D Elizabeth Tullis1, Jane L Burns2, George Z Retsch-Bogart3, Mark Bresnik4, Noreen R Henig4, Sandra A Lewis5, John J Lipuma6. 1. Department of Medicine, University of Toronto, Keenan Research Centre of Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada. Electronic address: tullise@smh.ca. 2. University of Washington, Seattle Children's Research Institute, 1900 Ninth Avenue C9S8, Seattle, WA 98101, USA. 3. University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. 4. Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA. 5. Gilead Sciences, 199 E. Blaine St., Seattle, WA 98102, USA. 6. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
BACKGROUND: Individuals with Burkholderia spp. infection have historically been excluded from efficacy trials of inhaled antibiotics, including aztreonam for inhalation solution (AZLI). METHODS: A double-blind, placebo-controlled, 24-week trial of continuous AZLI/placebo treatment was undertaken in individuals with cystic fibrosis (CF) and chronic Burkholderia spp. infection. All subjects also received usual medical care (determined by their physicians). Additional antibiotic use was not restricted. RESULTS: Baseline FEV1% predicted values ranged from 15.8% to 114.6%. No significant treatment differences (AZLI vs. placebo) were observed at week 24 for any endpoints, including FEV1% predicted, number of respiratory exacerbations requiring systemic/inhaled antibiotics, or hospitalizations. Continuous AZLI administration was well tolerated. Burkholderia spp. susceptibility to antibiotics commonly used in CF therapy showed little change. CONCLUSIONS: 24-weeks of continuous AZLI treatment did not significantly improve lung function in CF subjects with chronic Burkholderia spp. infection. Non-study antibiotic use may have confounded any potential AZLI effects.
RCT Entities:
BACKGROUND: Individuals with Burkholderia spp. infection have historically been excluded from efficacy trials of inhaled antibiotics, including aztreonam for inhalation solution (AZLI). METHODS: A double-blind, placebo-controlled, 24-week trial of continuous AZLI/placebo treatment was undertaken in individuals with cystic fibrosis (CF) and chronic Burkholderia spp. infection. All subjects also received usual medical care (determined by their physicians). Additional antibiotic use was not restricted. RESULTS: Baseline FEV1% predicted values ranged from 15.8% to 114.6%. No significant treatment differences (AZLI vs. placebo) were observed at week 24 for any endpoints, including FEV1% predicted, number of respiratory exacerbations requiring systemic/inhaled antibiotics, or hospitalizations. Continuous AZLI administration was well tolerated. Burkholderia spp. susceptibility to antibiotics commonly used in CF therapy showed little change. CONCLUSIONS: 24-weeks of continuous AZLI treatment did not significantly improve lung function in CF subjects with chronic Burkholderia spp. infection. Non-study antibiotic use may have confounded any potential AZLI effects.
Authors: Felix Ratjen; Scott C Bell; Steven M Rowe; Christopher H Goss; Alexandra L Quittner; Andrew Bush Journal: Nat Rev Dis Primers Date: 2015-05-14 Impact factor: 52.329
Authors: James F Chmiel; Timothy R Aksamit; Sanjay H Chotirmall; Elliott C Dasenbrook; J Stuart Elborn; John J LiPuma; Sarath C Ranganathan; Valerie J Waters; Felix A Ratjen Journal: Ann Am Thorac Soc Date: 2014-09