Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis

Ronald L. Gibson, Julia Emerson, Nicole Mayer-Hamblett, Jane L. Burns, Sharon McNamara, Frank J. Accurso, Michael W. Konstan, Barbara A. Chatfield, George Retsch-Bogart, David A. Waltz, James Acton, Pamela Zeitlin, Peter Hiatt, Richard Moss, Judy Williams, Bonnie W. Ramsey

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: 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 Paeradication 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. Conclusion: TSI monotherapy is safe and can eradicate lower airway Pa for up to 3 months after treatment in young children with CF.

Original languageEnglish (US)
Pages (from-to)610-623
Number of pages14
JournalPediatric pulmonology
Volume42
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • Bronchoalveolar lavage
  • Children
  • Cystic fibrosis
  • Eradication
  • Pseudomonas

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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