A randomized controlled trial recently published in JAMA Internal Medicine has reaffirmed the ineffectiveness of azithromycin to treat asthma attacks.
In spite of this finding and prior recommendations, a substantial number of patients with asthma are actively receiving antibiotics treatments for their condition, according to Sebastian L. Johnston, PhD, professor of respiratory medicine and allergy at the National Heart and Lung Institute, Imperial College London, and colleagues.
“A remarkable finding of this study was the number of patients excluded because they were already receiving antibiotic therapy for their asthma exacerbation despite treatment guidelines recommending that such therapy not be routinely given,” they wrote. “For each patient randomized, more than 10 were excluded for this reason. This important finding has obvious and worrying implications regarding antibiotic stewardship.”
It was unclear whether the antimicrobial or anti-inflammatory properties of macrolide antibiotics could aid asthma exacerbations. Due to its additional evidence of antiviral properties, Johnston and colleagues randomly assigned adults with a documented history of asthma to receive 500 mg azithromycin or placebo. The researchers administered treatment or placebo daily for 3 days, conducted posttherapy assessments on days 5 and 10, and sampled serum from the patients after 6 weeks. The primary outcome was diary card asthma symptom scores (range: 0-6), with secondary outcomes including standardized questionnaire scores, forced vital capacity, peak expiratory flow, forced expiratory volume and time to 50% improved symptoms. The study’s exclusion criteria included oral or systemic antibiotic use within 28 days of enrollment, intensive care, other lung diseases and long-term use of more than 20 mg oral corticosteroid daily.
Johnston and colleagues screened 4,582 patients from 31 sites, identifying 390 eligible patients and randomizing 199. The recruitment period was longer and more difficult than initially planned, they wrote, due to the large proportion of asthma patients already receiving antibiotics (44.6% of screened patients). The mean age of the participants was 39.9 years; 69.8% were female. Baseline characteristics were similar across treatment arms and recruitment centers, and 80% of patients attended all follow-up visits.
Mean asthma symptom scores for the intervention group were 4.14 at baseline and 2.09 at day 10, compared with scores of 4.18 and 2.2, respectively, for the control group (difference, –0.166; 95% CI, –0.67 to 0.337). There were no significant differences between the groups’ symptom scores on any day of the study, nor among any of the other secondary outcomes. Adverse events were infrequent among both groups, although gastrointestinal and cardiac events were more common in the intervention group while respiratory, thoracic and mediastinal events occurred more frequently among controls.
These data suggest “no statistically significant or clinically important benefit” related to clinical symptoms, quality-of-life or lung function following azithromycin therapy, the researchers concluded.
In a related editorial, Guy G. Brusselle, MD, PhD, and Eva Van Braeckel, MD, PhD, both of the department of respiratory medicine at Ghent University Hospital, Belgium, compared these results from Johnston and colleagues with a previous study suggesting clinical benefit with telithromycin therapy. They wrote that the studies’ contradicting results could be the result of concurrent infection and inconsistent study design. However, the “most striking finding” of the study was the frequent use of antibiotics to treat asthma attacks, they wrote.
“Inappropriate use of antibiotics for acute asthma has been documented in EDs in several countries including the United States, where 22% of acute asthma visits resulted in an antibiotic prescription, and is likely to contribute to increased bacterial antibiotic resistance,” Brusselle and Van Braeckel wrote. “Restricting the use of antibiotics to those patients with acute exacerbations who will benefit the most is therefore paramount.” – by Dave Muoio
Disclosures: Johnston reports relationships with AstraZeneca, Boehringer Ingelheim, Centocor, Chiesi, GlaxoSmithKline, Merck, Novartis, Roche/Genentech, Sanofi Pasteur and Synairgen, as well as nine licensed patents and one pending patent. Brusselle and Van Braeckel report no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.