(Antibiotics Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA

Abstract

The spreading of multiple drug -resistance Staphylococcus aureus is continuing to threaten global health. Since the 1960s, Methicillin-resistant Staphylococcus aureus (MRSA) has remained one of the major causes of health care and communities associated infections. S. aureus becomes resistant to methicillin through acquiring mecA gene from coagulase-negative S. aureus. MRSA is acquired by a horizontal mecA gene that encodes a penicillin-binding protein (PBP2a). Despite PBP2a encoded by mecA being the primary determinant for beta-lactam resistance in MRSA, other genes (auxiliary factors) are required for the full phenotypic beta-lactam resistance in MRSA. Although vancomycin antibiotic is the gold treatment for MRSA, resistance to the last line of antibiotics is observed. The β-lactam resistance limited treatment options for invasion infection of MRSA. Further, there are many challenging for discovering new antibiotics for MRSA such as ongoing resistance and low attractive economy. As a result, combination therapy might be one of the alternative solutions to combat MRSA infection. This literature review aimed to review some of the combination therapy discovered against MRSA and to analyse what has been known and their limitations. The result showed that triple combination of meropenem-piperacillin-tazobactam displayed high synergy against MRSA in vivo and in vitro. This could be a promising solution to tackle MRSA. Although linezolid combined with rifampicin exhibited a synergy against MRSA in vivo and vitro on several invasion diseases, further study is required in clinical practice use in order to prove their effectiveness. Combination therapy shows a bactericidal that might be overcome the deficiencies of monotherapy. Moreover, daptomycin plus ceftaroline showed synergy for refractory staphylococcal bacteraemia in vivo and vitro with offering benefits of sensitisation to cathelicidin IL-37 derived as an innate response that can attenuate the pathogen. Recently, ceftaroline plus daptomycin have been used in 116 patients with biofilm infections of MRSA, showing a potentially promising treatment as the first combination applied without side effects on humans. This could be a new novel for relapsing and refractory of a staphylococcal device infection. Moreover β-lactam plus vancomycin demonstrated synergy in vitro studies, but they are lack of in-vivo experiment and have limited data. In spite of some papers studied the antibiotic combination therapy by using comprehensive methods, the lack of the mechanism and resistance assay was crucial against their conclusion. Finally, Combination therapy for MRSA might be a good solution, but the clinical data is limited to characterized.