Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA.
J Photochem Photobiol B. 2022 Oct;235:112563. doi: 10.1016/j.jphotobiol.2022.112563. Epub 2022 Sep 6.
Staphylococcus aureus is and continues to be a leading cause of bacterial infections throughout the world. Given the global dissemination of multi-drug resistant (MDR) S. aureus, particularly methicillin-resistant S. aureus (MRSA), novel solutions against S. aureus infections are urgently needed. In our study on the interactions between commonly used photosensitizers and antibiotics in the clinic, we discovered that MRSA can be dramatically destroyed by a simple combination of amoxicillin and light-activated methylene blue (MB).
To guide the clinical application of this combination therapy, we quantitatively assessed the interaction between light-activated MB and amoxicillin against S. aureus and its treatment order, dosage, and time length dependence. Furthermore, we evaluated the efficacy of this combination therapy in treating and halting the progression of MRSA infections with the catheter biofilm infection model and the pig skin burn infection model. In the end, we disclosed the antimicrobial mechanisms of this combination therapy to further facilitate its clinical translation.
Amoxicillin and light-activated MB can mutually boost each other's uptake in S. aureus, producing up to 8 logs of reduction of MRSA infections when they are co-administrated. Such an anti-S. aureus synergy could be triggered with the currently used MB and amoxicillin clinical administration regimens. It is effective against S. aureus pathogens regardless of their antibiotic resistance backgrounds and does not create significant bacterial resistance with five days of continuous applications. It can lead to more than 99% of reduction of S. aureus infections established not only on the medical devices but also on the body surfaces.
Possessing a fusion of effectiveness, safety, sustainability, and broad applicability, this simple combination of light-activated MB and amoxicillin can ultimately reform our treatment against MDR S. aureus pathogens including MRSA, significantly alleviating the health and economic burden of S. aureus infections across the world.
金黄色葡萄球菌一直是全球细菌性感染的主要病原体。鉴于全球耐多药（MDR）金黄色葡萄球菌，特别是耐甲氧西林金黄色葡萄球菌（MRSA）的传播，迫切需要针对金黄色葡萄球菌感染的新解决方案。在我们关于临床常用光敏剂与抗生素相互作用的研究中，我们发现，简单地将阿莫西林与光活化亚甲蓝（MB）联合使用，就可以显著破坏 MRSA。
为了指导这种组合疗法的临床应用，我们定量评估了光活化 MB 与阿莫西林对金黄色葡萄球菌的相互作用及其治疗顺序、剂量和时间依赖性。此外，我们还评估了这种组合疗法在导管生物膜感染模型和猪皮烧伤感染模型中治疗和阻止 MRSA 感染进展的疗效。最后，我们揭示了这种组合疗法的抗菌机制，以进一步促进其临床转化。
阿莫西林和光活化 MB 可以相互促进彼此在金黄色葡萄球菌中的摄取，当两者联合使用时，MRSA 感染的减少量高达 8 个对数级。这种抗金黄色葡萄球菌协同作用可以通过目前使用的 MB 和阿莫西林临床给药方案来触发。它对金黄色葡萄球菌病原体有效，无论其抗生素耐药背景如何，并且在连续应用五天后不会产生显著的细菌耐药性。它可以导致 99%以上的金黄色葡萄球菌感染减少，不仅在医疗器械上，而且在身体表面上。
这种简单的光活化 MB 和阿莫西林组合具有有效性、安全性、可持续性和广泛适用性，可以最终改变我们对抗包括 MRSA 在内的 MDR 金黄色葡萄球菌病原体的治疗方法，显著减轻全球金黄色葡萄球菌感染的健康和经济负担。
