key: cord-0935747-wfmy0r96
authors: Kow, Chia Siang; Hasan, Syed Shahzad
title: Use of Azithromycin in COVID-19: A Cautionary Tale
date: 2020-08-20
journal: Clin Drug Investig
DOI: 10.1007/s40261-020-00961-z
sha: 998c1b59bcef5533cfd2c8beb6c76fc416abb918
doc_id: 935747
cord_uid: wfmy0r96

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resistance towards azithromycin and other related macrolides is associated with active macrolide efflux pumps produced by the bacteria [3] . Active macrolide efflux pumps are encoded by the macrolide efflux genes MSRA and MSRB. These efflux pumps are part of the bacterial systems involved in the extrusion of molecules from bacteria to the environment, including bacterial products such as siderophores, as well as toxic compounds and macrolide antibiotics.

Similar to resistance with other antimicrobial agents, widespread and unrestricted use has been associated with the development of resistance towards azithromycin and other related macrolides. Such association was directly illustrated in a controversial randomised, double-blind trial in which 224 healthy volunteers were assigned to either azithromycin, clarithromycin, or placebo to determine the development of pharyngeal carriage of macrolide-resistant streptococci [4] . At baseline, the proportion of macrolide-resistant streptococci was 26-30%. Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with placebo, peaking at days 4-8, with a mean increase of approximately 50% (to an absolute proportion of more than 80%), compared with 4% with placebo. Indeed, the increase in resistance was greater with azithromycin compared with clarithromycin, possibly due to its much longer half-life.

We have observed increasing resistance of azithromycin towards Treponema pallidum, the causative pathogen of syphilis, which therefore renders azithromycin out of favour as the treatment option for this infection [5] . History may repeat itself if we do not practice judicious use of azithromycin. With the possible more widespread use of azithromycin to treat COVID-19, we may lose azithromycin in our antimicrobial armamentarium to treat bacterial infections, for which the role of azithromycin has been well-established, including community-acquired pneumonia, non-tuberculous mycobacterial infections, and Group A streptococcal pharyngitis. We urge clinicians managing patients with COVID-19 to factor into consideration the possible development of acquired resistance when prescribing azithromycin, especially in regions where azithromycin resistance is already a concern.

Azithromycin for COVID-19: More Than Just An Antimicrobial?

Macrolides and ketolides: azithromycin, clarithromycin, telithromycin

Distribution of genes encoding resistance to macrolides, lincosamides and streptogramins among clinical staphylococcal isolates in a Turkish university hospital

Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study

Global challenge of antibiotic-resistant Treponema pallidum