title: Pseudomonas aeruginosa phenotypes associated with eradication failure in children with cystic fibrosis.
abstract: BACKGROUND
  Pseudomonas aeruginosa is a key respiratory pathogen in people with cystic fibrosis (CF). Due to its association with lung disease progression, initial detection of P. aeruginosa in CF respiratory cultures usually results in antibiotic treatment with the goal of eradication. Pseudomonas aeruginosa exhibits many different phenotypes in vitro that could serve as useful prognostic markers, but the relative relationships between these phenotypes and failure to eradicate P. aeruginosa have not been well characterized.
  
  
  METHODS
  We measured 22 easily assayed in vitro phenotypes among the baseline P. aeruginosa isolates collected from 194 participants in the 18-month EPIC clinical trial, which assessed outcomes after antibiotic eradication therapy for newly identified P. aeruginosa. We then evaluated the associations between these baseline isolate phenotypes and subsequent outcomes during the trial, including failure to eradicate after antipseudomonal therapy, emergence of mucoidy, and occurrence of an exacerbation.
  
  
  RESULTS
  Baseline P. aeruginosa isolates frequently exhibited phenotypes thought to represent chronic adaptation, including mucoidy. Wrinkly colony surface and irregular colony edges were both associated with increased risk of eradication failure (hazard ratios [95% confidence intervals], 1.99 [1.03-3.83] and 2.14 [1.32-3.47], respectively). Phenotypes reflecting defective quorum sensing were significantly associated with subsequent mucoidy, but no phenotype was significantly associated with subsequent exacerbations during the trial.
  
  
  CONCLUSIONS
  Pseudomonas aeruginosa phenotypes commonly considered to reflect chronic adaptation were observed frequently among isolates at early detection. We found that 2 easily assayed colony phenotypes were associated with failure to eradicate after antipseudomonal therapy, both of which have been previously associated with altered biofilm formation and defective quorum sensing.
authors.affiliation: Department of Pediatrics Department of Biostatistics Department of Seattle Children's Hospital, Washington.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Department of Pediatrics Department of Seattle Children's Hospital, Washington.
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
authors.affiliation: Department of Microbiology.
authors.forename: Hemantha D
authors.initials: HD
authors.lastname: Kulasekara
authors.affiliation: Department of Pediatrics.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wolter
authors.affiliation: Department of Pediatrics.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Houston
authors.affiliation: Department of Pediatrics.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pope
authors.affiliation: Department of Microbiology.
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Kulasekara
authors.affiliation: Department of Microbiology.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Armbruster
authors.affiliation: Department of Pediatrics Department of Seattle Children's Hospital, Washington.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
authors.affiliation: Department of Pediatrics, University of North Carolina, Chapel Hill.
authors.forename: George
authors.initials: G
authors.lastname: Retsch-Bogart
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 Microbiology Department of Genome Sciences Department of Medicine, University of Washington, Seattle.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.affiliation: Department of Seattle Children's Hospital, Washington.
authors.forename: Umer
authors.initials: U
authors.lastname: Khan
authors.affiliation: Department of Pediatrics Department of Microbiology Department of Seattle Children's Hospital, Washington.
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Hoffman
mesh_terms: D018441:Biofilms / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D005260:Female; D005838:Genotype; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology* / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017211:Treatment Failure
chemical_list: D006025:Glycosaminoglycans; C046129:mucoid exopolysaccharide (P aeruginosa)
keywords: Pseudomonas aeruginosa; antibiotic treatment; cystic fibrosis; eradication; phenotypic characterization