The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is difficult to kill with a single antibiotic because it has evolved to be resistant to various antibiotics by increasing the PBP2a (mecA) expression level, building up biofilm, introducing SCCmec for multidrug resistance, and changing its membrane properties. Therefore, to overcome antibiotic resistance and decrease possible genetic mutations that can lead to the acquisition of higher antibiotic resistance, drug combination therapy was applied based on previous results indicating that MRSA shows increased susceptibility to free fatty acids and surfactants. The optimal ratio of three components and the synergistic effects of possible combinations were investigated. The combinations were directly applied to clinically isolated strains, and the combination containing 15 μg/mL of oxacillin was able to control SCCmec type III and IV isolates having an oxacillin minimum inhibitory concentration (MIC) up to 1024 μg/mL; moreover, the combination with a slightly increased oxacillin concentration was able to kill SCCmec type II. Phospholipid analysis revealed that clinical strains with higher resistance contained a high portion of 12-methyltetradecanoic acid (anteiso-C15:0) and 14-methylhexadecanoic acid (anteiso-C17:0), although individual strains showed different patterns. In summary, we showed that combinatorial therapy with a low concentration of oxacillin controlled different laboratory and highly diversified clinical MRSA strains.

中文翻译：

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低浓度奥沙西林与棕榈酸和Span85的联合治疗可控制耐甲氧西林的金黄色葡萄球菌

抗生素的过度使用导致了多重耐药细菌的出现，例如耐甲氧西林的金黄色葡萄球菌（MRSA）。MRSA很难用一种抗生素杀死，因为它已经通过增加PBP2a（mecA表达水平，建立生物膜，引入SCCmec来实现多药耐药性，并改变其膜特性。因此，为了克服抗生素抗性并减少可能导致更高抗生素抗性获得的遗传突变，基于以前的结果表明MRSA对游离脂肪酸和表面活性剂的敏感性增加，因此进行了药物联合治疗。研究了三种成分的最佳比例和可能组合的协同效应。将该组合直接应用于临床分离的菌株，并且包含15μg/ mL的奥沙西林的组合能够控制具有高达1024μg/ mL的奥沙西林最低抑菌浓度（MIC）的SCCmec III型和IV型分离株。此外，与奥沙西林浓度稍微增加的组合能够杀死II型SCCmec。磷脂分析显示，尽管个别菌株表现出不同的模式，但具有较高耐药性的临床菌株含有较高比例的12-甲基十四烷酸（前异C15：0）和14-甲基十六烷酸（前异C17：0）。总之，我们显示了低浓度奥沙西林的联合治疗可控制不同的实验室和高度多样化的临床MRSA菌株。