Treatment weeks 17 to 62 most effective for azithromycin in children with bronchiectasis

Key takeaways:

• From weeks 17 to 62 of treatment, azithromycin was highly effective in children with bronchiectasis.
• Birth before vs. at or after 37 weeks’ gestation linked to smaller declines in exacerbation with azithromycin.

Children with bronchiectasis taking azithromycin had the greatest benefits from weeks 17 to 62 out of 105 weeks of treatment, according to study results published in CHEST.

Further, factors that change the effects of azithromycin, such as preterm birth, were identified, according to researchers.

“Given its importance, both pediatric and adult bronchiectasis guidelines recommend azithromycin for those with frequent exacerbations,” Don Vicendese, PhD, of the allergy and lung health unit at Melbourne School of Population & Global Health, and colleagues wrote. “However, azithromycin is also associated with airway and other pathogens acquiring macrolide resistance. Thus, key gaps remain, and the European Respiratory Society clinical practice guideline for managing children and adolescents with bronchiectasis recommended research to identify those who are most likely to benefit from azithromycin and defining its optimum treatment duration. This study attempted to address these gaps and has important implications for clinical practice and future bronchiectasis guidelines.”

In a secondary analysis of a prior randomized controlled trial that found azithromycin taken regularly long-term decreases exacerbations in patients with bronchiectasis, Vicendese and colleagues analyzed 89 indigenous children with bronchiectasis unrelated to cystic fibrosis to figure out when azithromycin shows the greatest treatment benefits and the factors that can possibly change its efficacy.

Azithromycin was given to 45 children (38% aged younger than 3 years; 58% boys), and placebo was given to 44 children (37% aged younger than 3 years; 48% boys) in order to measure treatment differences.

Researchers found the most effective time period of the drug through semi-parametric Poisson regression and potential modifiers through multivariable Poisson regression that included 23 factors.

Over the median period of 102 weeks [interquartile range, 74-105], researchers found that children receiving azithromycin had less exacerbations per child-week from weeks 4 to 96 than children receiving placebo. By the end of the study, placebo patients experienced a total of 195 exacerbations, whereas azithromycin patients only experienced a total of 104 exacerbations.

Weeks 17 to 62 of receiving azithromycin demonstrated the highest efficacy when calculating the difference between placebo and azithromycin. Compared with the weeks prior to the 17th week and after the 62nd week, researchers found two times (95% CI, 1.1-3.8; P = .034) the treatment difference in mean per child-week exacerbation rate at 17 weeks. Further, at week 62, they saw a 1.8 times (95% CI, 1.04-3.1; P = .037) higher difference in treatments.

Of the 11 factors identified as effect modifiers of azithromycin, the researchers reported four were significant in modifying its effects positively, whereas one was significant in modifying its effects negatively.

Researchers found greater declines in respiratory exacerbations with azithromycin in children with nasopharyngeal carriage of bacterial pathogens vs. those without these pathogens (incidence rate ratio [IRR] = 0.29; 95% CI, 0.2-0.44 vs. 0.81; 95% CI, 0.57-1.14; P < .001), children from New Zealand vs. children from Australia (IRR = 0.39; 95% CI, 0.28-0.55 vs. 0.73; 95% CI, 0.51-1.03; P = 0.12), children with S. pneumoniae at baseline vs. those without it (IRR = 0.36; 95% CI, 0.2-0.63 vs. 0.66; 95% CI, 0.48-0.9; P = .017) and children with increased weight-for-height z scores (IRR = 0.82; 95% CI, 0.67-0.99; P = .044).

Further, nonsignificant modifying factors showing greater benefits of the drug included wheeze at baseline, no wheeze in past 12 months, no previous use of azithromycin, presence of M. catarrhalis at baseline and one bacterial species at baseline vs. none or 2 to 3.

The only significant factor found that was linked to less declines in exacerbations with azithromycin was being born preterm vs. full term (< 37 weeks’ gestation vs. 37 weeks’ gestation; IRR = 0.74; 95% CI, 0.49-1.1 vs. 0.41; 95% CI, 0.3-0.55; P = .012). Additionally, a nonsignificant factor associated with receiving less benefit from azithromycin was not being breastfed.

“Azithromycin-responsive and less-responsive phenotypes likely exist as, compared with their counterparts, children carrying bacterial pathogens in their nasopharynx, having wheeze at baseline, or high current body weight benefited more, whereas children born preterm or not having been breastfed benefited less,” Vicendese and colleagues wrote. “Although these azithromycin-related phenotype data are insufficient to change current clinical practice, they deserve further evaluation in future studies.”