Azithromycin in Patients with Cystic Fibrosis Chronically Infected with Pseudomonas aeruginosa: A Randomized Controlled Trial

Context: 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. Design and Setting: 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. Participants: 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 (≥60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center. Intervention: The active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight ≥40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets. Main Outcome Measures: 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 FEV ₁ 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 = .09). Nausea occurred in 17% more participatns 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). Conclusion: 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.