Azithromycin for Prevention of COPD Exacerbations

Posted by • August 24th, 2011

Summer’s coming to a close and the patient sitting in your office is worried.  A bad cough and wheeze sent him to the hospital for three days last winter, and he feels like he’s never quite gotten back to normal. He stopped smoking a few years ago, and uses the long-acting bronchodilators and inhaled corticosteroids you prescribed. But he still worries about another COPD exacerbation; it seems like each time he gets sick, it’s more difficult to recover.  Is there anything else he can do to make it less likely he’ll get sick again this year?

The answer, according to a study published in this week’s NEJM, is yes. Azithromycin taken daily for a year decreased the frequency of COPD exacerbations and improved quality of life in a cohort with COPD, reports Richard Albert and colleagues.

Why azithromycin? The macrolide antibiotic has anti-inflammatory and immune-modulatory benefits (which is why it is given to patients with cystic fibrosis and bronchiectasis) on top of its antibiotic action. However, studies have been split on the question of whether long-term antibiotics benefit patients with COPD.

Enter the current study, which enrolled 1,142 patients with COPD from 12 academic centers across the United States.  To be eligible for the study, all patients either used continuous supplemental oxygen or had suffered a COPD exacerbation in the past year that required systemic steroids, a visit to the ED or hospitalization. Approximately 80 percent were receiving inhaled corticosteroids and/or long-acting bronchodilators. (Patients with prolonged QTc or hearing loss were excluded from the study – as these are known to be adverse effects associated with azithromycin).

Participants were randomly assigned to take either azithromycin at a 250 mg daily dose or a placebo pill for a year. Those with daily azithromycin stayed exacerbation-free for a significantly longer time: 266 days prior to first exacerbation versus 174 days for those with placebo. There was no statistically significant difference in mortality.  

The daily antibiotic also helped patients’ quality of life, as measured by a commonly used survey which asks about symptoms, activity level and overall comfort. However, taking an antibiotic daily does not come without risk.

The biggest concern, of course, is increasing microbial resistance.  To investigate this question, each patient had nasopharyngeal swabs taken at study visits. More patients in the azithromycin group became colonized with bacteria that were resistant to macrolide antibiotics, but this finding didn’t have any clear clinical significance. It remains unknown what this resistance pattern could mean for patients’ families or community.

Hearing loss was also a potential issue. More patients taking azithromycin than placebo experienced a decrement in their hearing over the year.

In an accompanying editorial, Nikolaos M. Siafakis, a pulmonologist who is the president of the European Respiratory Society, balanced these risks and benefits, and wrote that the study data come out in favor of azithromycin: “The findings of Albert and co-workers…in my opinion turns the balance towards the benefits of azithromycin treatment. However, if azithromycin is going to be used in patients known to be frequent COPD exacerbators, then the local antibiotic resistance patterns should be closely monitored…On balance however the long term use of azithromycin to prevent AECOPD seems to be a risk in accord with the classical advice of Hippocrates – do good – no harm.”

Question:  Would you put the patient in question on long-term azithromycin based on this study?   

6 Responses to “Azithromycin for Prevention of COPD Exacerbations”

  1. Azithromycin may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) arrhythmia.

  2. umesh says:

    i think there should be a comparative study .we have to use other antibiotics also along with Azithromycin,and other group should be without antibiotics.

  3. shankar sharma says:

    I think long term studies should be done to rule out increased incidence of infections due to resistant strains.

  4. docsanjaysarkar says:

    if the above study is true then we r getting another indication for prophylactic antibiotic therapy…but if we say anti inflammatory and immunomodulatory action of azithromycin…then the question is …do we need such when using inhaled corticosteroids?…next is what about coming years…will the patient be affected with a more multidrug resistant organism?…next thing is i want to know during which month the exacerbations have occured in the treatment group and the placebo group…the difference showing a mean gap of around 90 days or 3 months….now if both are during the winter period…then i think the study is to be reevaluated…

  5. chris digregorio says:

    I had a patient that was on a rotating, different antibiotic every other month, throughout each year. This eliminated his copd exacerbations which had caused him multiple hospitalzations. The patient was cared for by a pulmonologist!

  6. krogers58 says:

    After having my GP place me on azithromycin for an exacerbation and feeling the amazing effects, I spoke with him about continuing on Azithromycin. He declined and within a couple of weeks I was again quite congested and on the verge of another exacerbation. I took matters into my own hands and began Azithromycin 1 x day, @ 250mg. Once congestion cleared (usually about 5 days) I would discontinue using it, and wait until it re-appeared. I am now on my own “cycle” of probably 5 days per month or 5 days per 3 weeks. My quality of life has imporved drammatically and I am now able to exercise to achieve even better results. I have noticed that I can now go for more extended periods without using Azithromycin, something on the order of 3 months or so now. To withhold this treatment from patients, given how much better I feel is tantamount, in my opinion, to malpractice. I told my doctor what I’ve been doing and he has come around, given my exacerbations have now dropped to zero in the last year. It had previously been on the order of 6 times per year where I would need IV antibiotics and steroids (oral).