title: Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study.
abstract: BACKGROUND
  The incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.
  
  
  METHODS
  A retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher's exact test while the student's t-test or Mann-Whitney U test were used for continuous variables.
  
  
  RESULTS
  Ninety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033).
  
  
  CONCLUSIONS
  Addition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA. claire.murphy@osumc.edu.
authors.forename: Neha M
authors.initials: NM
authors.lastname: Doshi
authors.forename: Charles H
authors.initials: CH
authors.lastname: Cook
authors.forename: Kari L
authors.initials: KL
authors.lastname: Mount
authors.forename: Stanislaw P
authors.initials: SP
authors.lastname: Stawicki
authors.forename: Erin N
authors.initials: EN
authors.lastname: Frazee
authors.forename: Heather A
authors.initials: HA
authors.lastname: Personett
authors.forename: Garrett E
authors.initials: GE
authors.lastname: Schramm
authors.forename: Heather M
authors.initials: HM
authors.lastname: Arnold
authors.forename: Claire V
authors.initials: CV
authors.lastname: Murphy