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Does Azithromycin Reduce Post-RSV Recurrent Wheeze in Infants?

RESPIRATORY syncytial virus (RSV) is a major cause of lower respiratory disease and hospitalisation in infants worldwide. Moreover, RSV bronchiolitis is a risk factor for childhood asthma. Azithromycin therapy has previously been shown to attenuate RSV-driven airway inflammation; therefore, Avraham Beigelman, Washington University School of Medicine, St. Louis, Missouri, USA, and collaborators investigated whether this antibiotic could reduce recurrent wheeze following RSV infection. 

Beigelman highlighted the importance of conducting the study: “About half of infants admitted to a hospital with RSV will be diagnosed with asthma by age 7.” Consequently, there is interest in finding approaches to prevent the development of asthma after RSV infection. 

With parental permission, the researchers prospectively enrolled 200 otherwise healthy children aged 1–18 months who were hospitalised with RSV bronchiolitis and randomly assigned them to receive either oral azithromycin or placebo for 2 weeks. The primary outcome measure was the occurrence of recurrent wheeze, defined as the third episode of post-RSV wheeze over the ensuing 2–4 years of follow-up. 

Overall, the levels of IL-8 in nasal lavage fluid, which served as a marker of airway inflammation, were lower among azithromycin-treated participants (p<0.01). Despite this, the antibiotic was not found to reduce the risk of post-RSV recurrent wheeze: 47% of patients who received oral azithromycin experienced recurrent wheezing, compared with 36% of the placebo group (p=0.11).  

Commenting on the results, Beigelman noted that “there may be an increase in risk of recurrent wheezing with any antibiotic use.” Beigelman further stressed: “We want to be cautious in our interpretation of this potentially negative effect of antibiotics, as the study was not designed to test the effects of different antibiotics. However, this is an important message to be communicated to pediatricians, since antibiotics are frequently given to patients with RSV bronchiolitis despite the fact that this practice is not supported by clinical guidelines.” 

In conclusion, azithromycin therapy did not reduce recurrent wheeze occurrence over the following 2–4 years. For this reason, Beigelman acknowledged that “azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they are harmful.”