Dramatic destruction of methicillin-resistant Staphylococcus aureus infections with a simple combination of amoxicillin and light-activated methylene blue.

BACKGROUND: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). METHODS: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. RESULTS: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. CONCLUSIONS: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.