Macrolide antibiotics for cystic fibrosis

Abstract

Background: The antibiotic treatment of chest infections which characterise cystic fibrosis (CF) has significantly improved prospects for people with CF. The nature of organisms causing these infections has restricted antibiotic choice. Pseudomonas aeruginosa, especially, is resistant to most oral antibiotics. There is evidence from the laboratory and from other disease processes that macrolide antibiotics, whilst not directly active against Pseudomonas aeruginosa, may have indirect actions against this organism.

Objectives: We aimed to test the hypotheses that macrolide antibiotics:(1) improve clinical status compared to placebo or another antibiotic;(2) have no unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.

Search strategy: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture macrolide antibiotics for unpublished or follow-up data (December 2002). Date of the most recent search of the Group's register: March 2003.

Selection criteria: Published or unpublished randomised controlled trials of macrolide antibiotics compared to placebo, another class of antibiotic or another macrolide antibiotic. Studies comparing regimens of the same macrolide antibiotic at different doses will also be included.

Data collection and analysis: Two reviewers independently extracted data and assessed study quality. Two groups were contacted for missing data, but these were unavailable for the review.

Main results: Searches identified eleven studies, two were included in this review (101 participants). One study enrolled adults and the other children (a significant number of whom were not colonised with Pseudomonas aeruginosa). Both studies report small but significant changes in respiratory function (% change in FEV1) in favour of azithromycin. Meta-analysis at the two-month time point demonstrated a significant benefit with respect to percentage change in FVC (weighted mean difference 5.42 (1.77 to 9.07)) from azithromycin, but no difference with respect to percentage change of FEV1. There were no significant adverse effects reported.

Reviewer's conclusions: The role of macrolides in the management of CF lung disease remains unclear and there are many unanswered questions. Two small randomised controlled trials have suggested short-term improvement in respiratory function with azithromycin. Until the results of further studies are available the widespread use of azithromycin in CF cannot be advocated and should be restricted to well-designed randomised controlled trials.