Macrolides Side Effects

The COPD Clinical Research Network (CCRN) researchers were particularly concerned about two potential side effects known to be associated with the use of macrolides—hearing loss and heart complications.

The researchers excluded people who had measurable hearing loss at the start of the study. As an additional safeguard they tested the hearing of study participants throughout the study. The findings at the end of the study confirmed earlier suspicions—azithromycin can adversely affect hearing. The researchers noted hearing loss in 25 percent of azithromycin users and in 20 percent of those who weren't using it—a small but significant difference.

Earlier studies have also shown that macrolide antibiotics have the potential to exacerbate heart disease. As a precaution, the researchers excluded anyone with signs of an irregular heartbeat (arrhythmia) or who used medications that could lead to such an irregularity. At the end of study, treatment did not appear to induce cardiovascular problems.

But a more revealing and concerning finding comes from another study reported in The New England Journal of Medicine. Investigators reviewed the records of more than 3 million hospitalized adults; nearly 350,000—many of whom were likely to have heart disease—had been treated with azithromycin. The investigators reported a slightly increased risk of cardiovascular death and sudden death among patients who received a five-day course of azithromycin when compared with people treated with the antibiotics amoxicillin or ciprofloxacin, or no antibiotic. Another antibiotic, levofloxacin (Levaquin) produced results similar to azithromycin.

Antibiotic Resistance

Another important concern—what effect would prolonged use of antibiotics have on the rise of drug-resistant bacteria? Warnings that antibiotic overuse is leading to antibiotic resistance are being issued with increasing frequency and urgency. Could prophylactic use of azithromycin contribute to bacterial resistance among patients and among the larger community?

To answer the first part of this question, the CCRN researchers checked the airways of people in both groups for the presence of bacteria. As expected, they found more new bacterial colonies in individuals who received the placebo. But the development of macrolide-resistant bacteria was twice as high in the group that received azithromycin; 81 percent and 41 percent, respectively.

As alarming as that sounds, there is some debate about whether bacteria in the respiratory system are likely to be harmful. They could, as bacteria sometimes do, lie dormant, causing no problems. That appears to be the case in the CCRN study, as the bacteria were not found to be responsible for any pneumonia or other serious illness during the year of treatment.

But what if those resistant bacteria escape their host and infect others in the community? The researchers did not attempt to answer that question, so it remains a significant concern.

Publication Review By: Peter B. Terry, M.D., M.A.

Published: 24 Jun 2013

Last Modified: 24 Jun 2013