November 25, 2015
Early Initiation of Azithromycin Beneficial for Some
Pediatric RTIs

St. Louis—Despite campaigns to avoid prescribing broad-spectrum antibiotics to children with respiratory tract infections unless a bacterial cause can be established, every rule has its exceptions.

A new study finds that, among young children with histories of recurrent severe lower respiratory tract illness (LRTI), the early use of azithromycin significantly reduces the risk of progression to severe LRTI, compared to placebo.

Background in the article, published recently in the Journal of the American Medical Association, notes that acute episodes of severe LRTI are common among preschoolers, and up to 14% to 26% have medical visits related to recurrent wheezing during the first 6 years of life. Those episodes can be so severe that parents and caregivers often end up seeking urgent or emergency care for the sick children.

Researchers from the Washington University in St. Louis School of Medicine point out that while viral infections often are coexistent, bacteria can contribute to illness development. In light of that, the study team sought to identify treatment approaches to lessen the severity of the LRTI episodes.

During the trial, 607 children—from a year old through almost 6 years old—with histories of recurrent, severe LRTIs were randomized to either receive azithromycin for 5 days or a matching placebo, initiated early during each predefined RTI. Individualized action plans determined each child’s signs or symptoms prior to development of LRT. Participants were from nine academic U.S. medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network.

Most, 443, of the children became ill for a total of 937 RTIs—473 in the azithromycin group compared to 464 in the placebo group. Of those, 92 were severe LRTIs, 35 in the azithromycin group, 35 and 57 in the placebo group.

Results indicate that the azithromycin group experienced a significantly lower risk of progressing to severe LRTI than the placebo group, with infrequent adverse events, according to study authors.

“We want to be prudent with our antibiotic use,” said lead author Leonard B. Bacharier. “We don't want to overdo this. On the other hand, these are children having severe episodes for which we don’t have a lot of effective therapy. A significant number are getting an antibiotic therapy anyway and have to be very sick to get it. Our study suggests we can reduce the risk of severe respiratory illnesses by giving azithromycin treatment earlier.”

To monitor the development of antibiotic-resistant organisms, the study team looked at azithromycin resistance in a subset of 86 patients seen at St. Louis Children's Hospital.

“We saw that there were children who received azithromycin during the study who, at the end of the study, had azithromycin-resistant germs in their throats,” Bacharier explained in a Washington University School of Medicine press release. “But we also saw, at nearly but not quite the same rate, azithromycin-resistant bacteria in children who did not receive any of the antibiotic. So we don't fully understand the effect of azithromycin on antibiotic resistance.”

Study authors further suggest that “real-world rates of development of azithromycin-resistant organisms may be greater, potentially due to failure to complete the full duration of therapy often seen in clinical practice.” They also call for more research, including comparing the benefits of early azithromycin with either daily or intermittent high-dose inhaled corticosteroids.

An accompanying editorial from Robyn T. Cohen, MD, MPH, and Stephen I. Pelton, MD, of the Boston University School of Medicine suggests, “Limiting children’s loss of days from school (or parents’ days from work) and relieving the anxiety that an RTI that may progress to a hospitalization is almost certainly to be of benefit to children and families.”

The commentators emphasize that the question is how to determine, using techniques such as biomarkers, airway endotyping or genetics to determine “which children are most likely to obtain the largest benefit from early initiation of azithromycin. Until a higher-risk population can be prospectively identified (rather than all children with intermittent wheezing associated with viral RTI) for progression to severe LRTI, the consequences of widespread use of azithromycin, both known and hypothesized, outweigh the benefit for most children.”

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