Long-term treatment with macrolides — a class of antibiotics — is associated with a significant reduction in the frequency of exacerbations in people with bronchiectasis, a study shows.
The study, titled “Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis,” was published in the journal The Lancet Respiratory Medicine.
Guidelines for bronchiectasis treatment indicate that patients who experience three or more exacerbations per year, but don’t have infection with the bacteria Pseudomonas aeruginosa, should undergo long-term macrolide treatment. Macrolides are antibiotics that inhibit the growth of bacteria, and are often prescribed to treat common bacterial infections.
Several randomized controlled trials have suggested that long-term macrolide treatment can prevent exacerbations in adults with bronchiectasis. However, all these studies have been too small to make strong conclusions about the effect of such antibiotic treatment in subpopulations of bronchiectasis patients.
Therefore, an international team of researchers conducted a systematic review and meta-analysis to explore the benefits of macrolide treatment in subgroups of bronchiectasis patients, including those for which macrolide therapy is not currently recommended.
The primary endpoint of the study was the frequency of exacerbations that required antibiotic treatment. Secondary endpoints included time to first exacerbation, quality of life as per the St. George’s Respiratory Questionnaire (SGRQ), and change in FEV1 (a validated measure of lung function).
Using several databases, researchers were able to identify multiple double-blind, randomized, placebo-controlled clinical trials testing macrolide treatment in adults with bronchiectasis.
Researchers divided these patients into subgroups based on a myriad of factors, including their age, gender, previous frequency of exacerbations, smoking status, use of inhaled corticosteroid (anti-inflammatory therapy), body-mass index (BMI), C-reactive protein (an indicator of inflammation), baseline FEV1, SGRQ total score, and status of Pseudomonas aeruginosa infection.
Among the 234 studies identified, the team analyzed three randomized controlled trials. Individual patient data was obtained from 341 participants in the Netherlands, New Zealand, and Australia.
Results indicated that treatment with macrolides for 6-12 months reduced the frequency of exacerbations by almost half. The researchers also found that macrolide treatment increased the time to first exacerbation, and was associated with improved quality of life as measured by the SGRQ.
However, macrolide treatment was not associated with a significant improvement in lung function, as assessed through FEV1.
Importantly, statistical analyses indicated that there was a reduced frequency of exacerbations across all the subgroups analyzed. Notably, researchers found a high level of treatment benefit in individuals with Pseudomonas aeruginosa infections, and in patients with one-to-two exacerbations per year.
“Macrolides had a significant and clinically meaningful impact in patients in whom macrolides are not currently considered as first-line treatment, including those with P. aeruginosa infection and patients with fewer than three exacerbations per year,” the researchers said.
“This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful,” the team added.
Nonetheless, the researchers emphasized the importance of taking into account the downsides of long-term macrolide treatment. They also noted that the longer-term efficacy and safety of macrolides in this population is unknown, as no studies were identified with a treatment duration of more than one year.
Clinicians and patients should have an “individualised discussion of the risks and benefits of macrolides,” the investigators recommended.
“Macrolides have important adverse events, and the potential to induce antimicrobial resistance, so should be used judiciously,” they said.