Azithromycin Slows Lung Function Decline in CF Patients with P. aeruginosa, Study Says

Prolonged use of the antibiotic azithromycin resulted in a 37% slower rate of lung function decline in cystic fibrosis (CF) patients with persistent Pseudomonas aeruginosa infection over a three-year period, a study found.

The study, “Pulmonary Outcomes Associated with Long-Term Azithromycin Therapy in Cystic Fibrosis,” was published in the American Journal of Respiratory and Critical Care Medicine.

CF is a genetic condition that results in the buildup of thick mucus in certain organs, including the lungs. This makes the lungs more vulnerable to respiratory infections, and the most common infectious agent in these cases is the bacterium P. aeruginosa.

Because many CF patients experience chronic infections, the antibiotic azithromycin is commonly prescribed for long-term use. Roughly 70% of CF patients with P. aeruginosa infections take azithromycin regularly.

Support for a long-term regimen of azithromycin treatment comes from clinical trials demonstrating health improvements in CF patients with P. aeruginosa over a six-month period. However, little is known about the health benefits of azithromycin over longer periods of time.

A team led by researchers at the Cystic Fibrosis Therapeutics Development Network Coordinating Center at Seattle Children’s Hospital analyzed data collected from the U.S. CF Foundation Patient Registry, which contains information from more than 30,000 American patients with CF — over 95% of the CF patient population in the U.S.

The registry includes data on treatments and clinical outcomes from more than 130 CF care centers nationwide.

The researchers selected 4,715 people with CF between the ages of 6 and 40 who had data available for at least five consecutive years of follow-up, and verifiable information about the presence of P. aeruginosa infection. Of these, 1,474 were positive, and 3,241 were negative for P. aeruginosa.

Researchers matched patients who were taking azithromycin with those who were not, using an algorithm that relied on factors including demographics, health indicators, and treatments. This resulted in 752 P. aeruginosa-positive and 814 P. aeruginosa-negative patients used for the comparison, with half of each group taking azithromycin.

The researchers used data from pulmonary function tests to compare the lung functionality of CF patients who were on azithromycin with those who were not.

In the P. aeruginosa-positive group, the researchers identified a significant reduction in lung function decline, over a three-year period, in the group of patients who had been taking azithromycin.

The findings indicated that long-term azithromycin treatment can slow the decline of lung functionality by 37% in P. aeruginosa-positive CF patients.

No such reduction in lung function decline was observed in the CF patient group who was P. aeruginosa-negative, suggesting that azithromycin only provides long-term benefits in lung function in patients with recurring P. aeruginosa infection.

Researchers then looked at data on the use of antibiotic injections to treat acute pulmonary exacerbations, a CF symptom characterized by the increase of lung-related effects like coughing, sputum (saliva and mucus) production, and shortness of breath.

Previous six-month clinical trials data identified a potential decrease in the risk of pulmonary exacerbations in P. aeruginosa-negative CF patients taking azithromycin.

In this three-year study, however, researchers found that azithromycin seems to have no significant impact on the risk of pulmonary exacerbations, in both P. aeruginosa-positive and negative groups.

The team also investigated a recent finding that azithromycin could have an adverse interaction with tobramycin, an inhaled antibiotic also prescribed to treat lung infections in CF patients. This is also being investigated in CF patients enrolled in the TEACH clinical trial (NCT02677701).

Researchers collected data from 3,902 CF patients taking tobramycin, and 872 taking aztreonam lysine, another inhaled antibiotic. They used two different inhaled antibiotics to compare the effect of azithromycin in each patient group.

Each antibiotic group was split in half, with one half taking low doses of azithromycin and the other taking higher doses. The patients in each half were matched by similar criteria as the previous patient matching.

Azithromycin treatment was not associated with a slower lung function decline in the tobramycin group, whereas it was in the aztreonam lysine group. The results suggested that azithromycin was not providing the same health benefits identified in the study to patients who were also taking tobramycin.

“These data add to the existing literature supporting chronic AZM [azithromycin] therapy in people with CF chronically infected with PA [P. aeruginosa],” the researchers wrote. “A reduction in the rate of decline in lung function…in those infected with PA by 37% is notable, and we are pleased to find such benefit when considering long-term use of a common treatment option.”