title: Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria.
abstract: BACKGROUND
  The increasing frequency of ventilator-associated pneumonia (VAP) caused by colistin-only susceptible (COS) gram-negative bacteria (GNB) is of great concern. Adjunctive aerosolized (AS) colistin can reportedly increase alveolar levels of the drug without increasing systemic toxicity. Good clinical results have been obtained in patients with cystic fibrosis, but conflicting data have been reported in patients with VAP.
  
  
  METHODS
  We conducted a retrospective, 1:1 matched case-control study to evaluate the efficacy and safety of AS plus IV colistin vs IV colistin alone in 208 patients in the ICU with VAP caused by COS Acinetobacter baumannii, Pseudomonas aeruginosa, or Klebsiella pneumoniae.
  
  
  RESULTS
  Compared with the IV colistin cohort, the AS-IV colistin cohort had a higher clinical cure rate (69.2% vs 54.8%, P = .03) and required fewer days of mechanical ventilation after VAP onset (8 days vs 12 days, P = .001). In the 166 patients with posttreatment cultures, eradication of the causative organism was also more common in the AS-IV colistin group (63.4% vs 50%, P = .08). No between-cohort differences were observed in all-cause ICU mortality, length of ICU stay after VAP onset, or rates of acute kidney injury (AKI) during colistin therapy. Independent predictors of clinical cure were trauma-related ICU admission (P = .01) and combined AS-IV colistin therapy (P = .009). Higher mean Simplified Acute Physiology Score II (P = .002) and Sequential Organ Failure Assessment (P = .05) scores, septic shock (P &lt; .001), and AKI onset during colistin treatment (P = .04) were independently associated with clinical failure.
  
  
  CONCLUSIONS
  Our results suggest that AS colistin might be a beneficial adjunct to IV colistin in the management of VAP caused by COS GNB.
authors.affiliation: Institute of Infectious Diseases, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: tumbarello@rm.unicatt.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Tumbarello
authors.affiliation: Department of Intensive Care and Anesthesiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Pascale
authors.affiliation: Department of Intensive Care and Anesthesiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Trecarichi
authors.affiliation: Department of Intensive Care and Anesthesiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Martino
authors.affiliation: Department of Intensive Care and Anesthesiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bello
authors.affiliation: Department of Intensive Care and Anesthesiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Maviglia
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Spanu
authors.affiliation: Department of Intensive Care and Anesthesiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Antonelli
mesh_terms: D040981:Acinetobacter baumannii / Q000302:isolation & purification; D000280:Administration, Inhalation; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016022:Case-Control Studies; D003091:Colistin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D003422:Critical Care; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification*; D006801:Humans; D007275:Injections, Intravenous; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D061214:Patient Safety; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012189:Retrospective Studies; D016896:Treatment Outcome; D012122:Ventilators, Mechanical / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin