Antibacterial effects of vancomycin in combination with methicillin against methicillin-resistant and methicillinsensitive Staphylococcus aureus

Staphylococcus aureus is considered as a frequent cause of infections. Therefore, antibacterial agents including β-lactam are normally used to treat these infections while the emergence of antibiotic resistance is one of the major clinical problems in this respect. Accordingly, combination antibacterial therapy is one way to alleviate this problem. As a result, the present study aimed to investigate the combined effects of vancomycin and methicillin on clinical isolates of methicillin-resistant S. aureus (MRSA) and methicillinsensitive S. aureus (MSSA). In addition, a series of follow-up studies were performed to evaluate the antibacterial activity. The current cross-sectional study was conducted on 40 hospitalized patients from various clinical samples such as pus/wound swabs, blood, urine and sputum during a 6-month period in 2017. To this end, the antibacterial activities of vancomycin and methicillin, alone and in combination were investigated against MRSA and MSSA. Eventually, the inhibitory effects of vancomycin and methicillin alone and in combination were studied on the growth profile of MRSA and MSSA, as well as the expression of mecA gene. Based on the results, the significant synergistic and partial synergistic activity with fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) indexes ranged from 0.27-0.938 and 0.313-0.844, respectively, in the combination of vancomycin and methicillin in MRSA and MSSA isolates. Further, the obtained data indicated that the combination of vancomycin and methicillin had a synergistic effect against MRSA isolates (P<0.01). The expression levels of the mecA gene were down-regulated by 5.25- fold in the combination of vancomycin and methicillin in MRSA isolate (P<0.001). In general, these events may reflect the potential uses of vancomycin and methicillin combination against MRSA. However, a greater understanding of the underlying molecular mechanisms of vancomycin and methicillin in combination could contribute to the development of therapeutic strategies.