Overview Methicillin-Resistant Staphylococcus Aureus Combination Treatment Options in Vivo and in Vitro

The spread of multidrug-resistant Staphylococcus aureus continues to threaten global health. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the common causes of bacterial infections in hospitals and communities. Despite vancomycin being an effective treatment for MRSA, from 2006 to 2020, vancomycin-resistant MRSA increased 3.5-fold, from 5% to 7%. Bacterial genome mutations, as well as bacteria’s ability to transfer genetic material with other bacteria, allowing them to obtain resistance genes from different strains, are all factors contributing to the development of vancomycin resistance in MRSA. As a result, combination therapy may be a potential treatment for MRSA infection. We searched in PubMed and Google Scholar, and our search yielded 92 articles, out of which 74 full-text articles were reviewed and 56 were selected for this study. This literature review examines combination therapies for MRSA infections, such as -Lactams with vancomycin, linezolid and imipenem, daptomycin and ceftaroline. The review yielded several studies looking at the synergy between -lactams and vancomycin. Although linezolid and rifampicin demonstrate synergy against MRSA in vivo and in vitro in various invasion diseases, more clinical research is required to prove their efficacy. Furthermore, daptomycin plus ceftaroline shows synergy for refractory staphylococcal bacteremia in vivo and in vitro. Combining ceftaroline and daptomycin has two benefits: they work synergistically together and make the innate host defense peptide cathelicidin leucine-leucine-37 (LL-37) more sensitizing. Ceftaroline plus daptomycin was recently used in MRSA biofilm infections, demonstrating a potentially promising treatment as the first combination used without side effects in humans. Keywords: Bacteremia, Vancomycin, Daptomycin, Ceftaroline, Staphylococcus aureus, MRSA.