Azithromycin May Improve Childhood Wheezing Episodes

Acute wheezing episodes are common in preschool children. Up to 14-26% of preschoolers have recurrent wheezing in the first 6 years. These episodes result in unscheduled visits to clinician offices, urgent care centers, and emergency room departments, and place significant stress on families. New treatment approaches that would lessen the intensity of these episodes would be extremely beneficial. There is recent exciting evidence that the antibiotic azithromycin may improve these wheezing episodes.

There is also clearly a rationale for the use of antibiotics like a azithromycin for the prevention of wheezing episodes. Research shows that viral infections, especially rhinovirus infections, cause many of these episodes, but there is also evidence that bacteria may be involved. Macrolide antibiotics such as azithromycin are known to have both antimicrobial , as well as anti-inflammatory effects.

The results of the CARE Network’s Azithromycin for Preventing the Development of Upper Respiratory Tract Illness Into Lower Respiratory Tract Symptoms in children study (also called the APRIL study) was recently published. 607 children, aged 12 through 71 months with histories of recurrent, severe lower respiratory tract infections with minimal symptoms in between infections/exacerbations, were randomly assigned to receive azithromycin (12 mg/kg per day for 5 days) or placebo early in the course of a respiratory tract illness that the parents /guardians defined as a child’s usual starting point before development of a severe lower respiratory tract infection. The primary outcome variable was the number of treated respiratory tract infections not progressing to a severe lower respiratory tract infection. The main finding is that the azithromycin–treated children experienced a significant lower risk of progressing to a severe lower respiratory tract infection than the placebo–treated children (p=0.04).
A recent study from Denmark shows similar findings. Dr. Jacob Stokholm, and his colleagues conducted a randomized, double–blind, placebo–controlled trial from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. 158 children aged 1-3 years of age with recurrent asthma–like symptoms were randomized to receive azithromycin (10 mg/kg x3 days), or placebo, early in the course of an episode of troublesome lung symptoms lasting at least 3 days. The main finding was that the symptom duration was shortened by 63% in the azithromycin-treated group (p<0.0001).

The authors from the first study suggest that clinicians may consider a trial of azithromycin in children with recurrent intermittent wheeze early during the course of acute episodes, and if effective, to consider repeating such therapy with subsequent illnesses. This may make more sense in children with multiple frequent episodes.

More studies are certainly needed to define how to translate these findings into clinical care. Concerns regarding the development of antibiotic resistance, as well as potential deleterious alterations in bowel flora must also be taken into consideration.

  1. Barcharier, L. et. al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses. A randomized clinical trial. JAMA 2015:314:2034-2044
  2. Cohen, Robyn et. al. Individual benefit versus societal effect of antibiotic prescribing for preschool children with recurrent wheeze. JAMA 2015:314:2027-9.
    3. Stokholm, J. et. al. Azithromycin for episodes with asthma–like symptoms in young children aged 1-3 years: A randomized, double –blind, placebo–controlled trial. Lancet Respiratory Medicine 2016; 4: 19–26.