Thrice-weekly azithromycin effective for early management of cystic fibrosis in kids: Lancet

Australia: Azithromycin reduces the airway inflammation associated with progressive lung disease in infants with cystic fibrosis (CF) and lessens the duration of their hospital stay, states trial findings published in The Lancet Respiratory Medicine. However, it did not reduce the extent of structural lung disease at 36 months of age.

Findings assure significant change in the trajectory of the disease in young kids who are yet not eligible for medications such as modulator therapies that are used in older children and adults.

Cystic fibrosis (CF) is an inherited life-threatening disorder that damages the lungs and digestive system. In children diagnosed with cystic fibrosis after the newborn screening, structural lung disease and neutrophil-dominated airway inflammation are present from 3 months of age. They are prone to severe lung infections due to thick mucus build-up in their lungs which may lead to multiple long hospital stays and continuous treatment with antibiotics. Azithromycin (commonly prescribed broad-spectrum antibiotic) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis.

Prof Stephen, Wal-yan Respiratory Research Centre, Perth, Australia, and colleagues aimed to determine whether Azithromycin treatment for infants is safe and will prevent the onset of bronchiectasis.

A phase 3, randomized, double-blind, placebo-controlled trial with 130 participants was done at 8 pediatric cystic fibrosis centers in Australia and New Zealand. Infants (aged 3–6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria were prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or co-morbidities other than cystic fibrosis, or macrolide hypersensitivity.

Participants were randomly assigned (1:1). 68 participants received azithromycin (10 mg/kg body weight orally three times per week) and 62 received matched placebo until age 36 months.

Key findings from the study are,

• 88% of the azithromycin group and 94% of the placebo group had bronchiectasis (p=0•32), and total airways disease did not differ between groups.

• The azithromycin group showed fewer days in the hospital for pulmonary exacerbations and fewer courses of inhaled or oral antibiotics.

• The azithromycin group, showed lower concentrations of airway inflammation, including interleukin-8 and neutrophil elastase activity, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months.

• There was no effect on the body-mass index at age 36 months or any evidence of pathogen emergence with the use of azithromycin.

• There were few adverse outcomes with no differences between the treatment groups.

The authors concluded that azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age but it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with the disease. The authors thus suggest thrice-weekly azithromycin as a strategy for the routine early management of paediatric patients with cystic fibrosis.

Reference:

Prof Stephen M. Stick, Alexia Foti, Prof Robert S. Ware et al. https://doi.org/10.1016/S2213-2600(22)00165-5. Published: June 02, 2022. DOI: https://doi.org/10.1016/S2213-2600(22)00165-5