Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial.

Summary of Mayer-Hamblett N et al. Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial. Am J Respir Crit Care Med. 2018 Nov 1;198(9):1177-1187. doi: 10.1164/rccm.201802-0215OC.

It is common in children with cystic fibrosis (and PCD) to culture Pseudomonas aeruginosa (Pa), a pathogen that infects the lower airways. This bug is often treated with inhaled antipseudomonal antibiotics, such as tobramycin inhalation solution (TIS). TIS treatment has proven effective in clearing Pa in children, but the risk of recurring Pa growth and subsequent pulmonary infections remains high. The OPTIMIZE trial was conducted to determine if the addition of azithromycin to inhaled tobramycin in children with CF and new isolation of pseudomonas aeruginosa would decrease the risk of pulmonary exacerbation and prolong the time to reoccurrence. While not considered the most effective treatment for pathogens like Pa, azithromycin has been noted for its anti-inflammatory properties.

This multi-center, randomized, double-blind, placebo-controlled study tracked children with CF and a recent positive Pa culture, aged 6 months to 18 years, over the course of 18 months. Of the 227 children screened, 221 were deemed eligible and received either azithromycin (10mg up to 500mg) or a placebo three times per week, in addition to standard TIS therapy. The breakdown of the groups were as follows: azithromycin (110 participants) and placebo (111 participants). Respiratory specimens were collected throughout the study to determine Pa-positivity, and only those who cultured Pa positive after the first 28-day treatment quarter remained on TIS protocol.

The primary endpoint of this study measured time to exacerbation, defined as requiring oral or IV antibiotic intervention. The secondary clinical outcomes looked at time to Pa recurrence after initial eradication, frequency of exacerbation and Pa-positive cultures, rates of antibiotic use, hospitalization(s), and changes in height, weight and pulmonary function.

The study showed that azithromycin significantly reduced the risk of pulmonary exacerbation by 44% while improving and/or sustaining the weight in children with recently cultured Pseudomonas aeruginosa. Additionally, the time to exacerbation was delayed in participants taking azithromycin. However, the rate of exacerbation showed no significant difference compared to those receiving the placebo. What’s more, there was no evidence to suggest that azithromycin would reduce the risk of Pa reoccurrence, despite reducing the risk of exacerbation. Finally, no significant improvements in lung function were noted among the azithromycin group.

In conclusion, the OPTIMIZE trial demonstrates the safety and efficacy of azithromycin in the CF patient population. The reduction in pulmonary exacerbations, while not completely understood, may be linked to the anti-inflammatory properties of azithromycin. Although no improvements in lung function were noted, there was a positive correlation in improving and maintaining weight among the azithromycin arm. Moreover, there were no signs of negative drug interactions between the TIS and azithromycin. Because of these factors, as well as the association between exacerbation risk and morbidity among those affected by CF, azithromycin may be a beneficial treatment option for children with CF and Pa-positive cultures.

NOTE: This study was designed and conducted for children with CF, so we can only speculate as to how azithromycin with TIS therapy would impact the PCD population. As always, please consult with your physician regarding treatment therapies and protocols.