Novel Compound AMC20 synergism Amoxicillin against Methicillin Resistance Staphylococcus Aureus- MRSA

Abstract

Abstract The World Health Organization has categorized methicillin-resistant Staphylococcus aureus (MRSA) as one of the bacteria which are posing greater challenges to the healthcare systems and disease management. Given the resistance to nearly all β-lactam antibiotics, there is need of alternative options including the antibiotics combination therapy for treating MRSA infections. This study was designed to determine in vitro and in vivo efficacy of the combination of amoxicillin and compound AMC20 against MRSA. Both amoxicillin and AMC20 were tested, as monotherapy and in combination, against six MRSA strains (four HA-MRSA, a CA-MRSA, and an LA-MRSA) in minimum inhibitory concentration (MIC) assay, Fractional Inhibitory Concentration (FIC) assay, time kill assay, and minimum biofilm inhibitory assay. The survival rates in MRSA infected Galleria mellonella larvae model was also determined. The MIC of single treatment AMC20 against the MRSA strains was found to be 128–512 µg/mL, and MIC of amoxicillin tratment was found as 256 – 2048 µg/mL. In the checkerboard assay, the FICI for all the six MRSA strains was ≤ 0.5 indicating synergism between the two compounds. In the time kill assay, the combination inhibited the MRSA growth by ≤2 log10 in 24 hours, in contrast to individual compounds which inhibited for two hours only to 6 log10. The combination was also found to inhibit the formation of MRSA biofilm significantly compared with individual compounds (P<0.01). The survival rate for seven days in MRSA infected Galleria mellonella model was higher with the combination therapy, compared with the amoxicillin and AMC20 alone. Collectively, this study presents preliminary synergism of amoxicillin and AMC20 combination against the selected MRSA strains and give a good choice treatment for MRSA infection. This study needs replicate studies in higher animal models before clinical use.