Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial.
BACKGROUND
The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial.


METHODS
41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat.


RESULTS
Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects.


CONCLUSIONS
A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.
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Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK.
Balfour-Lynn
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Bush
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Rosenthal
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D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D017963:Azithromycin / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005080:Exercise Test; D005541:Forced Expiratory Volume; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D019272:Leukocyte Elastase / Q000032:analysis; D010865:Pilot Projects; D011788:Quality of Life; D013183:Sputum / Q000737:chemistry
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D017963:Azithromycin; D019272:Leukocyte Elastase