Clinical relevance of topical antibiotic use in co-selecting for multidrug-resistant : Insights from and models.

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 in some settings. In this study, we provide experimental proof of co-selection for multidrug resistance in following exposure to FA or mupirocin. Through targeted mutagenesis and phenotypic analyses, we confirmed that carriage confers resistance to FA, and carriage confers high-level resistance to mupirocin in multiple genetic backgrounds. experiments demonstrated that carriage of and confer a competitive advantage in the presence of sub-inhibitory concentrations of FA and mupirocin, respectively. Further, we used a porcine skin colonisation model to show that clinically relevant concentrations of topical antibiotics can co-select for presence of unrelated antimicrobial resistance determinants, such as , , and , in or harbouring These findings provide valuable insights on the role of acquired FA or mupirocin resistance in co-selecting for broader antibiotic resistance in , prompting greater need for judicious use of topical antibiotics.