title: Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes.
abstract: BACKGROUND
  Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease.
  
  
  OBJECTIVE
  To characterize the relationships between in vitro P. aeruginosa phenotypes, infection stage, and clinical outcomes.
  
  
  METHODS
  A total of 649 children with CF and newly identified P. aeruginosa were followed for a median 5.4 years during which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro bacterial phenotypes were assessed among the isolates, including measures of motility, exoproduct production, colony morphology, growth, and metabolism.
  
  
  RESULTS
  P. aeruginosa phenotypes present at the time of culture were associated with both stage of infection (new onset, intermittent, or chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best distinguished infection stages: pyoverdine production (31% of new-onset cultures, 48% of intermittent, 69% of chronic) and reduced protease production (31%, 39%, and 65%, respectively). The best P. aeruginosa phenotypic predictors of subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95% confidence interval, 1.19-2.57) and reduced twitching motility (odds ratio, 1.43; 95% confidence interval, 1.11-1.84).
  
  
  CONCLUSIONS
  In this large epidemiologic study of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro phenotypes that best distinguished early and later infection stages. Among the many phenotypes tested, mucoidy and reduced twitching best predicted subsequent PE. These phenotypes indicate potentially useful prognostic markers of transition to chronic infection and advancing lung disease.
authors.affiliation: 1 Department of Pediatrics.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gibson
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
authors.forename: Hemantha D
authors.initials: HD
authors.lastname: Kulasekara
authors.forename: George Z
authors.initials: GZ
authors.lastname: Retsch-Bogart
authors.forename: Wayne
authors.initials: W
authors.lastname: Morgan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wolter
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pope
authors.forename: Laura S
authors.initials: LS
authors.lastname: Houston
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Kulasekara
authors.forename: Umer
authors.initials: U
authors.lastname: Khan
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Hoffman
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D016015:Logistic Models; D008297:Male; D015337:Multicenter Studies as Topic; D017063:Outcome Assessment, Health Care; D010641:Phenotype; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000235:genetics / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification
keywords: epidemiology; exacerbation; mucoid Pseudomonas aeruginosa; pulmonary function; risk factors