title: Fosfomycin/tobramycin for inhalation in patients with cystic fibrosis with pseudomonas airway infection.
abstract: BACKGROUND
  Fosfomycin/tobramycin for inhalation (FTI), a unique, broad-spectrum antibiotic combination, may have therapeutic potential for patients with cystic fibrosis (CF).
  
  
  OBJECTIVE
  To evaluate safety and efficacy of FTI (160/40 mg or 80/20 mg), administered twice daily for 28 days versus placebo, in patients greater than or equal to 18 years of age, with CF, chronic Pseudomonas aeruginosa (PA) airway infection, and FEV(1) greater than or equal to 25% and less than or equal to 75% predicted.
  
  
  METHODS
  This double-blind, placebo-controlled, multicenter study assessed whether FTI/placebo maintained FEV(1) % predicted improvements achieved following a 28-day, open-label, run-in course of aztreonam for inhalation solution (AZLI).
  
  
  RESULTS
  A total of 119 patients were randomized to FTI (160/40 mg: n = 41; 80/20 mg: n = 38) or placebo (n = 40). Mean age was 32 years and mean FEV(1) was 49% predicted at screening. Relative improvements in FEV(1) % predicted achieved by the AZLI run-in were maintained in FTI groups compared with placebo (160/40 mg vs. placebo: 6.2% treatment difference favoring FTI, P = 0.002 [primary endpoint]; 80/20 mg vs. placebo: 7.5% treatment difference favoring FTI, P < 0.001). The treatment effect on mean PA sputum density was statistically significant for the FTI 80/20 mg group versus placebo (-1.04 log(10) PA colony-forming units/g sputum difference, favoring FTI; P = 0.01). Adverse events, primarily cough, were consistent with CF disease. Respiratory events, including dyspnea and wheezing, were less common with FTI 80/20 mg than FTI 160/40 mg. No clinically significant differences between groups were reported for laboratory values.
  
  
  CONCLUSIONS
  FTI maintained the substantial improvements in FEV(1) % predicted achieved during the AZLI run-in and was well tolerated. FTI is a promising antipseudomonal therapy for patients with CF.
authors.affiliation: Cincinnati Children's Hospital Medical Center, OH 45229, USA. bruce.trapnell@cchmc.org
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Trapnell
authors.forename: Susanna A
authors.initials: SA
authors.lastname: McColley
authors.forename: Dana G
authors.initials: DG
authors.lastname: Kissner
authors.forename: Mark W
authors.initials: MW
authors.lastname: Rolfe
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rosen
authors.forename: Matthew
authors.initials: M
authors.lastname: McKevitt
authors.forename: Lisa
authors.initials: L
authors.lastname: Moorehead
authors.forename: A Bruce
authors.initials: AB
authors.lastname: Montgomery
authors.forename: David E
authors.initials: DE
authors.lastname: Geller
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003371:Cough / Q000139:chemically induced; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005578:Fosfomycin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012129:Respiratory Function Tests; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D005578:Fosfomycin; D014031:Tobramycin
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