Azithromycin fails to prevent recurrent wheeze among infants hospitalized with RSV

PHOENIX — Azithromycin failed to prevent infants with severe respiratory syncytial virus, or RSV, from later developing recurrent wheeze, according to data presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

“About half of infants admitted to a hospital with RSV will be diagnosed with asthma by age 7,” Avraham Beigelman, MD, associate professor of pediatrics and a pediatric allergist and immunologist in the division of allergy and pulmonary medicine in the department of pediatrics at Washington University School of Medicine in St. Louis, said in a press release. “We are interested in finding approaches to prevent the development of asthma after RSV infection. Azithromycin has anti-inflammatory effects in other airway diseases, such as cystic fibrosis.

“We also had data in mice and data from a smaller clinical trial of hospitalized infants that suggested azithromycin reduced wheezing following RSV infection,” Beigelman added. “So, we were surprised by the negative results of this larger trial.”

The analysis included data of 200 otherwise healthy babies hospitalized with RSV bronchiolitis. After stratifying patients for use of open-label nonmacrolide antibiotics during the preceding 2 weeks, researchers randomly assigned the patients to receive 10 mg/kg oral azithromycin, an antibiotic, for 7 days followed by 5 mg/kg daily for 7 days (n = 101; median age, 3.9 months; range, 2.3-7.2; 53.5% boys; 18.8% white) or placebo (n = 99; median age, 2.8 months; range, 1.7-6.6; 55.6% boys; 13.1% white).

Researchers followed the children for 2 to 4 years.

Occurrence of recurrent wheeze, defined as a third episode of wheeze following RSV, served as the study’s primary outcome.

Overall, results showed that use of the antibiotic failed to reduce incidence of recurrent wheeze (HR = 1.45; 95% CI, 0.92-2.29). This finding persisted in a subanalysis of patients who had not received other antibiotics within 14 days prior to randomization (HR = 1.79; 95% CI, 1.03-3.1) as well as among those who had received other antibiotics (HR = 0.94; 95% CI, 0.43-2.07).

A post-hoc analysis also showed no difference in time to recurrent wheeze among participants who received placebo and no other antibiotics compared with patients who received any antibiotics (HR = 1.65; 95% CI, 1-2.72).

This finding suggests that any antibiotic exposure during severe RSV bronchiolitis, whether azithromycin or other nonmacrolide antibiotics, may actually augment the development of recurrent wheeze, according to the researchers.

“We want to be cautious in our interpretation of this potentially negative effect of antibiotics, as the study was not designed to test the effects of different antibiotics,” Beigelman said. “However, this is an important message to be communicated to pediatricians, since antibiotics are frequently given to patients with RSV bronchiolitis despite the fact that this practice is not supported by clinical guidelines. At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they are harmful.”

Despite the lack of impact of the study’s primary outcome, an exploratory analysis showed patients assigned azithromycin had significantly lower levels of IL-8 in the upper airway (P = .003).

The researchers plan to conduct additional analyses of airway microbiome and stool samples collected from the infants to identify any markers that may play a role in future wheezing and asthma, according to the press release.

Reference:

• Antibiotic doesn’t prevent future wheezing in babies hospitalized with RSV. https://www.newswise.com/articles/antibiotic-doesn-t-prevent-future-wheezing-in-babies-hospitalized-with-rsv?sc=cwhr&xy=10013298. Published Feb. 27, 2022. Accessed Feb. 27, 2022.