Azithromycin does not reduce illness severity in preschoolers with severe wheezing

Key takeaways:

• Azithromycin for 5 days was studied against placebo.
• Futility analyses stopped this trial early.
• Being negative or positive for bacteria considered pathogenic did not change the illness severity finding.

SAN FRANCISCO — Illness severity of preschoolers presenting to the ED for severe wheezing did not differ between 5-day azithromycin and placebo, according to data presented at the American Thoracic Society International Conference.

“Azithromycin did not decrease the severity of wheezing illnesses in these children, even if they were positive for bacteria that are considered usually pathogenic in this age group,” Fernando D. Martinez, MD, Regents’ Professor, director of the asthma and airway disease research center and Swift-McNear Professor of Pediatrics at the University of Arizona, said during his ATS presentation.

In the randomized, placebo-controlled, precision-medicine AZ-SWED trial, Martinez and colleagues assessed 832 children (61.5% boys; 47.7% Black/African American) aged 18 months to less than 60 months presenting to the ED for severe wheezing to determine the impact of once daily 12 mg/kg azithromycin, an antibiotic, for 5 days vs. placebo on illness severity via the validated Asthma Flare-up Diary for Young Children score.

Researchers separated the population into those positive for Streptococcus pneumoniae, Hemophilus influenzae or Moraxella catarrhalis using baseline nasopharyngeal samples and those negative for these bacteria when assessing outcomes.

“Several studies have reported more frequent isolation of Streptococcus pneumoniae, Hemophilus influenzae and/or Moraxella catarrhalis from nasopharyngeal secretions of preschool children with acute wheezing episodes than in controls not having such episodes,” Martinez said.

According to the presentation, a greater proportion of the study cohort had vs. did not have one of these bacteria (62%; n = 520 vs. 37%; n = 312).

“The normal number that you find of carriers is approximately 30% in the population, so twice as much as in the population as a whole,” Martinez said.

Both the bacterial and non-bacterial groups had similar proportions of males (61.3% and 61.9%) and Black/African American children (44.8% and 52.6%).

Martinez noted that once approximately 60% of all subjects were randomly assigned to azithromycin or placebo, a futility analysis for each study group took place.

“Even in the least plausible, most optimistic scenarios, conditional power was 16% or less,” he said during the presentation. “In other words, we found no effect, and this was true both for the positive and for the negative children.”

When assessing azithromycin vs. placebo in those positive for one of the studied bacteria, researchers reported no significant difference in the cumulative Asthma Flare-up Diary for Young Children score over 5 days. This was also the case in the children negative for the assessed bacteria.

“Both groups in positive or negative were equally severe during the period, and there was no change in the severity of the disease during the 5 days that we conducted this study,” Martinez said.

Dividing the score by day of treatment also yielded comparable results between those receiving azithromycin and those receiving placebo in both the bacterial group and the non-bacterial group, according to the study.

Martinez highlighted that “50% of the children who were randomized to this study were hospitalized,” and researchers compared hospital length of stay of children receiving azithromycin with that of children receiving placebo. Similar to the above findings, this outcome did not differ when the azithromycin group was placed against the placebo group, and this was the case in both those positive and those negative for bacteria.

Additionally, bacterial clearance was analyzed 1 week following ED discharge in positive children. Researchers found a higher proportion of children with clearance of all present bacteria in the azithromycin group vs. the placebo group (58.7% vs. 11.4%).

“The antibiotic was moderately effective in decreasing colonization in these children,” Martinez said.

Martinez and colleagues also assessed bacterial resistance at 1 to 3 weeks following ED discharge and found “no evidence of increased bacterial resistance.”

“We speculate emphatically that these children should not be treated with antibiotics if they don’t have any other cause latter to their wheezing that would justify the use of azithromycin,” Martinez said.