Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial.
BACKGROUND
Treatment strategies for cystic fibrosis (CF) lung disease include antibiotics, mucolytics, and anti-inflammatory therapies. Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF.


OBJECTIVE
To determine if an association between azithromycin use and pulmonary function exists in patients with CF.


METHODS
A multicenter, randomized, double-blind, placebo-controlled trial conducted from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United States.


METHODS
Of the 251 screened participants with a diagnosis of CF, 185 (74%) were randomized. Eligibility criteria included age 6 years or older, infection with Pseudomonas aeruginosa for 1 or more years, and a forced expiratory volume in 1 second (FEV1) of 30% or more. Participants were stratified by FEV1 (> or =60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center.


METHODS
The active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight > or =40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets.


METHODS
Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain.


RESULTS
The azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV1 at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P =.009). Nausea occurred in 17% more participants in the azithromycin group (P =.01), diarrhea in 15% more (P =.009), and wheezing in 13% more (P =.007). Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P =.03) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P =.02).


CONCLUSIONS
Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005540:Forced Expiratory Flow Rates; D006760:Hospitalization; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D010196:Pancreatic Elastase / Q000097:blood; D016016:Proportional Hazards Models; D011552:Pseudomonas Infections / Q000150:complications* / Q000188:drug therapy*; D011788:Quality of Life; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D017963:Azithromycin; D010196:Pancreatic Elastase