Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis

Abstract

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.

Trial registration: Clinicaltrials.gov Identifier: NCT00112359.

Figures

Figure 1

Study design and patient disposition.

Figure 2

Left: adjusted mean CFQ-R-respiratory scores, FEV1, and sputum PA density; change from baseline to study end (days 0 to 42). Child, teen, and adult responses were combined for CFQ-R-Respiratory scores. Right: change from baseline to end of treatment for CFQ-R-Respiratory scores and FEV1; effects of age and baseline CF lung disease severity. Note that the mean change from baseline values improved for all groups treated with AZLI and worsened for all groups treated with placebo. For all patients: AZLI group, n = 80; placebo group, n = 83/84; for disease severity-moderate: AZLI group, n = 50; placebo group, n = 53/54; for disease severity-severe: AZLI group, n = 30; placebo group, n = 30; for patient age < 18 years: AZLI group, n = 21; placebo group, n = 16; for patient age ≥ 18 years: AZLI group, n = 59; placebo group, n = 67/68.