Azithromycin and Structural Lung Disease in Newborns With Cystic Fibrosis

A newborn, preterm infant
A newborn, preterm infant
Will azithromycin, given 3 times weekly to infants with cystic fibrosis from diagnosis until age 36 months, reduce damage from structural lung disease?

Among newborns diagnosed with cystic fibrosis, immediate treatment with azithromycin lessened hospitalizations, death, pulmonary exacerbations, and airway inflammation but did not diminish the spread of structural lung disease recorded at 36 months of age, according to research findings published recently in The Lancet Respiratory Medicine.

Neutrophilic airway inflammation, typically present by 3 months in infants with cystic fibrosis, is often accompanied by bronchiectasis and progressive airway disease, with or without lower airway infection. High-dose ibuprofen is an effective anti-inflammatory for cystic fibrosis and may slow or prevent the decline of lung function in children but is generally not prescribed for infants. Researchers sought to evaluate azithromycin as a therapy for preventing the spread of lung disease in newborns with cystic fibrosis.

Investigators for the current study conducted a phase 3, placebo-controlled, double-blind, randomized trial ( Identifier: NCT01270074) from June 2012 to July 2017 that included 130 infants (3 to 6 months of age) at 8 pediatric cystic fibrosis centers in New Zealand and Australia, of whom 68 participants received azithromycin 10 mg/kg of bodyweight 3 times per week orally, and 62 received matched placebo. Newborns on prolonged mechanical ventilation or with significant comorbidities were excluded. The primary endpoints were lung volume affected by disease and the proportion of participants with bronchiectasis.

In the azithromycin cohort, 50 participants (88%) had bronchiectasis at 36 months compared with placebo 44 participants (94%) with bronchiectasis (odds ratio 0.49; 95% CI, 0.12-2.00; P =.32). No significant difference was seen between cohorts in total airways disease (median difference –0.02%; 95% CI, –0.59 to 0.56; P =.96). Participants in the azithromycin cohort required fewer doses of antibiotics (incidence rate ratio 0.88; 95% CI, 0.81-0·97; P =.0088) and had fewer pulmonary exacerbation hospital days (mean difference –6.3; 95% CI, –10.5 to –2.1; P =.0037). Azithromycin treatment showed no indication of pathogen emergence and few adverse outcomes, with no difference between cohorts.

Researchers concluded that, “Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalizations, and improved some clinical outcomes associated with cystic fibrosis lung disease.” For newborn patients with cystic fibrosis, they recommend early management with azithromycin.

Study limitations include the low resolution of the ultralow-dose CT scan which could detect early disease, the underpowered sample, nonstandardized or unavailable testing equipment, and miscalculation either of necessary placebo sample size or of participants with bronchiectasis prior to initiation of treatment. Also, adherence was not monitored and therefore assessed via pharmacy records and parental reporting.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Stick SM, Foti A, Ware RS, et al; COMBAT CF Study Group. The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomized, double-blind, placebo-controlled clinical trial. Lancet Respir Med. Published online June 2, 2022. doi:10.1016/S2213-2600(22)00165-5