Adding azithromycin to the standard antibiotic treatment for early Pseudomonas aeruginosa infections is associated with fewer pulmonary exacerbations in children with cystic fibrosis (CF), results from a Phase 3 trial show.
Trial findings were published in the study, “Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis: The Optimize Randomized Trial,” in the American Journal of Respiratory and Critical Care Medicine.
Pseudomonas aeruginosa is a type of bacteria that commonly infects the lower airways of CF patients, and is associated with an increased inflammatory response, reduced lung function, increased cost of care, and decreased survival.
The first-line therapy for patients with P. aeruginosa is anti-pseudomonal antibiotics such as tobramycin inhalation solution (TIS), whose effectiveness has been demonstrated in multiple clinical trials. With TIS, early P. aeruginosa infections can be eradicated in up to 90% of cases.
However, P. aeruginosa infections can often recur. In fact, approximately one-third of children experience P. aeruginosa recurrence within 18 to 27 months after its initial eradication. Additionally, almost half of patients who receive eradication therapy experience a pulmonary exacerbation within 18 months.
One potential approach that can complement and improve anti-pseudomonal therapy is the use of traditional antimicrobial therapies, such as azithromycin. Azithromycin has been shown to help improve clinical outcomes by reducing the risk of pulmonary exacerbations.
Researchers designed a trial to investigate whether the addition of azithromycin to TIS in children with CF can reduce the risk of pulmonary exacerbations and prolong the time it takes to P. aeruginosa recurrence.
The Phase 3 OPTIMIZE trial (NCT02054156) was a multicenter, randomized, 18-month trial in children with CF, ages 6 months to 18 years, with early P. aeruginosa infection. Participants received standard TIS along with either azithromycin (110 patients) or a placebo (111 patients) three times a week.
Results showed that the risk of pulmonary exacerbations was reduced by 44% in patients treated with both azithromycin and TIS, compared with patients treated with placebo and TIS.
Additionally, the weight of patients treated with azithromycin and TIS increased by an average of 1.27 kg, compared with patients treated with placebo and TIS over the 18-month period.
No significant differences were found in P. aeruginosa recurrence across both groups, indicating that treatment with azithromycin has no impact on microbiologic outcomes. There were also no differences in other clinical or safety endpoints.
Based on these results, “azithromycin was associated with a significant reduction in risk of PEx [pulmonary exacerbations] and sustained improvement in weight but had no impact on microbiologic outcomes in children with early Pa [P. aeruginosa],” the researchers concluded.
“Given the association between exacerbation risk and morbidity over the lifetime of individuals with CF, azithromycin may be a therapeutic option for children with CF and early Pa infection,” they said.