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Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.

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.

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  • Authors+Show Affiliations

    ,

    Department of Pediatrics, University of Washington School of Medicine, Seattle, USA.

    , , , , , , , , , ,

    Source

    The New England journal of medicine 340:1 1999 Jan 07 pg 23-30

    MeSH

    Administration, Inhalation
    Adolescent
    Adult
    Anti-Bacterial Agents
    Bronchial Diseases
    Child
    Cystic Fibrosis
    Double-Blind Method
    Female
    Forced Expiratory Volume
    Hospitalization
    Humans
    Infusions, Intravenous
    Male
    Nebulizers and Vaporizers
    Pseudomonas Infections
    Pseudomonas aeruginosa
    Sputum
    Tobramycin

    Pub Type(s)

    Clinical Trial
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    9878641

    Citation

    Ramsey, B W., et al. "Intermittent Administration of Inhaled Tobramycin in Patients With Cystic Fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group." The New England Journal of Medicine, vol. 340, no. 1, 1999, pp. 23-30.
    Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med. 1999;340(1):23-30.
    Ramsey, B. W., Pepe, M. S., Quan, J. M., Otto, K. L., Montgomery, A. B., Williams-Warren, J., ... Smith, A. L. (1999). Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. The New England Journal of Medicine, 340(1), pp. 23-30.
    Ramsey BW, et al. 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. PubMed PMID: 9878641.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. AU - Ramsey,B W, AU - Pepe,M S, AU - Quan,J M, AU - Otto,K L, AU - Montgomery,A B, AU - Williams-Warren,J, AU - Vasiljev-K,M, AU - Borowitz,D, AU - Bowman,C M, AU - Marshall,B C, AU - Marshall,S, AU - Smith,A L, PY - 1999/1/8/pubmed PY - 1999/1/8/medline PY - 1999/1/8/entrez SP - 23 EP - 30 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 340 IS - 1 N2 - 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. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/9878641/full_citation L2 - https://www.nejm.org/doi/10.1056/NEJM199901073400104?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -