title: Long term azithromycin therapy in cystic fibrosis patients: a study on drug levels and sputum properties.
abstract: BACKGROUND
  Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro.
  
  
  OBJECTIVE
  Drug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo.
  
  
  METHODS
  In an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology.
  
  
  RESULTS
  AZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 microg/mL (0.6 to 79.3 microg/mL, interquartiles 1.4 to 33.4 microg/mL) and 0.5 microg/mL (range less than 0.1 [below detection level] to 5.2 microg/mL, interquartiles 0.2 to 1.4 microg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one.
  
  
  CONCLUSIONS
  The findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.
authors.affiliation: Department of Pediatric Pulmonology and Neonatology, Hanover Medical School, Hanover, Germany. baumann.ulrich@mh-hannover.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Malcolm
authors.initials: M
authors.lastname: King
authors.forename: Ernst M
authors.initials: EM
authors.lastname: App
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tai
authors.forename: Armin
authors.initials: A
authors.lastname: König
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Fischer
authors.forename: Torsten
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sextro
authors.forename: Horst
authors.initials: H
authors.lastname: von der Hardt
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011550:Pseudomonas aeruginosa; D012463:Saliva / Q000737:chemistry; D013183:Sputum / Q000737:chemistry / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin