Antibiotic doesn't prevent future wheezing in babies hospitalized with
RSV
Study of azithromycin suggests antibiotics do not prevent wheezing after
RSV infection; may have opposite effect

Date:
February 28, 2022
Source:
Washington University School of Medicine
Summary:
Antibiotics provide no benefit in preventing future recurrent
wheezing in babies hospitalized with respiratory syncytial virus
(RSV), according to a new study. And there is some evidence that
antibiotics may make wheezing worse.



FULL STORY ==========================================================================
The antibiotic azithromycin has anti-inflammatory properties that can be beneficial in some chronic lung diseases, such as cystic fibrosis. With
that in mind, researchers investigated its potential to prevent future recurrent wheezing among infants hospitalized with respiratory syncytial
virus (RSV).

With such babies at increased risk of developing asthma later in
childhood, the scientists hoped to find a therapy to reduce this risk.


========================================================================== However, among infants hospitalized with RSV, there was no difference in
the amount of wheezing in babies treated with azithromycin versus those
who received a placebo, according to a new study led by researchers at Washington University School of Medicine in St. Louis and Vanderbilt University.

Further, while the difference in the amount of wheezing did not reach statistical significance, the study hints that treatment with antibiotics
of any kind may increase wheezing in infants hospitalized with the virus.

Results of the study were presented Feb. 27 at the annual meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix and published simultaneously in The New England Journal of Medicine -- Evidence.

In infants and young children, RSV can cause bronchiolitis, an infection
of the small airways in the lungs. Nearly all children contract RSV
at some point in early childhood, and a small percentage develop
bronchiolitis severe enough to be hospitalized. Infants hospitalized
with RSV bronchiolitis are at an increased risk of developing asthma.

"About half of infants admitted to a hospital with RSV will be
diagnosed with asthma by age 7," said first author Avraham Beigelman,
MD, an associate professor of pediatrics and a pediatric allergist
and immunologist in the Division of Allergy & Pulmonary Medicine in the Department of Pediatrics at Washington University School of Medicine. "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. So, we were
surprised by the negative results of this larger trial." The current
trial confirmed, as anticipated, that azithromycin lowers a marker of
airway inflammation called IL-8. Infants treated with azithromycin
had lower levels of IL-8 in their noses than infants who received a
placebo, confirming anti-inflammatory effects of azithromycin. Even so, azithromycin-treated patients did not have reduced risk of developing
recurrent wheezing compared with the placebo group. While the difference
did not reach statistical significance, the data actually leaned toward azithromycin increasing risk of wheezing, with 47% of patients who
had received azithromycin experiencing recurrent wheezing versus 36%
of the placebo group. Recurrent wheezing was defined as three episodes
of wheezing during the two to four years of follow up.



==========================================================================
With parental permission, the researchers randomly assigned 200 infants hospitalized at St. Louis Children's Hospital for RSV bronchiolitis to
receive either oral azithromycin or a placebo for two weeks. The babies
were otherwise healthy and ranged in age from 1 month to 18 months. The researchers received approval from the Food and Drug Administration (FDA)
to give infants azithromycin as part of this clinical trial. Azithromycin
is a commonly prescribed antibiotic used in children age 2 and older.

Patients were enrolled during three consecutive RSV seasons, from 2016 to
2019, and were followed for two to four years after hospitalization. The researchers also kept track of whether the infants received any other antibiotics before or during their hospital stays. A child's pediatrician
could choose to prescribe other antibiotics if, for example, the child
also developed an ear infection or was suspected of developing bacterial pneumonia or other bacterial infection.

Amoxicillin was the most common additional antibiotic prescribed.

While the study was not designed to parse the effects of different
combinations of antibiotics, Beigelman said they found evidence suggesting
that azithromycin alone -- among patients who did not receive any
other antibiotics -- could increase the risk of recurrent wheezing. The researchers also found a suggestion of increased recurrent wheezing risk
among patients who had received any antibiotic (such as amoxicillin from
the pediatrician).

"There may be an increase in risk of recurrent wheezing with any
antibiotic use," Beigelman said. "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. 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." Beigelman said the researchers
also collected airway microbiome samples from these patients and plan
to investigate whether bacteria colonizing the airway may interact
with the antibiotics and have an impact on wheezing. They also plan to
analyze stool samples collected from the same infants to see whether
the gut microbiome may have a role in wheezing and the subsequent risk
of developing asthma in childhood.

This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH), grant number
R01HL130876.

========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Julia
Evangelou Strait. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Avraham Beigelman, Mythili Srinivasan, Charles W. Goss, Jinli Wang,
Yanjiao Zhou, Kelly True, Elizabeth Ahrens, Dana Burgdorf,
Matthew D.

Haslam, Jonathan Boomer, Sarah Bram, Carey-Ann D. Burnham,
Timothy J.

Casper, Andrea M. Coverstone, Watcharoot Kanchongkittiphon,
Cadence Kuklinski, Gregory A. Storch, Meghan A. Wallace,
Huiqing Yin-DeClue, Mario Castro, Kenneth B. Schechtman, Leonard
B. Bacharier. Azithromycin to Prevent Recurrent Wheeze Following
Severe Respiratory Syncytial Virus Bronchiolitis. NEJM Evidence,
2022; DOI: 10.1056/EVIDoa2100069 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220228091151.htm

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