When guideline treatment of asthma fails, consider a macrolide antibiotic

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Applied Evidence

When guideline treatment of asthma fails, consider a macrolide antibiotic

J Fam Pract. 2019 December;68(10):536-540,542-545

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References

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7. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:659-668.

8. Stokholm J, Chawes BL, Vissing NH, et al. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2016;4:19-26.

9. Korn S, Both J, Jung M, et al. Prospective evaluation of current asthma control using ACQ and ACT compared with GINA criteria. Ann Allergy Asthma Immunol. 2011;107:474-479.

10. Hahn DL. A Cure for Asthma? What Your Doctor Isn’t Telling You—and Why. Durham, North Carolina: Peoples Pharmacy Press; 2013.

11. Hahn DL. Acute asthmatic bronchitis: a new twist to an old problem. J Fam Pract. 1994;39:431-435.

12. Johnston SL, Blasi F, Black PN, et al; TELICAST Investigators. The effect of telithromycin in acute exacerbations of asthma. N Engl J Med. 2006;354:1589-1600.

13. Johnston SL, Szigeti M, Cross M, et al. Azithromycin for acute exacerbations of asthma: the AZALEA Randomized Clinical Trial. JAMA Intern Med. 2016;176:1630-1637.

14. Brusselle GG, Van Braeckel E. AZALEA trial highlights antibiotic overuse in acute asthma attacks. JAMA Intern Med. 2016;176:1637-1638.

15. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycinAsthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

16. Hahn DL. An unanticipated effect of clinical trial registration. BMJ.com. November 2, 2007. https://www.bmj.com/rapid-response/2011/11/01/unanticipated-effect-clinical-trial-registration. Accessed November 2, 2019.

17. Hahn DL. Treatment of Chlamydia pneumoniae infection in adult asthma: a before-after trial. J Fam Pract. 1995;41:345-351.

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20. Rollins DR, Beuther DA, Martin RJ. Update on infection and antibiotics in asthma. Curr Allergy Asthma Rep. 2010;10:67-73.

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22. Hahn DL, Plane MB, Mahdi OS, et al. Secondary outcomes of a pilot randomized trial of azithromycin treatment for asthma. PLoS Clin Trials. 2006;1:e11.

23. Hahn DL, Peeling RW, Dillon E, et al. Serologic markers for Chlamydia pneumoniae in asthma. Ann Allergy Asthma Immunol. 2000;84: 227-233.

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Antibiotic resistance. Exposure of populations to macrolides can increase the percentage of macrolide-resistant bacterial respiratory pathogens³³; policies aimed at decreasing inappropriate macrolide prescribing can significantly lower that percentage.³⁴ There is no evidence, however, of any detrimental effects of macrolide resistance in individual patients receiving azithromycin.³³

Physicians who prescribe long-term azithromycin should instruct patients to report any hearing loss.

In trials of azithromycin for the treatment of trachoma in Africa, significantly fewer deaths occurred in villages where subjects were treated with azithromycin than in villages where azithromycin therapy was not provided.³⁵ In the United States, weekly azithromycin treatment for 3 to 12 months in adults with heart disease resulted in fewer cases of acute bronchitis and pneumonia, compared with the placebo-treated groups^31,32; similar benefit for azithromycin was seen in children who had recurrent lung infection.^8,36

Nevertheless, concern over the spread of macrolide-resistant bacteria to the surrounding community is a concern and a possibility—and should be the subject of future research.

Sudden cardiac death. In a Medicaid population, the risk of sudden cardiac death from taking a macrolide among patients at high risk of cardiovascular disease was 1 in every 4000 administrations.²⁷ Compare that level of risk with the 1 in 167 risk of an acute cardiovascular event in patients with COPD who start taking a LABA.³⁷ There is no detectable increase in the risk of sudden cardiac death when taking azithromycin in the general (ie, average cardiovascular risk) population^38,39 or when azithromycin is coadministered with a LABA.³

Hearing loss. An excess of 18 (< 1%) patients affected by hearing loss, 7 of whom sought medical attention, was reported among 2004 patients who had stable coronary artery disease and had been treated once weekly with azithromycin for 12 months (P = .02, compared with placebo).³² In another study, hearing test changes leading to discontinuation of azithromycin were detected in an excess of 32 (2.8%) of 1142 patients with COPD treated daily for 1 year.¹⁸

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