Antibiotic No Help for Young Kids’ Acute Wheezing

A course of azithromycin for preschoolers who presented to the emergency department (ED) with wheezing didn’t improve their symptoms, the AZ-SWED trial showed.

Among children, ages 18-59 months, the 5-day sum of scores on the Asthma Flare-up Diary for Young Children (ADYC) did not differ significantly compared with placebo in either those who initially tested positive for pathogenic bacteria (median 9.59 vs 9.72, P=0.70) or those who tested negative (9.30 vs 9.10, P=0.69). ADYC scores range from 5-35 points, with higher scores indicating more severe symptoms.

While the trial was stopped early for futility — reducing the statistical power of the trial — it was sufficient to show that “a moderate or large true effect is implausible,” Richard M. Ruddy, MD, of the University of Cincinnati College of Medicine, reported at the American Thoracic Society annual meeting in Orlando. The findings were published simultaneously in the New England Journal of Medicine.

“Wheezing illnesses are a leading cause of hospitalization for preschool-age children and are frequently treated with antibiotics,” the group noted. While most acute wheezing in kids ages older than 1 year involves viral infection, recent studies have suggested a pathogenic role of bacteria in acute lower respiratory illness in this age group, as well a high incidence of the bacteria Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae in nasopharyngeal samples from children with recurrent episodes of wheezing, Ruddy and colleagues wrote.

Putting the AZ-SWED findings together with prior trials that have shown a benefit of azithromycin when initiated early in the course of illness for kids in outpatient settings, but not in 12- to 60-month-olds presenting in the ED, severity of illness might be a key factor in whether the antibiotic helps, Ruddy’s group suggested.

“[W]e speculate that azithromycin may have been more effective in the outpatient setting than in our emergency department cohort with more severe illness owing to the preventive anti-inflammatory effects of the drug, and we suggest that azithromycin should not be used to treat children with established respiratory distress,” the group wrote.

AZ-SWED included 840 patients, ages 18-59 months, who presented to the ED with expiratory wheezing that scored at least 4 on the Pediatric Respiratory Assessment Measure (PRAM, range 0-12).

Children could not have had antibiotics for any reason in the prior 2 weeks or have presented to the ED with an acute infection that required systemic antibiotics.

Participants were randomized to one oral dose of either azithromycin (12 mg per kg of body weight) or matched placebo each day for 5 days. Randomization was stratified by testing for S. pneumoniae, M. catarrhalis, or H. influenzae, which 62% of the children (521) were positive for.

Bacterial clearance and antimicrobial resistance measured at follow-up visits 1-3 weeks after randomization showed that the antibiotic led to bacterial clearance in 58.7% of those who had tested positive, compared with 11.4% clearing bacteria in the placebo group.

Secondary outcomes came out similar between treatment groups, including length of stay in the ED, length of hospital stay, and return ED visits or hospitalizations within 72 hours.

One limitation was testing azithromycin but not other antibiotics due to sample-size constraints and the preliminary evidence that supported azithromycin, “but as noted, the differences in bacterial clearance between the groups do not support a role for antibacterial agents in these episodes,” the researchers wrote.