Mupirocin (MUP) is a topical antibiotic derived from Pseudomonas fluorescens, widely used for the treatment of superficial skin infections and decolonization of methicillin-resistant Staphylococcus aureus (MRSA). Its unique mechanism of action, selective inhibition of bacterial isoleucyl-transfer RNA synthetase, confers high specificity with minimal risk of cross-resistance to other antibiotic classes. This narrative review provides an updated overview of MUP's chemical structure, mechanism of action, clinical efficacy, resistance mechanisms, and global resistance trends based on literature published from 2017 to 2024. Recent clinical studies confirm MUP's continued effectiveness, particularly in the decolonization of MRSA nasal infections. However, resistance, including high-level MUP resistance mediated by the mupA and mupB genes, is increasingly reported worldwide. A better understanding of resistance patterns and judicious use of MUP is essential to preserving its clinical utility in the context of rising antimicrobial resistance.
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