This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200712-1804OCv1 178/9/921    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by McCoy, K. S. Articles by Montgomery, A. B. PubMed PubMed Citation Articles by McCoy, K. S. Articles by Montgomery, A. B.

Inhaled Aztreonam Lysine for Chronic Airway Pseudomonas aeruginosa in Cystic Fibrosis

¹ Ohio State University, Columbus, Ohio; ² University of Miami, Coral Gables, Florida; ³ Baylor College of Medicine, Houston, Texas; ⁴ Children's Hospital and Regional Medical Center, Seattle, Washington; ⁵ University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and ⁶ Gilead Sciences, Inc., Seattle, Washington

Correspondence and requests for reprints should be addressed to Karen S. McCoy, M.D., Associate Professor of Pediatrics, Ohio State University, Nationwide Children's Hospital, Columbus, OH 43205. E-mail: karen.mccoy{at}nationwidechildrens.org

Rationale: The effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study.

Objectives: To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF.

Methods: After randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; 6 yr; 3 TIS courses within previous year; FEV₁ 25% and 75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV₁), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.

Measurements and Main Results: AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV₁ (6.3%, P = 0.001), and sputum PA density (–0.66 log₁₀ cfu/g, P = 0.006) compared with placebo; no AZLI dose–response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar.

Conclusions: AZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated.

Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).

Key Words: cystic fibrosis • Pseudomonas • aztreonam • inhaled antibiotics • patient-reported outcomes • respiratory symptoms

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Cystic fibrosis is a chronic disease often involving endobronchial infection with Pseudomonas aeruginosa, which is difficult to treat. What This Study Adds to the Field Safety and efficacy data on inhaled aztreonam show that this new formulation may be an alternative treatment option for patients with cystic fibrosis and chronic P. aeruginosa infection.