title: Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa.
abstract: BACKGROUND
  Lower respiratory tract infection with Pseudomonas aeruginosa (PA) is associated with increased morbidity in patients with cystic fibrosis (CF). Current treatment guidelines for inhaled antibiotics are not universally followed due to the perception of decreased efficacy, increasing resistance, drug intolerance, and high treatment burden with current aerosol antibiotics. New treatment options for CF pulmonary infections are needed.
  
  
  OBJECTIVE
  This study assessed the efficacy and safety of a novel aerosol formulation of levofloxacin (MP-376, Aeroquin) in a heavily treated CF population with PA infection.
  
  
  METHODS
  This study randomized 151 patients with CF with chronic PA infection to one of three doses of MP-376 (120 mg every day, 240 mg every day, 240 mg twice a day) or placebo for 28 days. The primary efficacy endpoint was the change in sputum PA density. Secondary endpoints included changes in pulmonary function, the need for other anti-PA antimicrobials, changes in patient-reported symptom scores, and safety monitoring.
  
  
  RESULTS
  All doses of MP-376 resulted in reduced sputum PA density at Day 28, with MP-376 240 mg twice a day showing a 0.96 log difference compared with placebo (P = 0.001). There was a dose-dependent increase in FEV(1) for MP-376, with a difference of 8.7% in FEV(1) between the 240 mg twice a day group and placebo (P = 0.003). Significant reductions (61-79%) in the need for other anti-PA antimicrobials were observed with all MP-376 treatment groups compared with placebo. MP-376 was generally well tolerated relative to placebo.
  
  
  CONCLUSIONS
  Nebulized MP-376was well tolerated and demonstrated significant clinical efficacy in heavily treated patients with CF with PA lung infection. Clinical trial registered with www.clinicaltrials.gov (NCT00677365).
authors.affiliation: Nemours Children's Clinic, Orlando, FL 32801, USA. dgeller@nemours.org
authors.forename: David E
authors.initials: DE
authors.lastname: Geller
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Flume
authors.forename: Doris
authors.initials: D
authors.lastname: Staab
authors.forename: Rainald
authors.initials: R
authors.lastname: Fischer
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Loutit
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Conrad
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003550:Cystic Fibrosis / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D064704:Levofloxacin; D015242:Ofloxacin / Q000008:administration & dosage*; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012129:Respiratory Function Tests; D012996:Solutions; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D012996:Solutions; D064704:Levofloxacin; D015242:Ofloxacin