Home Analysis COPD exacerbation? Consider azithromycin

COPD exacerbation? Consider azithromycin

March 2012

Published in the March 2012 issue of Today’s Hospitalist

WHEN HOSPITALISTS go to discharge a patient they have been treating for a COPD exacerbation, they should consider adding one more daily pill to the medical regimen.

According to a study published last year in the New England Journal of Medicine, taking 250 mg of azithromycin (Zithromax) once a day for a year is one of the best things COPD patients at risk for an acute exacerbation can do to ward off future episodes.

Lead author Richard K. Albert, MD, a pulmonologist and chief of medicine at Denver Health, says the large, multiyear, multicenter, NIH-funded study proved both the efficacy and the safety of adding the macrolide antibiotic to COPD treatment regimens. Contrary to expectations, the study found that even when a generally older population took once-a-day azithromycin, there were no GI problems.

And while the medication was associated with a small decrement in hearing, that was frequently reversible ” even when the medication was continued.

Both the study and the accompanying editorial concluded that the benefits of taking daily azithromycin outweighed the risks. One of the study’s most surprising findings, Dr. Albert adds, is that while a greater percentage of patients taking the antibiotic for a year (compared to those on placebo) had macrolide-resistant organisms cultured from nasal swabs, the antibiotic markedly reduced nasal colonization. That meant that there were actually fewer subjects with macrolide-resistant organisms in the treatment group.

Role for hospitalists
Hospitalists often treat the subset of COPD patients targeted in the study: those who have suffered at least one acute exacerbation that brought them to the hospital within the previous year and/or those requiring supplemental oxygen. (The study did not look at whether the treatment strategy could benefit COPD patients not prone to exacerbations.)

According to Dr. Albert, the possibility of adding the medication to a patient’s chronic regimen provides an opportunity for hospitalists to discuss that decision with the patient’s primary care physician. While a discharge from a hospital is a good time to start long-term therapy, he adds, it really requires a conversation with the outpatient provider.

He recommends that hospitalists give primary care physicians a call and say, ” ‘Would you like me to start azithromycin on this patient at this point in time?’ This is a great opportunity for something to be discussed between the two treating physicians.”

Additionally, Dr. Albert says, hospitalists should always double-check a diagnosis of COPD exacerbation. In his experience, many patients are admitted with dyspnea from causes other than acute exacerbations “pneumonia, pulmonary embolism, acute laryngospasm “that can mimic COPD exacerbation symptoms.

Acute COPD exacerbations are not only among the most common causes of hospital admission, but they have also been associated with a lower quality of life, higher mortality and a greater decrease in pulmonary function. Although traditional treatments “inhaled corticosteroids and long-acting beta-agonists and muscarinic antagonists “reduce the frequency of acute exacerbations, the study notes that patients taking all three of these medications “may still have as many as 1.4 acute exacerbations, on average, a year.”

An additive effect
Because most COPD patients who experience an acute exacerbation are already in treatment, researchers wanted to replicate that real-world scenario. The study allowed the more than 1,100 patients enrolled in 17 sites around the country to continue their usual treatment, which typically included inhaled corticosteroids plus beta-agonists or muscarinic antagonists. Patients then added a daily azithromycin or placebo for one year.

“Azithromycin clearly worked, and it worked well,” says Dr. Albert. Also, he says, the effect was “additive,” meaning that the macrolide further reduced the risk of an exacerbation on top of the risk reduction provided by inhaled corticosteroids, beta-agonists and anti-muscarinics. Azithromycin reduced patients’ risk of suffering an acute exacerbation by approximately 25%.

Dr. Albert admits that he and his team had several major safety concerns about giving macrolides to this population for such a long time. Because hearing loss has been reported with all macrolide antibiotics, researchers tested all patients’ hearing regularly during the course of the study.

Some decrement was seen, he says, but rates were similar between the two groups: About 25% of the participants in the azithromycin arm lost some hearing, compared to 20% of those in the placebo group. Moreover, he says, hearing improved, regardless of whether the drug was stopped in many patients in both treatment groups. A future paper currently in the works will further explore those data on hearing loss.

“These are older people,” says Dr. Albert. “It should not be a surprise that they had a hearing decrement over a year.” If some hearing loss occurs, he adds, “it is a very small effect and “as best as we could ascertain “it was not progressive and was frequently reversible.”

A question of resistance
The other major question was whether the therapy might further antibiotic resistance. “Any time you give an antibiotic for a long period of time,” Dr. Albert says, “you have to be concerned.”

The study found, however, that half the patients enrolled in both arms of the study had sputum that was already colonized with macrolide-resistant pathogens even before the intervention group started taking azithromycin.

“Resistance to macrolide antibiotics in the community is already out of the barn,” Dr. Albert points out.

Moreover, the study found that while a greater percentage of patients in the azithromycin arm became colonized with macrolide-resistant organisms, taking azithromycin markedly decreased the incidence of colonization. As a result, fewer subjects in the treatment arm became colonized with resistant organisms. (This was simply colonization; neither group had a problem with developing pneumonia.)

The study also found that concerns about troublesome gastrointestinal side effects “most notably, the kind of diarrhea patients often get from macrolide antibiotics “didn’t pan out. According to Dr. Albert, that was a problem for only 1% to 2% of patients in both study groups.

His conclusion is that the therapy’s benefits far outweigh its risks and side effects. “In the right patient population,” says Dr. Albert, “it is a very useful addition to the treatment of COPD.”

Deborah Gesensway is a freelance writer who covers U.S. health care from Toronto.