Combination Antimicrobial Chemotherapy Against Methicillin-Resistant Staphylococcus Aureus Infection

Methicillin resistant Staphylococcus aureus(MRSA)is a multidrug-resistant bacterium that can cause serious infection in human and animals.At present,against the clinical serious infection caused by MRSA,available effective treatment schemes and the antimicrobial monotherapy are limited.Many studies have proved that the combination therapy shows the potential of anti MRSA infection,but systematic combination of drugs needs further study.In this paper,the clinical MRSA strain and a standard strain were used to explore the interaction of 11 antibiotics representing different mechanisms.We aim to screen the synergistic combination to provide more treatment strategies for clinical infection.The sensitivity of 11 antimicrobial agents against MRSA ATCC 43300 and clinical strain#161402 was determined by microdilution method.The results showed that#161402 was resistant to oxacillin,rifampicin,levofloxacin,fosfomycin,gentamycin and clindamycin,but sensitive to vancomycin,tigecycline,daptomycin and linezolid.According to the determination of drug interaction using ATCC 43300,the potential synergistic drug combinations were:levofloxacin plus oxacillin,vancomycin plus oxacillin,vancomycin plus rifampin,gentamicin plus oxacillin,chloramphenicol plus oxacillin,and chloromycetin plus fosfomycin.Followed,the above six combinations were tested by in vitro dynamic killing curves.The results showed that vancomycin plus oxacillin and vancomycin plus rifampin had good antibacterial effect against both ATCC 43300 and#161402.In order to further confirm the antibacterial effect of vancomycin plus oxacillin and vancomycin plus rifampin in vivo,the model of mice thigh infection in immunodeficient was further established.Comparing mono-drug treatment with combination therapy in 24,it showed that vancomycin plus oxacillin,vancomycin+rifampin had significant antibacterial efficacy against MRS A infection.In conclusion,the combination of vancomycin plus oxacillin and vancomycin plus rifampicin show synergistic antibacterial effect on multiple resistant MRSA infection.