Which patients with respiratory disease need long-term azithromycin?

EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of death, poor quality of life, and healthcare expenditures.²⁰ Prevention is therefore of the utmost importance.

Several studies have shown that azithromycin prophylaxis can reduce acute exacerbations of COPD. A recent meta-analysis showed that long-term macrolide prophylaxis significantly reduced exacerbations compared with rates in controls (risk ratio = 0.70, 95% CI 0.56–0.87, P < .01) and increased the median time to first COPD exacerbation by more than 90 days (P < .01).²¹ Long-term azithromycin therapy may be considered in selected patients who have frequent exacerbations despite optimal maintenance inhaler therapy.

PROPHYLAXIS IN IMMUNODEFICIENCY

Disseminated Mycobacterium avium complex (MAC) is an opportunistic infection most commonly occurring in patients with acquired immunodeficiency syndrome with CD4 counts below 50 cells/µL.^22,23

In a double-blinded, randomized trial, patients who received azithromycin had a 47% reduction in the incidence of MAC infection.

Given the long half-life of azithromycin, it is effective with once-weekly dosing of 1,200 mg.²³ Ideally, patients are placed on a prophylactic agent for disseminated MAC infection until the CD4 count reaches 100 cells/µL and remains at or above this level for 3 consecutive months.²⁴

ADVERSE EFFECTS AND PRECAUTIONS

Long-term azithromycin therapy may produce bacterial resistance; the risk has been estimated at 2.7 times greater in patients who are on long-term azithromycin treatment.²⁵ Also, patients at risk for MAC infection, such as those with cystic fibrosis, should be screened for it before starting treatment in order to prevent resistance to azithromycin.

The US Food and Drug Administration warns that azithromycin can lead to a prolonged corrected QT interval and potential fatal arrhythmias such as torsades de pointes. Major reviews have largely agreed that arrhythmias are more pronounced in patients with a coexisting cardiac risk factor such as existing QT-interval prolongation, low blood levels of potassium or magnesium, a slower than normal heart rate, or arrhythmias, or who are on class IA and III antiarrhythmic drugs.^26–28

Other potential adverse effects of long-term azithromycin treatment are gastrointestinal symptoms and hearing impairment.^29,30 A review of potential drug interactions is advised when patients are placed on long-term azithromycin therapy.

Although azithromycin is generally well tolerated, long-term treatment should be individualized and the benefits weighed against the risks. Patients should be monitored during treatment for any of the above adverse effects.