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Original Research: CYSTIC FIBROSIS |

Efficacy and Safety of Inhaled Aztreonam Lysine for Airway Pseudomonas in Cystic Fibrosis

George Z. Retsch-Bogart, MD; Alexandra L. Quittner, PhD; Ronald L. Gibson, MD, PhD; Christopher M. Oermann, MD; Karen S. McCoy, MD; A. Bruce Montgomery, MD; Peter J. Cooper, MBChB
Author and Funding Information

*From the University of North Carolina at Chapel Hill (Dr. Retsch-Bogart), Chapel Hill, NC; the University of Miami (Dr. Quittner), Coral Gables, FL; Children's Hospital and Regional Medical Center (Dr. Gibson), Seattle, WA; Baylor College of Medicine (Dr. Oermann), Houston, TX; Ohio State University (Dr. McCoy), Columbus, OH; Gilead Sciences, Inc (Dr. Montgomery), Seattle, WA; and The Children's Hospital at Westmead (Dr. Cooper), Sydney, NSW, Australia.

Correspondence to: George Z. Retsch-Bogart, MD, Department of Pediatrics, 5126 Bioinformatics Building, CB No. 7217, 130 Mason Farm Rd, University of North Carolina, Chapel Hill, NC 27599-7217; e-mail: gzrb@med.unc.edu

†A list of participating study sites, site investigators, and study research coordinators for the AIR-CF1 Trial is located in the Appendix.


This study was funded by Gilead Sciences, Inc, and by National Institutes of Health General Clinical Research Center grants M01 RR00188, M01 RR00037, M01 RR02172, M01 RR00043, M01 RR000489, M01 RR00034, M01 RR00039, M01 RR00750, M01 RR01066, M01 RR001070, M01 RR10733, M01 RR00070, M01 RR10710, M01 RR00069, M01 RR00827, M01 RR00082, M01 RR023940, M01 RR00042, M01 RR00400, and M01 RR00065.

Dr. Retsch-Bogart received clinical research support as a site investigator conducting clinical trials from Corus Pharma (purchased by Gilead Sciences, Inc), Gilead Sciences, Inspire Pharmaceuticals, Genentech, Pathogenesis Corp, Boehringer-Ingelheim, and Cystic Fibrosis Foundation Therapeutics, Inc. Dr. Quittner was a consultant and served on an advisory board for Corus Pharma and Gilead Sciences. Dr. Montgomery is employed by Gilead Sciences and prior to this by its predecessor company, Corus Pharma, Inc. He is patent author on Aztreonam Lysine, and Gilead Sciences is patent holder. He holds equity interest in Gilead Sciences. Dr. Gibson received clinical research support as a site investigator conducting clinical trials from Corus Pharma, Gilead Sciences, Inspire Pharmaceuticals, and Cystic Fibrosis Foundation Therapeutics. He served on an advisory board for Genentech. Dr. McCoy received clinical research support as a site investigator conducting clinical trials from Corus Pharma, Gilead Sciences, Inspire Pharmaceuticals, and Genentech. Dr. Oermann received clinical research support as a site investigator conducting clinical trials from Corus Pharma and Gilead Sciences. Dr. Cooper received clinical research support as a site investigator for clinical trials sponsored by Corus Pharma and Gilead Sciences.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(5):1223-1232. doi:10.1378/chest.08-1421
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Background:  We assessed the short-term efficacy and safety of aztreonam lysine for inhalation (AZLI [an aerosolized monobactam antibiotic]) in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA) airway infection.

Methods:  In this randomized, double-blind, placebo-controlled, international study (AIR-CF1 trial; June 2005 to April 2007), patients (n = 164; ≥ 6 years of age) with FEV1 ≥ 25% and ≤ 75% predicted values, and no recent use of antipseudomonal antibiotics or azithromycin were treated with 75 mg of AZLI (three times daily for 28 days) or placebo (1:1 randomization), then were monitored for 14 days after study drug completion. The primary efficacy end point was change in patient-reported respiratory symptoms (CF-Questionnaire-Revised [CFQ-R] Respiratory Scale). Secondary end points included changes in pulmonary function (FEV1), sputum PA density, and nonrespiratory CFQ-R scales. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.

Results:  After 28 days of treatment, AZLI improved the mean CFQ-R respiratory score (9.7 points; p < 0.001), FEV1 (10.3% predicted; p < 0.001), and sputum PA density (− 1.453 log10 cfu/g; p < 0.001), compared with placebo. Significant improvements in Eating, Emotional Functioning, Health Perceptions, Physical Functioning, Role Limitation/School Performance, and Vitality CFQ-R scales were observed. Adverse events were consistent with symptoms of CF lung disease and were comparable for AZLI and placebo except the incidence of “productive cough” was reduced by half in AZLI-treated patients. PA aztreonam susceptibility at baseline and end of therapy were similar.

Conclusions:  In patients with CF, PA airway infection, moderate-to-severe lung disease, and no recent use of antipseudomonal antibiotics or azithromycin, 28-day treatment with AZLI significantly improved respiratory symptoms and pulmonary function, and was well tolerated.

Trial registration:  Clinicaltrials.gov Identifier: NCT00112359

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