Antibiotic proves ineffective in treating wheezing in young children in the emergency room: Study

A study led by researchers at the University of Arizona College of Medicine – Tucson showed that giving the antibiotic azithromycin did not help preschool children seen in the hospital emergency room with bouts of severe wheezing.

The results from a Phase 3 clinical trial provide more definitive answers to longstanding questions and inconclusive studies about the role of some types of bacteria in wheezing and asthma, and how to effectively treat these conditions.

The trial, Azithromycin Therapy in Preschoolers with a Severe Wheezing Episode Diagnosed at the Emergency Department, or AZ-SWED, compared the effects of azithromycin to a placebo given randomly to 840 children between the ages of 18 and 59 months at eight pediatric emergency departments across the country.

Children received either the drug or a placebo for five days and were evaluated through a standard tool called the Asthma Flare-up Diary for Young Children, or ADYC, score, which relies on parents' daily assessment of a child's breathing, coughing, appetite, mood and other characteristics.

The trial results were reported May 18 in The New England Journal of Medicine and presented at the American Thoracic Society meeting at the same time in Orlando.

Wheezing and asthma are responsible for the highest rates of hospitalization in children under five years old, with approximately 30,000 admissions in the U.S. annually. Approximately 2.2 million children in the U.S between ages two and five years old need to visit emergency rooms each year for wheezing episodes. For some kids, wheezing is a condition that lessens over time. For others, it's the first sign of asthma.

Children with frequent episodes of wheezing also are more likely to harbor potentially harmful bacteria growing in their throats, including Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae.

One of the key questions the study was meant to answer was whether the presence of such bacteria in the nasopharynx was related to wheezing. In the trial, 521 of the 840 children tested positive for at least one kind of possibly harmful bacteria.

The trial was stopped early after an interim analysis indicated the antibiotic wasn't improving wheezing symptoms. ADYC scores didn't differ significantly between the azithromycin and placebo groups. Looking more closely, the researchers didn't find any difference in the ADYC scores between the children who received the drug and those with the placebo in children who carried the harmful bacteria when they were in the emergency department.

"We can say with a high degree of certainty that children who come to the doctor's office or the emergency room with a severe wheezing episode should not be given azithromycin or any antibiotic," said lead researcher Dr. Fernando Martinez, director of the U of A Asthma and Airway Disease Research Center, Regents Professor and Swift-McNear Professor of Pediatrics in the College of Medicine – Tucson.

Martinez, who also is a member of the BIO5 Institute, said that studies to date on antibiotic use in children with wheezing haven't considered if they carried the three types of bacteria.

"We've been saying for years that antibiotics should not be used in these acute situations because the wheezing is caused by viruses," he said. "But clinicians still use antibiotics at least a quarter of the time in these young children."

The overuse of antibiotics raises concerns about drug resistance, as well as the potential impact on the development of children's immunity from normal exposure to bacteria.

In young children, wheezing is often accompanied by respiratory virus infections, including the common cold. Most of the children in the study who were seen in emergency departments (slightly more than 86%) also carried one or more of these viruses, with 72.5% infected with a cold virus.

Martinez said the importance of viral infections in wheezing and asthma can't be overstated.

"If you treat these children with antibiotics when they are already sick with a virus, you don't get any improvement," he said. "The fact that the children with the pathogenic bacteria didn't respond to the antibiotic – even if we eradicated the bacteria – challenges the idea that bacteria cause the wheezing. The bacteria are probably there because the children have a susceptibility."

Martinez thinks that children might be especially affected by the cold virus and are harboring bacteria because they have compromised immune systems. He suggested that "the bacteria are taking advantage of the fact that the child has an inappropriate response to the virus," and not because they are causing the wheezing.

Martinez and his team are following up with studies aimed at better understanding the potential virus-wheezing relationship in preschool children.

"We want to know why the cold virus causes a runny nose and other symptoms in most children," he said, "but in this group the virus appears to contribute to wheezing and hospitalization."

Reference:

Kurt R. Denninghoff, Azithromycin for Preschoolers with Wheezing in the Emergency Department, New England Journal of Medicine, DOI: 10.1056/NEJMoa2516505