Thomas Adviti, Almsallaty Nour, Chalati Tamim, Boateng Joshua, Buanz Asma, Totea Ana Maria
School Science, Faculty of Engineering and Science, University of Greenwich, Central Avenue, Chatham ME4 4TB, UK.
Ironstone Centre, HCRG Care Group, NHS, West Street, Scunthorpe, South Humberside DN15 6HX, UK.
Int J Pharm. 2025 Aug 14;684:126030. doi: 10.1016/j.ijpharm.2025.126030.
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.
抗生素通常被用作细菌性皮肤感染的一线治疗药物，尤其是在严重和持续性病例中。然而，病原体产生抗生素耐药性的能力使这些疾病的治疗变得复杂。耐甲氧西林金黄色葡萄球菌（MRSA）是引起皮肤和软组织感染的主要微生物之一，如蜂窝织炎、脓疱病以及特应性皮炎（AD）继发的感染，并且由于其对包括β-内酰胺类在内的传统抗生素具有耐药性，给医疗行业带来了巨大压力。即使没有常见的危险因素，个体也可能感染这种革兰氏阳性超级细菌引起的皮肤感染，因此，迫切需要开发超越传统抗生素作用机制的新型治疗策略。对替代治疗方法的研究，包括植物源化合物、抗菌肽（AMPs）、噬菌体和抗生素增敏剂，作为一种有前景的创新方法正受到关注。大量研究表明这些化合物具有抑制MRSA等病原菌的能力。这些新型化合物通过多种机制靶向细菌，抑制生物膜形成，并减轻耐药性的产生。对于与MRSA相关的皮肤感染，局部给药治疗是首选；然而，细胞毒性、皮肤渗透性和体内疗效测试仍然是重大挑战。本综述概述了导致MRSA皮肤感染发病机制的相关机制，并研究了替代常用抗生素的治疗选择。一种使用传统抗生素与非抗生素联合的间接抗菌方法旨在通过破坏细菌防御和生物膜形成来提高治疗效果并克服耐药性，从而减少所需的抗生素剂量并将不良反应降至最低。
