Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection.
BACKGROUND
Data on the effects of long-term treatment with azithromycin (AZM) on inflammatory markers in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa are scarce. So far there is no pharmacokinetic and clinical data on once-weekly dosage of AZM in CF patients.


METHODS
In a randomised double-blind, placebo-controlled trial, patients received AZM or placebo 1 per week for 8 weeks (AZM dosage--20-29 kg: 500 mg, 30-39 kg: 750 mg, 40-49 kg: 1000 mg and > or = 50 kg: 1250 mg) after a course of intravenous antipseudomonal antibiotics. Pulmonary function tests, the serum markers LPS-binding protein (LBP), interleukin-8 (IL-8), CRP, P. aeruginosa alginate in sputum samples and quality of life scores were evaluated.


RESULTS
Thirty-eight patients (21 AZM/17 placebo) (mean age: 23.7 years; mean FEV(1): 62% of predicted) were recruited. After treatment (mean dose of 21.2 mg/kg body weight once a week) pulmonary function declined in both groups compared to baseline (i.e. after cessation of i.v. antibiotics). The AZM group was significantly better for mean changes in serum CRP (AZM: +0.9 mg/l, placebo: +21.6 mg/l, p=0.019), lipopolysaccharide binding protein in serum, LBP (AZM: +0.9 microg/ml, placebo: +7.0 microg/ml, p=0.015), serum interleukin-8 (AZM: -3.1 pg/ml, placebo: +2.9 pg/ml, p=0.001) and alginate in sputum (AZM: +85 microg/ml, placebo: +353 microg/ml, p=0.048). Quality of life was significantly better after AZM and there was no increase in treatment-related adverse events.


CONCLUSIONS
Once-weekly azithromycin ameliorated inflammatory reactions and improved quality of life. A decline of pulmonary function after cessation of i.v. antibiotics could not be prevented.
Steinkamp
Gratiana
G
CF-Centre Hamburg-Altona and Clinical Research Hannover, Germany. steinkamp@med-wiss.com
Schmitt-Grohe
Sabina
S
Döring
Gerd
G
Staab
Doris
D
Pfründer
Dietmar
D
Beck
Gudrun
G
Schubert
Ralf
R
Zielen
Stefan
S
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017963:Azithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism; D011550:Pseudomonas aeruginosa; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017963:Azithromycin