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Significant Microbiological Effect of Inhaled Tobramycin in Young Children with Cystic Fibrosis

Department of Pediatrics, Children's Hospital and Regional Medical Center/University of Washington, Seattle, Washington; Department of Pediatrics, University of Colorado, Denver, Colorado; Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Department of Pediatrics, Stanford University, Palo Alto, California; Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio; Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina; Department of Pediatrics, Harvard University, Boston, Massachusetts; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland; and Cystic Fibrosis Therapeutics Development Network, Cystic Fibrosis Foundation/University of Washington, Seattle, Washington

Correspondence and requests for reprints should be addressed to Ronald L. Gibson, M.D., Children's Hospital and Regional Medical Center, 4800 Sandpoint Way NE, Mail Stop 3D-4, P.O. Box 5371, Seattle, WA 98105-0371. E-mail: ron.gibson{at}seattlechildrens.org

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.

Key Words: bronchoalveolar lavage • lung • Pseudomonas

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