Antibiotics Overused in Acute Asthma Attacks

Adding azithromycin treatment to standard medical care offers no clinically important benefit for patients with acute asthma exacerbations, according to a new study.

“In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics,” wrote the researchers, led by Sebastian L. Johnston, MBBS, PhD, of the National Heart and Lung Institute, Imperial College London.

The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial was a multicenter study of adults who requested emergency care for acute asthma exacerbations that ran from September 2011 to April 2014. The researchers recruited adults who had a history of asthma for more than 6 months within 48 hours of presentation to medical care with an acute deterioration in asthma control that required a course of oral or systemic corticosteroids or both.

A total of 199 asthma patients, mean age 40 years, were randomized to the macrolide azithromycin 500 mg/d or placebo for 3 days. The primary outcome was diary card symptom score 10 days after randomization.

The results showed no difference between azithromycin treatment and placebo in the primary outcome. From exacerbation to day 10 after randomization, mean asthma symptom scores decreased from 4.14 to 2.09 in the azithromycin group and from 4.18 to 2.20 in the placebo group.

There were no significant differences between the groups in secondary outcomes, including quality-of-life questionnaires, lung function measurements during exacerbation, and time to 50% reduction in asthma symptoms.

Adverse events were not frequent in either group. There were more GI events in the azithromycin group (35 events) than in the placebo group (24 events).

Originally, the researchers screened 4582 patients at 31 centers, but 2044 (45%) were excluded from the trial because they had already received antibiotics. This is contrary to treatment guidelines that recommend against routine antibiotic use. The researchers noted that the study’s outcomes may have been affected by high antibiotic use rated and the exclusion of patients who might have benefited from antibiotic therapy for asthma exacerbations.

The researchers published their results in the September 19, 2016 JAMA Internal Medicine.

In an accompanying editorial, Guy G. Brusselle, MD, PhD, and Eva Van Braeckel, MD, PhD, both from Ghent University Hospital, Belgium, stated, “There is a need for novel therapies which-as add-on treatments to systemic corticosteroids-could hasten clinical and functional recovery in patients experiencing an asthma attack and prevent complications.”

The authors contrasted the negative results from the AZALEA trial with the positive results from a study that showed clinical benefit of telithromycin treatment compared with placebo in acute asthma attacks. They suggested that the powerful anti-inflammatory effects of systemic corticosteroids may have masked the beneficial anti-inflammatory effects of macrolides.

They also noted that 22% of acute asthma visits in the United States result in an antibiotic prescription and that this inappropriate use probably contributes to the rising problem of antibiotic resistance. They believe in restricting the use of antibiotics to the patients with acute exacerbations who will benefit the most.