Long term effects of azithromycin in patients with cystic fibrosis: a double-blind, placebo-controlled trial

Annick Clement ¹, Aline Tamalet ¹, Evelyne Le Roux ², Sophie Ravilly ², Brigitte Fauroux ^1* and Jean-Philippe Jais ³

¹ AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, Paris, 75571; Inserm, U719, Paris, France
² Cystic Fibrosis Association Vaincre la Mucoviscidose, France
³ AP-HP, Hôpital Necker, Biostatistic Department, Paris, 75753, France

^* To whom correspondence should be addressed. E-mail: brigitte.fauroux{at}trs.aphp.fr.

Accepted 31 May 2006

Abstract

Background: Macrolides display immuno-modulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis.

Methods: A multi-centre, randomised, double blind placebo-controlled trial was conducted from October 2001 to June 2003. The criteria for enrolment were age older than 6 yrs, and forced expiratory volume in 1 second of 40% or more. The active group received either 250 mg or 500 mg (bodyweight < or > 40 kg) of oral azithromycin, 3 times a week for 12 months. The primary endpoint was change in forced expiratory volume in 1 second.

Results: Eighty two patients (mean age: 11.0 yrs [3.3]; mean % predicted forced expiratory volume in 1 second: 85% [22%]) were randomised, 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in forced expiratory volume in 1 second at month 12 was not significantly different between the 2 groups. The number of pulmonary exacerbations (count ratio: 0.50 [0.32; 0.79], p<0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio: 0.37 [0.22; 0.63], p<0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio: 0.55 [0.36; 0.85] p<0.01). No severe adverse events were reported.

Conclusion: Long term use of low-dose azithromycin in young patients with cystic fibrosis demonstrates a beneficial effect on lung disease expression, even prior to colonisation with Pseudomonas aeruginosa.

Keywords: antibiotic treatment, children, lung, lung function, respiratory exacerbation

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