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非处方抗生素会损害氨基糖苷类药物的活性。

Over-the-counter antibiotics compromising aminoglycoside activity.

作者信息

Robertson A, Coutinho G, Mantzourani E, Szomolay B, Pillay T, Shephard A, Maillard J Y

机构信息

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

Medical Marketing, Reckitt Benckiser, Slough, UK.

出版信息

J Antimicrob Chemother. 2025 Jan 3;80(1):87-94. doi: 10.1093/jac/dkae376.

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.

摘要

引言

抗菌药物耐药性(AMR)是一个需要解决的全球性问题。虽然抗生素管理通常通过限制抗生素使用而得到改善,但一些抗生素仍可合法地在非处方(OTC)销售,尤其是在咽喉痛药物中。最近的研究结果表明,OTC抗生素可能引发对临床治疗中使用的抗生素(无论是全身性还是局部性)的交叉耐药性。在此,我们研究了OTC咽喉痛药物中含有的三种抗生素对体外新出现的AMR的影响。

方法

在时间杀灭试验中,将细菌病原体暴露于氨基糖苷类的杀菌浓度下,同时存在或不存在使用期间浓度的杆菌肽、短杆菌肽或硫链丝菌素。还通过测量OTC抗生素暴露后钾泄漏和膜电位变化来研究对细菌膜的损伤。

结果

短杆菌肽(15μg/mL)显著降低了鲍曼不动杆菌中阿米卡星、妥布霉素或庆大霉素的杀菌活性。它还降低了阴沟肠杆菌、大肠杆菌和肺炎克雷伯菌中庆大霉素的杀菌活性,而硫链丝菌素降低了阴沟肠杆菌和大肠杆菌中氨基糖苷类的疗效。短杆菌肽显著降低细菌膜电位并导致显著的钾泄漏。

结论

短杆菌肽以及在一定程度上硫链丝菌素通过影响膜电位影响氨基糖苷类的疗效,而膜电位对于氨基糖苷类的摄取至关重要。因此,一些OTC抗生素可干扰氨基糖苷类的活性,这反过来可能影响治疗效果。虽然OTC抗生素和氨基糖苷类同时使用的可能性可能不常见,但这项研究突出了OTC抗生素使用导致治疗失败的一个潜在原因及其对AMR发展的贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11695918/1b14f4609989/dkae376f1.jpg

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