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

Abstract

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.

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

“…Aztreonam has been used via the parenteral route to treat infections caused by aerobic gramnegative bacteria, including Pa, and was reformulated as a lysine salt for inhalation delivery [105]. Randomized, double-blind placebo controlled trials [108][109][110][111][112] and open label studies [113,114] investigated the safety profile of AZLI (Supplementary Tables 5). Bronchial hyperreactivity, defined as a decrease of > 15% in FEV1, was observed in four short-term trials (28 days) with prevalence ranging from 2-8% [108][109][110][111]. Retsch-Bogart et al found that after one week of therapy, BHR following AZLI inhalation was not different among groups [109].…”

Pulmonary drug delivery systems for antimicrobial agents: facts and myths

“…On the other hand, the FDA requested the performance of another clinical trial [54]. In the ongoing clinical trials, eFlow is used as the delivery device [55]. Consequently, if the medicine is finally approved by the FDA, eFlow will be the recommended device.…”

Lung Transplantation for Cystic Fibrosis

“…This guidance outlines a set of rigorous requirements for instruments used to assess the efficacy of new treatments and interventions while also encouraging their use as a means of representing the patient's perception of benefit (101,(113)(114)(115)(116)(117). It is critically important to answer the question about the extent to which lung transplantation for CF provides a significant HRQoL benefit (118).…”

“…It is critically important to answer the question about the extent to which lung transplantation for CF provides a significant HRQoL benefit (118). There is now a reliable, valid, and widely used HRQoL measure for CF, the CFQ-R,which has demonstrated responsivity across a variety of clinical trials (114,116,118). The Cystic Fibrosis Foundation recently funded a longitudinal study using the CFQ-R in pediatric patients receiving lung transplants, yielding some promising results (119,120).…”