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In vitro activity and pharmacodynamic/pharmacokinetic parameters of clarithromycin and azithromycin: why they matter in the treatment of respiratory tract infections

Authors Davidson RJ

Received 11 September 2018

Accepted for publication 27 December 2018

Published 8 March 2019 Volume 2019:12 Pages 585—596


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Eric Nulens

Ross J Davidson1–4

1Department of Pathology and Laboratory Medicine, Division of Microbiology, Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada; 2Department of Medicine, 3Department of Pathology, 4Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada

Abstract: Clarithromycin and azithromycin are second-generation macrolides established and widely used for treating a range of upper and lower respiratory tract infections. Extensive clinical trials data indicate that these drugs are highly effective in these applications and broadly comparable in their clinical and microbiological effectiveness. However, consideration of pharmacokinetic, metabolic, and tissue-penetration data, including the significant antibacterial activity of the metabolite 14-hydroxy-clarithromycin, plus the findings of pharmacodynamic modeling, provide evidence that the long half-life and lower potency of azithromycin predispose this agent to select for resistant isolates. Comparison of the “mutant-prevention concentrations” of clarithromycin and azithromycin, and examination of large-scale epidemiological data from Canada, also support the view that these drugs differ materially in their propensity to promote resistance among bacterial strains implicated in common respiratory infections, and that clarithromycin may offer important advantages over azithromycin that should be considered when choosing a macrolide to treat these conditions.

Keywords: azithromycin, clarithromycin, 14-hydroxy-clarithromycin, mutant prevention concentration, pharmacokinetics, tissue-penetration, upper respiratory tract infection, lower respiratory tract infection

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