title: Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis.
abstract: BACKGROUND
  Among young children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) airway infection is associated with increased morbidity and mortality. Early intervention strategies include tobramycin solution for inhalation (TSI), which can eradicate lower airway Pa from cultures obtained at the end of 28 days of treatment in young children.
  
  
  METHODS
  We conducted an open label, sequential cohort study of TSI in young children with CF to investigate duration of antimicrobial treatment effect. The primary outcome was lower airway Pa eradication per bronchoalveolar lavage (BAL) fluid culture. Sequential treatment cohorts varied by duration of treatment (28 or 56 days) and timing of follow-up BAL (at Days 56, 84, or 112). Subjects (N = 36) were treated with TSI, 300 mg twice daily, for 28 days or 56 days per cohort assignment.
  
  
  RESULTS
  Among 31 evaluable subjects, culture based, lower airway Pa eradication was observed in the majority of subjects for up to 1-3 months following TSI treatment: 75% in Cohort 28/56 (days of treatment/day of follow-up BAL), 63% in Cohort 28/84, 82% in Cohort 56/112, and 75% in Cohort 28/112. Non-mucoid Pa at baseline and/or exotoxin A seronegativity were associated with higher rates of eradication. There was a less pronounced effect of TSI treatment on Pa eradication from oropharyngeal cultures in all cohorts. TSI treatment was associated with reduced neutrophilic airway inflammation and was not related to any serious adverse events.
  
  
  CONCLUSIONS
  TSI monotherapy is safe and can eradicate lower airway Pa for up to 3 months after treatment in young children with CF.
authors.affiliation: Department of Pediatrics, University of Washington/Children's Hospital & Regional Medical Center, Seattle, WA 98105-0371, USA. ron.gibson@seattlechildrens.org
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gibson
authors.forename: Julia
authors.initials: J
authors.lastname: Emerson
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
authors.forename: Sharon
authors.initials: S
authors.lastname: McNamara
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Chatfield
authors.forename: George
authors.initials: G
authors.lastname: Retsch-Bogart
authors.forename: David A
authors.initials: DA
authors.lastname: Waltz
authors.forename: James
authors.initials: J
authors.lastname: Acton
authors.forename: Pamela
authors.initials: P
authors.lastname: Zeitlin
authors.forename: Peter
authors.initials: P
authors.lastname: Hiatt
authors.forename: Richard
authors.initials: R
authors.lastname: Moss
authors.forename: Judy
authors.initials: J
authors.lastname: Williams
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000209:etiology* / Q000517:prevention & control*; D012996:Solutions; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D012996:Solutions; D014031:Tobramycin