Long-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis.
OBJECTIVE
To determine the effect of long-term suppression of Pseudomonas aeruginosa on lung function and other clinical end points in adolescent patients with cystic fibrosis (CF).


METHODS
Two identical, randomized, placebo-controlled trials followed by three open-label follow-on trials.


METHODS
Sixty-nine CF study centers in the United States.


METHODS
Active drug consisting of a 300-mg tobramycin solution for inhalation (TSI).


METHODS
One hundred twenty-eight adolescent CF patients (aged 13 to 17 years) with P aeruginosa and mild-to-moderate lung disease (FEV(1) percent predicted > or = 25% and < or = 75%).


METHODS
Pulmonary function, P aeruginosa colony forming unit density, incidence of hospitalization and IV antibiotic use, weight gain, and aminoglycoside toxicity were monitored.


RESULTS
At the end of the first three 28-day cycles of TSI treatment, patients originally randomized to TSI and placebo treatments exhibited improvements in FEV(1) percent predicted of 13.5% and 9.4%, respectively. FEV(1) percent predicted was maintained above the value at initiation of TSI treatment in both groups. At the end of the last "on-drug" period (92 weeks), patients originally randomized to TSI and placebo treatments showed improvements of 14.3% and 1.8%, respectively. Improvement in pulmonary function was significantly correlated with reduction in P aeruginosa colony forming unit density (p = 0.0001). The average number of hospitalizations and IV antibiotic courses did not increase over time. TSI treatment was associated with increased weight gain and body mass index. P aeruginosa susceptibility to tobramycin decreased slightly over time, but this was not correlated with clinical response.


CONCLUSIONS
TSI treatment improved pulmonary function and weight gain in adolescent patients with CF over a 2-year period of long-term, intermittent use.
Moss
Richard B
RB
Department of Pediatrics, Stanford University Medical Center, Palo Alto, CA 94304-5786, USA. rmoss@stanford.edu
D000280:Administration, Inhalation; D000293:Adolescent; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008134:Long-Term Care; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects
D014031:Tobramycin