018893:Bronchoalveolar Lavage; D003091:Colistin / Q000008:administration & dosage / Q000627:therapeutic use*; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D014031:Tobramycin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D014031:Tobramycin; D003091:Colistin