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Published on: April 18, 2019
Over-the-counter antibiotics compromising aminoglycoside activity
A Robertson1, G Coutinho2, E Mantzourani1
1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
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.
Insights
Over-the-counter antibiotics like gramicidin can reduce the effectiveness of essential clinical antibiotics by damaging bacterial membranes. This interference contributes to antimicrobial resistance (AMR) and potential treatment failures.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antimicrobial resistance (AMR) is a critical global health challenge.
- Over-the-counter (OTC) antibiotics, particularly in sore throat remedies, may contribute to AMR.
- Concerns exist that OTC antibiotics could induce cross-resistance to clinically important antibiotics.
Purpose of the Study:
- To investigate the in vitro impact of three antibiotics found in OTC sore throat medications on emerging AMR.
- To determine if OTC antibiotics affect the efficacy of commonly used clinical antibiotics.
Main Methods:
- Bacterial pathogens were subjected to time-kill assays with aminoglycoside antibiotics, alone and with OTC antibiotics (bacitracin, gramicidin, tyrothricin).
- Membrane damage was assessed by measuring potassium leakage and membrane potential alterations after OTC antibiotic exposure.
Main Results:
- Gramicidin significantly reduced the bactericidal activity of amikacin, tobramycin, and gentamicin against Acinetobacter baumannii.
- Gramicidin and tyrothricin diminished aminoglycoside efficacy in other key pathogens like Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae.
- Gramicidin exposure led to significant bacterial membrane potential decrease and potassium leakage.
Conclusions:
- Gramicidin and tyrothricin interfere with aminoglycoside efficacy by disrupting bacterial membrane potential, crucial for drug uptake.
- These findings highlight a potential mechanism by which OTC antibiotics can lead to treatment failure and contribute to AMR development.
- While concurrent use may be uncommon, this study underscores a possible pathway for OTC antibiotic contribution to resistance and treatment efficacy issues.
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