Intermittent Administration of Inhaled Tobramycin in Patients With Cystic Fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group

N Engl J Med. 1999 Jan 7;340(1):23-30. doi: 10.1056/NEJM199901073400104.

Abstract

Background and methods: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on-off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization.

Results: The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001). The patients in the tobramycin group were 26 percent (95 percent confidence interval, 2 to 43 percent) less likely to be hospitalized than those in the placebo group. Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum. The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group, as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group.

Conclusions: In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.

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
  • Adolescent
  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Bronchial Diseases / complications
  • Bronchial Diseases / drug therapy*
  • Bronchial Diseases / microbiology
  • Child
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Hospitalization / statistics & numerical data
  • Humans
  • Infusions, Intravenous
  • Male
  • Nebulizers and Vaporizers
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / isolation & purification
  • Sputum / microbiology
  • Tobramycin / administration & dosage*

Substances

  • Anti-Bacterial Agents
  • Tobramycin