Combination therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections

Abstract

Staphylococcus aureus is an important human pathogen that causes wide range of infections such as bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections in nosocomial and community settings. Vancomycin has been used successfully to treat grampositive infections in clinical use for more than 50 year. However, there are major concerns due to increased resistance among S. aureus to this agent. Moreover, the increased understanding of vancomycin limitations has been an opportunity for the development of new agents. Combination antibiotics treatment for MRSA infections is an attractive alternative as it could address most of vancomycin’s shortcomings, including poor tissue penetration, slow bacterial killing, and emerging resistance in some strains of MRSA. However, the theoretical promise of combination therapy for MRSA infections has not been borne out in most in vitro and animal studies and clinical trials. This review comprehensively covers general introduction about bacteriology of S. aureus, emergence of MRSA, the epidemiology of MRSA, pathogenesis, clinical manifestations, biology of S. aureus (cell envelope and S. aureus genome), mechanism of MRSA resistance (β-lactam antibiotics resistance, mecA, Non-mecA, SCCmec element, auxiliary factors, current standard treatment for MRSA infections and their limitation , alternative approach to treat MRSA infections (combination therapy). In combination therapy section will focus more on β-lactam combination therapy for MRSA bacteraemia to review the efficacy and safety of this combination therapy with standard treatment for MRSA that are already widely used in clinical practice such as vancomycin, daptomycin, linezolid in vitro, in vivo animal models and in clinical trials. Other beneficial combination antibiotics which can contribute to treating persistent methicillin‐resistant Staphylococcus aureus infections will be mentioned. Finally, this review will conclude challenges of combination therapy and future research areas and conclusion