Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis.
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.
Gibson
Ronald L
RL
Department of Pediatrics, Children's Hospital and Regional Medical Center/University of Washington, Seattle, Washington 98105-0371, USA. ron.gibson@seattlechildrens.org
Emerson
Julia
J
McNamara
Sharon
S
Burns
Jane L
JL
Rosenfeld
Margaret
M
Yunker
Ann
A
Hamblett
Nicole
N
Accurso
Frank
F
Dovey
Mark
M
Hiatt
Peter
P
Konstan
Michael W
MW
Moss
Richard
R
Retsch-Bogart
George
G
Wagener
Jeffrey
J
Waltz
David
D
Wilmott
Robert
R
Zeitlin
Pamela L
PL
Ramsey
Bonnie
B
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
D000900:Anti-Bacterial Agents; D003404:Creatinine; D014031:Tobramycin