Role of methicillin-resistant Staphylococcus aureus in cutaneous infections: Current treatments and therapeutic approaches for future advancement.

Antibiotics are often prescribed as a first-line treatment for bacterial skin infections, particularly in severe and persistent cases. However, the ability of the pathogen to develop antibiotic resistance complicates the treatment of these diseases. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the primary microorganisms implicated in skin and soft tissue infections, such as cellulitis, impetigo, and infections secondary to atopic dermatitis (AD) and has exerted significant pressure on the healthcare industry due to its resistance to conventional antibiotics, including beta-lactams. Skin infections caused by this Gram-positive superbug can occur in individuals even without commonly known risk factors, and thus, there is an urgent need to develop novel therapeutic strategies that function beyond traditional antibiotics. Research on alternative treatments, including plant-derived compounds, antimicrobial peptides (AMPs), bacteriophages, and antibiotic sensitisers, is garnering attention as a promising and innovative approach. Numerous studies have demonstrated the capacity of these compounds to inhibit pathogenic bacteria such as MRSA. These novel compounds target bacteria through diverse mechanisms, inhibit biofilm formation, and mitigate resistance development. Topically administered treatments are preferred for MRSA-related skin infections; however, cytotoxicity, skin penetration, and in vivo efficacy testing remain significant challenges. This review provides an overview of the mechanisms contributing to the pathogenesis of MRSA skin infections and investigates alternative therapeutic options to the common antibiotics. An indirect antibacterial approach that uses conventional antibiotics combined with non-antibiotics aims to enhance therapeutic efficacy and overcome resistance by disrupting bacterial defences and biofilm formation, thereby reducing the required antibiotic dosage and minimising adverse effects.