Long term azithromycin therapy in cystic fibrosis patients: a study on drug levels and sputum properties.
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.
Baumann
Ulrich
U
Department of Pediatric Pulmonology and Neonatology, Hanover Medical School, Hanover, Germany. baumann.ulrich@mh-hannover.de
King
Malcolm
M
App
Ernst M
EM
Tai
Shusheng
S
König
Armin
A
Fischer
Julia J
JJ
Zimmermann
Torsten
T
Sextro
Wolfgang
W
von der Hardt
Horst
H
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
D000900:Anti-Bacterial Agents; D017963:Azithromycin