Azithromycin in cystic fibrosis

To the Editors:

We have read with interest the article by Southern and Barker 1. The authors critically reviewed the evidence from the randomised, controlled trials of the role of azithromycin in the management of cystic fibrosis (CF). In the three randomised, controlled studies described, the effects of up to 6 months of therapy with azithromycin in CF have been reported 2–4. However, the controlled setting of randomised trials may differ from the clinical practice. Therefore, we can understand the authors' cautious closing remark on the precise role of azithromycin in the clinical setting.

We have recently audited our use of long-term azithromycin therapy in adult patients attending the Regional Adult CF unit, Leeds, UK 5. A total of 36 patients (17 female), all of whom were colonised with Pseudomonas aeruginosa, had 500 mg of azithromycin 3 times·week⁻¹ for a mean±sd period of 9±6 months. Mean age, Northern chest radiograph score, Shwachman-Kulczycki score and forced expiratory volume in one second (FEV₁) were 24±7 yrs, 12±3, 68±14, and 1.9±0.9 L, respectively. In the group as a whole, there was no overall change in lung function during the treatment period. However, we were able to identify a subgroup of 24 patients in whom therapy with azithromycin was associated with a mean±sd increase in FEV₁ by 0.3±0.2 L. This group had significantly lower levels of antibodies to P. aeruginosa (p = 0.007), with a median (range) of 19 (4–136) versus 40 (5–325) U·mL⁻¹, and a lower number of exacerbations requiring i.v. antibiotics in the 12 months prior to starting azithromycin (3 (1–6) versus 5 (2–7); p = 0.01) when compared to those patients where lung function remained unchanged.

We believe that our findings provide additional information on the clinical use of azithromycin. First, not all patients colonised with P. aeruginosa improve with azithromycin therapy. Secondly, the CF patients in whom treatment with azithromycin is more likely to be associated with improvements in lung function are characterised by a lower immunological response to P. aeruginosa and a lower frequency of exacerbations.

Our data suggest that therapy with azithromycin should be considered earlier in the disease process. Further data on whether therapy should be introduced before colonisation with Pseudomonas aeruginosa occurs is required.