Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis

Am J Respir Crit Care Med. 2003 Mar 15;167(6):841-9. doi: 10.1164/rccm.200208-855OC. Epub 2002 Dec 12.

Abstract

We conducted a double-blind, placebo-controlled, multicenter, randomized trial to test the hypothesis that 300 mg of tobramycin solution for inhalation administered twice daily for 28 days would be safe and result in a profound decrease in Pseudomonas aeruginosa (Pa) density from the lower airway of young children with cystic fibrosis. Ninety-eight subjects were to be randomized; however, the trial was stopped early because of evidence of a significant microbiological treatment effect. Twenty-one children under age 6 years were randomized (8 active; 13 placebo) and underwent bronchoalveolar lavage at baseline and on Day 28. There was a significant difference between treatment groups in the reduction in Pa density; no Pa was detected on Day 28 in 8 of 8 active group patients compared with 1 of 13 placebo group patients. We observed no differences between treatment groups for clinical indices, markers of inflammation, or incidence of adverse events. No abnormalities in serum creatinine or audiometry and no episodes of significant bronchospasm were observed in association with active treatment. We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Age Factors
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacology
  • Audiometry
  • Bronchoalveolar Lavage Fluid / microbiology
  • Carrier State / diagnosis
  • Carrier State / drug therapy*
  • Child, Preschool
  • Creatinine / blood
  • Cystic Fibrosis / blood
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / genetics
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Monitoring
  • Female
  • Genotype
  • Hearing Disorders / chemically induced
  • Hearing Disorders / diagnosis
  • Humans
  • Kidney Diseases / chemically induced
  • Kidney Diseases / diagnosis
  • Male
  • Oropharynx / microbiology
  • Pseudomonas Infections / diagnosis
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / etiology*
  • Pseudomonas aeruginosa*
  • Respiratory Tract Infections / diagnosis
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / etiology*
  • Safety
  • Severity of Illness Index
  • Sputum / microbiology
  • Tobramycin / administration & dosage*
  • Tobramycin / blood
  • Tobramycin / pharmacology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Creatinine
  • Tobramycin