Azithromycin in Patients With Cystic Fibrosis Chronically Infected With Pseudomonas aeruginosa

TLDR

Cystic fibrosis lung disease is treated with antibiotics, mucolytics, and anti‑inflammatory agents, and emerging evidence indicates macrolide antibiotics may offer additional benefit. The study aimed to assess whether azithromycin use is associated with improved pulmonary function in cystic fibrosis patients. In a multicenter, randomized, double‑blind, placebo‑controlled trial, 185 CF patients aged ≥6 years with chronic Pseudomonas aeruginosa infection and FEV1 ≥30% were randomized to azithromycin 3 days/week for 168 days or placebo, with primary outcome FEV1 change and secondary outcomes exacerbations and weight gain. Azithromycin produced a statistically significant 0.094‑L improvement in FEV1, reduced exacerbation risk (HR 0.65), and increased weight by 0.7 kg, but was associated with higher rates of nausea, diarrhea, and wheezing.

Abstract

ContextTreatment 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.ObjectiveTo determine if an association between azithromycin use and pulmonary function exists in patients with CF.Design and SettingA 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.ParticipantsOf 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.InterventionThe 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 MeasuresChange in FEV1 from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain.ResultsThe 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 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).ConclusionAzithromycin 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.