Long-term use of low-dose macrolide antibiotics is safe and potentially effective in reducing acute exacerbations in younger patients with chronic obstructive pulmonary disease (COPD) who are at risk for poorer outcomes, a review study suggests.
Although this therapeutic regimen was found to be generally well-tolerated, with few side effects, it was found to be unsuitable for elderly patients, the researchers said. Additional studies are therefore warranted to further explore the long-term effects of macrolides in the COPD population.
The study, “Effects of long-term macrolide therapy at low doses in stable COPD,” was published in the International Journal of Chronic Obstructive Pulmonary Disease.
Macrolides are a family of antibiotics that are commonly used to fight infections, and prevent acute respiratory exacerbations (lung disease worsening). Among them are erythromycin, azithromycin, and clarithromycin.
These compounds have also been shown to exert broad-ranging immunomodulatory and anti-inflammatory effects, in addition to their antibiotic properties.
Frequent acute exacerbations are a well-known risk factor for deteriorating respiratory function among patients with COPD. In fact, estimates indicate that approximately half of COPD treatment costs are to manage and resolve acute exacerbations.
About 50% of acute exacerbations in COPD patients are triggered by lung bacterial infections, and are accompanied by airway inflammation. Given the immune- and inflammation-mediated nature of these events, macrolides have been viewed as potential agents to target COPD acute exacerbations. However, when tested in clinical trials, these compounds have failed to demonstrate significant benefits, so their use is not generally accepted for COPD.
To investigate the impact of macrolides on COPD exacerbations, researchers in China reviewed clinical data from 10 previously published studies about the use of these antibiotics. Their analysis included a total of 1,521 COPD patients treated with macrolides, and 1,418 who were not (control group).
Results showed that, compared with a placebo, treatment with macrolide antibiotics could reduce the risk of exacerbations by 23% in COPD patients.
Also, data collected from 1,415 participants (in seven of the studies analyzed) showed that prophylactic use of macrolide could prolong remission time.
“Our meta-analysis has analyzed and confirmed that long-term low dose usage of macrolides could significantly reduce the frequency of the acute exacerbation of COPD,” the researchers wrote.
These findings were confirmed with additional data from nine studies (involving 1,508 patients), which showed that the rate of exacerbations per patient per year was significantly reduced among patients treated with macrolides. Also, the mean number of hospitalizations due to exacerbations was reduced in macrolide-treated patients, according to data from four of the studies.
Erythromycin seemed to be the most effective of the macrolides analyzed in reducing exacerbations, the study suggested.
Macrolide antibiotics were generally safe and well-tolerated in the patients, with the most common adverse events being gastrointestinal reactions, and cardiovascular events. A side effect reported with azithromycin use was hearing impairment.
However, the researchers found that older COPD patients were less likely to respond to treatment with macrolides.
Overall, “long-term low dose usage of macrolides could significantly reduce the frequency of the acute exacerbation of COPD,” the researchers wrote, adding that the “treatment was well tolerated, with few adverse reactions, but it was not suitable for the elderly.”
According to the team, macrolides should be used in younger COPD patients with a “higher risk of acute exacerbation and mortality.”
The team also emphasized that further studies are needed “in order to obtain more comprehensive and objective conclusions on the efficacy of macrolide antibiotics in the treatment of stable COPD.”