title: Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long-term Outcomes in Cystic Fibrosis.
abstract: BACKGROUND
  Pseudomonas aeruginosa (Pa) is the most important pathogen infecting the airways in individuals with cystic fibrosis. A key question is whether children with newly acquired Pa infection who are able to achieve sustained eradication after early antipseudomonal therapy demonstrate improved long-term health outcomes compared with those who are unable to achieve a sustained microbiologic response.
  
  
  METHODS
  This cohort study utilized observational follow-up data on children participating in the Early Pseudomonas Infection Control trial who received standardized therapy for newly acquired Pa. Sustained eradicators were defined as those who maintained Pa-negative cultures for 12 months after initial antipseudomonal therapy. Associations between eradication status and outcomes were assessed.
  
  
  RESULTS
  Of the 249 trial participants included in the study, 172 (69%) achieved sustained eradication of Pa during the trial (sustained eradicators). Over the median 5-year follow-up, sustained eradicators had a 74% reduced risk of developing chronic Pa (hazard ratio [HR], 0.26; 95% confidence interval [CI], .17-.40) and a 57% reduced risk of mucoidy (HR, 0.43; 95% CI, .25-.73) compared with nonsustained eradicators. Sustained eradicators had significantly less anti-Pa antibiotic usage during follow-up compared with nonsustained eradicators. There was no association between eradication status and clinical outcomes including rate of exacerbation and lung function decline.
  
  
  CONCLUSIONS
  This is the first study to quantify the long-term durability of microbiological response associated with early antipseudomonal therapy, demonstrating the critical importance of optimizing antipseudomonal therapies during early Pa infection. The clinical impact of failure to achieve sustained Pa eradication remains unclear, however, and may be confounded by anti-Pa antibiotic usage.
  
  
  BACKGROUND
  NCT00097773.
authors.affiliation: Department of Pediatrics Department of Biostatistics, University of Washington Department of Seattle Children's Hospital, Washington;
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Department of Seattle Children's Hospital, Washington;
authors.forename: Margaret
authors.initials: M
authors.lastname: Kloster
authors.affiliation: Department of Pediatrics Department of Seattle Children's Hospital, Washington;
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.affiliation: Department of Pediatrics Department of Seattle Children's Hospital, Washington;
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gibson
authors.affiliation: Department of Pediatrics, University of North Carolina at Chapel Hill.
authors.forename: George Z
authors.initials: GZ
authors.lastname: Retsch-Bogart
authors.affiliation: Department of Pediatrics Department of Seattle Children's Hospital, Washington;
authors.forename: Julia
authors.initials: J
authors.lastname: Emerson
authors.affiliation: Department of Seattle Children's Hospital, Washington;
authors.forename: Valeria
authors.initials: V
authors.lastname: Thompson
authors.affiliation: Department of Pediatrics Department of Seattle Children's Hospital, Washington;
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000453:epidemiology* / Q000382:microbiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology; D011550:Pseudomonas aeruginosa; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: Pseudomonas aeruginosa; Pseudomonas infections; cystic fibrosis; eradication therapy; treatment outcomes