title: Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis.
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.
authors.affiliation: Department of Pediatrics, Children's Hospital and Regional Medical Center/University of Washington, Seattle, Washington 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: Sharon
authors.initials: S
authors.lastname: McNamara
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Ann
authors.initials: A
authors.lastname: Yunker
authors.forename: Nicole
authors.initials: N
authors.lastname: Hamblett
authors.forename: Frank
authors.initials: F
authors.lastname: Accurso
authors.forename: Mark
authors.initials: M
authors.lastname: Dovey
authors.forename: Peter
authors.initials: P
authors.lastname: Hiatt
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.forename: Richard
authors.initials: R
authors.lastname: Moss
authors.forename: George
authors.initials: G
authors.lastname: Retsch-Bogart
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wagener
authors.forename: David
authors.initials: D
authors.lastname: Waltz
authors.forename: Robert
authors.initials: R
authors.lastname: Wilmott
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Zeitlin
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ramsey
mesh_terms: D000280:Administration, Inhalation; D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D001299:Audiometry; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002353:Carrier State / Q000175:diagnosis / Q000188:drug therapy*; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications* / Q000235:genetics; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006311:Hearing Disorders / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis; D008297:Male; D009960:Oropharynx / Q000382:microbiology; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D011550:Pseudomonas aeruginosa; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D012449:Safety; D012720:Severity of Illness Index; D013183:Sputum / Q000382:microbiology; D014031:Tobramycin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D014031:Tobramycin