A study published in the Journal of the American Medical Association [2010;303(17):1707-1715] has reported that a 24-week regimen of azithromycin therapy in children and adolescents with cystic fibrosis (CF) who were not infected with Pseudomonas aeruginosa did not result in improved pulmonary function, but did reduce pulmonary exacerbations and improve weight gain.
The multicenter, randomized, double-blind, placebo-controlled trial enrolled 260 patients and was conducted from February 2007 to July 2009. Previous studies had reported reduced pulmonary exacerbations, increased weight gain, or improved lung function with azithromycin, mainly among those with chronic P aeruginosa infection. With this in mind, the goal of the reported study was to determine if azithromycin therapy improved lung function, reduced pulmonary exacerbations, and was safe and well tolerated in the population of CF patients studied.
The study included CF patients who were between the ages of 6 and 18 years; had a weight of at least 18 kg; had a forced expiratory volume at 1 second (FEV1) of at least 50% predicted; and ≥2 negative cultures of P aeruginosa obtained at least 1 year prior to randomization (could include a negative screening culture 7-14 days prior to randomization).
Participants were randomized to receive 250 mg of azithromycin (for those weighing 18.0-35.9 kg), 500 mg of azithromycin (for those weighing ≥36 kg), or placebo 3 times per week (Monday, Wednesday, and Friday) for 24 weeks.
The primary outcome measured was changes in FEV1 from day 0 (baseline) to the completion of therapy (day 168).
The investigators reported a nonsignificant increase in FEV1 of 0.02 L with azithromycin therapy compared with placebo, and no significant changes in other measures of pulmonary function during the course of the study.
Compared with those receiving placebo, participants receiving azithromycin experienced a 50% reduction in pulmonary exacerbations; 21% of those in the azithromycin group and 39% of those in the placebo group experienced an exacerbation during the course of the study.
The rate of initiation of new oral antibiotics was 27% lower in the azithromycin group compared with the placebo group. Hospitalization rates, as well as rates of intravenous or inhaled antibiotics, were comparable between the 2 groups. Azithromycin-treated participants experienced greater increases in weight and body mass index than those who received placebo.
There were no significant changes in the microbiology of sputum samples obtained during the course of the study, although azithromycin was associated with an increase in treatment-emergent macrolide-resistant Staphylococcus aureus and macrolide-resistant Haemophilus influenzae. Sputum samples to test for nontuberculosis mycobacteria (NTM) were only obtained in 31 azithromycin and 23 placebo participants at baseline, and 32 azithromycin and 19 placebo participants at follow-up. No cases of treatment-emergent NTM were reported.
In evaluating safety, the investigators reported 13 treatment-emergent, serious adverse events in the azithromycin group and 18 in the placebo group. The events were consistent with complications of CF. Cough and productive cough were significantly more common in participants treated with placebo compared with those treated with azithromycin.
Potential study limitations identified by the study authors included the fact that participants had mild lung disease. In addition, participants could have been misclassified as being uninfected with P aeruginosa because only oropharyngeal cultures were obtained. The authors also cautioned that although no cases of NTM were reported, the actual risk of NTM with therapy could not be fully assessed because so few sputum samples were obtained. They added that changes in quality of life or patient-reported outcomes were not included in the study.—Kristina Woodworth