Over-the-counter antibiotics compromising aminoglycoside activity

Robertson, A. ORCID: https://orcid.org/0000-0001-5345-7846, Coutinho, G., Mantzourani, E. ORCID: https://orcid.org/0000-0002-6313-1409, Szomolay, B., Pillay, T., Shephard, A. and Maillard, J. Y. ORCID: https://orcid.org/0000-0002-8617-9288 2024. Over-the-counter antibiotics compromising aminoglycoside activity. Journal of Antimicrobial Chemotherapy 10.1093/jac/dkae376

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Abstract

Introduction Antimicrobial resistance (AMR) is a global issue that needs addressing. While antibiotic stewardship has improved often by restricting antibiotic use, some antibiotics that are still sold legally over the counter (OTC), notably in sore throat medications. Recent findings suggest OTC antibiotics could trigger cross-resistance to antibiotics used in clinical treatments, whether systemic or topical. Here we investigated the impact of three antibiotics contained in OTC sore throat medicines on emerging AMR in vitro. Methods Bacterial pathogens were exposed to a bactericidal concentration of an aminoglycoside in the presence or absence of a during-use concentration of bacitracin, gramicidin or tyrothricin in a time–kill assay. Damage to the bacterial membrane was also investigated by measuring potassium leakage and membrane potential alteration post-OTC antibiotic exposure. Results Gramicidin (15 µg/mL) significantly decreased the bactericidal activity of amikacin, tobramycin or gentamicin in Acinetobacter baumannii. It also decreased gentamicin bactericidal activity in Enterobacter cloacae, Escherichia coli and Klebsiella pneumoniae, while tyrothricin decreased the aminoglycoside efficacy in E. cloacae and E. coli. Gramicidin significantly decreased bacterial membrane potential and caused significant potassium leakage. Conclusion Gramicidin and to some extent tyrothricin impacted aminoglycoside efficacy by affecting membrane potential, which is essential for aminoglycosides uptake. Thus, some OTC antibiotics can interfere with aminoglycoside activity, which could in turn affect treatment efficacy. Although the likelihood of OTC antibiotics and aminoglycosides being used at the same time might not be common, this research highlights one potential reason for OTC antibiotics’ usage to result in treatment failure and their contribution to AMR development.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by-nc/4.0/, Start Date: 2024-10-29
Publisher:	Oxford University Press
ISSN:	0305-7453
Date of First Compliant Deposit:	7 November 2024
Date of Acceptance:	6 October 2024
Last Modified:	12 Nov 2024 12:15
URI:	https://orca.cardiff.ac.uk/id/eprint/173727

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