Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis.
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; >or= 6 years of age) with FEV(1) >or= 25% and <or= 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 (FEV(1)), 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), FEV(1) (10.3% predicted; p < 0.001), and sputum PA density (- 1.453 log(10) 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.


BACKGROUND
Clinicaltrials.gov Identifier: NCT00112359.
Retsch-Bogart
George Z
GZ
University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: gzrb@med.unc.edu.
Quittner
Alexandra L
AL
University of Miami, Coral Gables, FL.
Gibson
Ronald L
RL
Children's Hospital and Regional Medical Center, Seattle, WA.
Oermann
Christopher M
CM
Baylor College of Medicine, Houston, TX.
McCoy
Karen S
KS
Ohio State University, Columbus, OH.
Montgomery
A Bruce
AB
Gilead Sciences, Inc, Seattle, WA.
Cooper
Peter J
PJ
The Children's Hospital at Westmead, Sydney, NSW, Australia.
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001398:Aztreonam / Q000008:administration & dosage*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D001398:Aztreonam