Episode Details

Reference:  Denninghoff KR et al. Azithromycin for Preschoolers with Wheezing in the Emergency Department. New England Journal of Medicine. May 2026 Date: July 14, 2026 Dr. Zara Ibrahim Guest Skeptic: Dr. Zara Ibrahim is a pediatric emergency medicine fellow at Children’s National Hospital in Washington DC where she also completed medical school, pediatric residency. Her research interests include AI applications in medicine and health equity. In her time off, Zara likes to read books, travel, go on long walks to explore DC's excellent bakery scene, and do HIIT workouts to balance out the pastries. Case: A 3-year-old with a history of recurrent wheezing presents to the pediatric emergency department (ED) with cough, rhinorrhea, increased work of breathing, and expiratory wheeze. His Pediatric Respiratory Assessment Measure (PRAM) score is 6. He receives albuterol, ipratropium, and dexamethasone with some improvement. His parents ask: “Last time he was sick, someone gave him antibiotics, I think it was ‘Zith something. Would antibiotics help him get better faster?” Background: Preschool wheeze is best viewed as a heterogeneous clinical syndrome rather than a single diagnosis. Some of these children wheeze mainly during viral illnesses, some may be manifesting an early asthma phenotype, and a smaller number have alternative causes such as bronchiolitis, foreign-body aspiration, anatomic airway abnormalities, etc. Wheezing and asthma exacerbations are frequent reasons for ED care and hospitalization in children. In U.S. data from 2012 to 2020, asthma hospitalization rates were consistently highest among children aged 0 to 4 years and decreased across successive pediatric age groups. During an acute asthma-like episode, airway inflammation, mucosal edema, mucus hypersecretion, and bronchial smooth-muscle constriction further narrow the airways.  This can produce expiratory wheeze, prolonged expiration, tachypnea, retractions, reduced air entry, and, in more severe episodes, hypoxemia. Viral respiratory infections are the most common triggers of acute wheezing and asthma exacerbations in young children, with rhinovirus and respiratory syncytial virus among the frequently identified pathogens. Because preschool children can’t typically perform reproducible spirometry, emergency clinicians rely on clinical examination, pulse oximetry, and validated bedside severity scores such as the Pediatric Respiratory Assessment Measure, or PRAM. The PRAM is a bedside score from 0 to 12 based on oxygen saturation, suprasternal retractions, scalene-muscle contraction, air entry, and wheezing; higher scores indicate greater severity. The immediate ED goal is to rapidly assess exacerbation severity, identify impending respiratory failure, and reassess the child’s response to treatment, rather than assign a permanent diagnostic label during a single acute visit. Standard management includes inhaled short-acting beta₂-agonists, early systemic glucocorticoids for moderate-to-severe exacerbations when appropriate, supplemental oxygen for hypoxemia, and repeated clinical assessment. Antibiotics are not routinely recommended for an asthma-like exacerbation unless there is a separate bacterial indication. Two biologically plausible arguments have been advanced in support of azithromycin. First, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are often detected in the upper airways of young children, and observational studies have associated colonization or microbiome profiles dominated by these organisms with more severe lower respiratory illness and later recurrent wheeze or asthma. These associations raised the hypothesis that bacteria may contribute to some episodes, but nasopharyngeal detection can represent colonization and, by itself, does not establish lower-airway bacterial infection or causation. Second, macrolides have immunomodulatory and anti-inflammatory actions distinct from their antibacterial activity.