title: Macrolide antibiotics for cystic fibrosis.
abstract: BACKGROUND
  Chronic severe infection with Pseudomonas aeruginosa, affects many people with cystic fibrosis (CF). 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.
  
  
  OBJECTIVE
  We aimed to test the hypotheses that, in people with CF, macrolide antibiotics:(1) improve clinical status compared to placebo or another antibiotic;(2) do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.
  
  
  METHODS
  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known to work in the field, previous authors and pharmaceutical companies who manufacture macrolide antibiotics for unpublished or follow-up data (December 2003). Most recent search of the Group's register: January 2004
  
  
  METHODS
  Published or unpublished randomised controlled trials of macrolide antibiotics compared to placebo, another class of antibiotic or another macrolide antibiotic.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.
  
  
  METHODS
  Two reviewers independently extracted data and assessed study quality. Three groups were contacted for missing data and we hope to include these in future reviews.
  
  
  RESULTS
  Searches identified 14 studies, four were included in this review (296 participants). Two studies enrolled adults, one children (a significant number of whom were not colonised with Pseudomonas aeruginosa) and one both adults and children. All the clinical studies reported small but significant improvements in respiratory function with azithromycin versus placebo. Meta-analysis at the one-month and six-month time points demonstrates a significant benefit with respect to relative change in FEV1 (at six months, for n = 104, azithromycin and n = 114, placebo; WMD 5.82% (95% CI 2.45 to 9.20)). The largest study reported a significant increase in mild adverse events (nausea, diarrhoea and wheezing).
  
  
  CONCLUSIONS
  There is clear evidence from these studies of a small but significant improvement in respiratory function following treatment with azithromycin. The largest study employed a three times a week dose and, in this study, treatment with azithromycin was associated with a significant increase in mild adverse events. Further studies are needed to clarify the precise role of azithromycin in the treatment of CF lung disease.
authors.affiliation: Child Health, University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool, Merseyside, UK, L12 2AP.
authors.forename: K W
authors.initials: KW
authors.lastname: Southern
authors.forename: P M
authors.initials: PM
authors.lastname: Barker
authors.forename: A
authors.initials: A
authors.lastname: Solis
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications*; D006801:Humans; D018942:Macrolides; D017063:Outcome Assessment, Health Care; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D016032:Randomized Controlled Trials as Topic
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides