Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin-resistant Staphylococcus aureus in some settings. In this study, we provide experimental proof of coselection for multidrug resistance in S. aureus following exposure to FA or mupirocin. Through targeted mutagenesis and phenotypic analyses, we confirmed that fusC carriage confers resistance to FA and mupA carriage confers high-level resistance to mupirocin in multiple S. aureus genetic backgrounds. In vitro experiments demonstrated that carriage of fusC and mupA confers a competitive advantage in the presence of subinhibitory concentrations of FA and mupirocin, respectively. Further, we used a porcine skin colonization model to show that clinically relevant concentrations of topical antibiotics can coselect for the presence of unrelated antimicrobial resistance determinants, such as mecA, blaZ, and qacA, in fusC- or mupA-harboring S. aureus. These findings provide valuable insights on the role of acquired FA or mupirocin resistance in coselecting for broader antibiotic resistance in S. aureus, prompting a greater need for judicious use of topical antibiotics.

中文翻译：

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局部抗生素在多重耐药金黄色葡萄球菌共选中的临床相关性：来自体外和离体模型的见解

外用抗生素制剂，例如夫西地酸 (FA) 或莫匹罗星，用于预防和治疗由葡萄球菌引起的浅表皮肤感染。先前的基因组流行病学研究表明，在某些情况下，局部抗生素的广泛使用与耐甲氧西林金黄色葡萄球菌的出现之间存在关联。在这项研究中，我们提供了暴露于 FA 或莫匹罗星后金黄色葡萄球菌多重耐药性共同选择的实验证据。通过靶向诱变和表型分析，我们证实fusC 的携带赋予了对 FA 的抗性，而mupA 的携带赋予了多种金黄色葡萄球菌对莫匹罗星的高水平抗性遗传背景。体外实验表明，在亚抑制浓度的 FA 和莫匹罗星分别存在的情况下，携带fusC和mupA会带来竞争优势。此外，我们使用猪皮肤定植模型表明临床相关浓度的外用抗生素可以共同选择不相关的抗菌素耐药性决定因素的存在，例如 mecA 、 blaZ 和qacA，在fusC-或mupA -窝藏金黄色葡萄球菌. 这些发现为获得性 FA 或莫匹罗星耐药性在共同选择金黄色葡萄球菌更广泛的抗生素耐药性方面的作用提供了宝贵的见解，促使人们更加需要明智地使用局部抗生素。