title: Continuous alternating inhaled antibiotics for chronic pseudomonal infection in cystic fibrosis.
abstract: Inhaled antibiotics are standard of care for treating chronic pseudomonal respiratory infections in cystic fibrosis patients, initially approved for intermittent administration. However, use of continuous inhaled antibiotic regimens of differing combinations is growing.
  
  
  
  This double-blind trial compared continuous alternating therapy (CAT) to an intermittent treatment regimen. Subjects were treated with 3cycles of 28-days inhaled aztreonam (AZLI) or placebo 3-times daily alternating with 28-days open-label tobramycin inhalation solution (TIS).
  
  
  
  90 subjects were randomized over 18months. Study enrollment was limited, in part because of evolving practices by clinicians of adopting a CAT regimen in clinical practice; consequently the study was underpowered. AZLI/TIS treatment reduced exacerbation rates by 25.7% (p=0.25; primary endpoint) and rates of respiratory hospitalizations by 35.8% compared with placebo/TIS (p=0.14). AZLI/TIS CAT therapy was well tolerated.
  
  
  
  This trial illustrates challenges with studying treatment regimens in a constantly evolving CF care environment. Nonetheless, the results of this trial indicate that AZLI/TIS CAT is well tolerated and may provide additional clinical benefit in CF patients compared with intermittent use of TIS alone. Clinicaltrials.gov: NCT01641822.
authors.affiliation: Medical University of South Carolina, 96 Jonathan Lucas Street, 812-CSB, Charleston, SC 29425, USA. Electronic address: flumepa@musc.edu.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Flume
authors.affiliation: Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA. Electronic address: John.clancy@cchmc.org.
authors.forename: John P
authors.initials: JP
authors.lastname: Clancy
authors.affiliation: University of North Carolina at Chapel Hill, Division of Pediatric Pulmonology, 450 MacNider Hall, CB#7217, 333 S. Columbia St., Chapel Hill, NC 27599-7217, USA. Electronic address: gzrb@med.unc.edu.
authors.forename: George Z
authors.initials: GZ
authors.lastname: Retsch-Bogart
authors.affiliation: University of Toronto, Division of Respirology, St Michael's Hospital 6-049, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Electronic address: TULLISE@smh.ca.
authors.forename: D Elizabeth
authors.initials: DE
authors.lastname: Tullis
authors.affiliation: Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA. Electronic address: mark.bresnik@gilead.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Bresnik
authors.affiliation: Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA. Electronic address: alex.derchak@gilead.com.
authors.forename: P Alex
authors.initials: PA
authors.lastname: Derchak
authors.affiliation: Gilead Sciences, 199 E. Blaine St., Seattle, WA 98102, USA. Electronic address: sandy.lewis@gilead.com.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Lewis
authors.affiliation: University of Washington, Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA 98105, USA. Electronic address: bonnie.ramsey@seattlechildrens.org.
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001398:Aztreonam / Q000008:administration & dosage*; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D054539:Medication Therapy Management; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001398:Aztreonam; D014031:Tobramycin
keywords: Aerosol; Antibiotics; Cystic fibrosis; Pseudomonas; Pulmonary exacerbation