Comparison On In-vitro Induction Of Resistance In Methicillin-resistance Staphyloccus Aureus To Vancomycin, Teicoplanin And Linezolid

Objective: Methicillin-resistant staphylococcus aureus (MRSA) infection has been increasing worldwide recently and is reagrded as one of the three refractory infectious diseases together with HBV and AIDS. The heterogeneity and multiple drug resistance of MRSA [1] are a kind of challenge to treatment. At present, the commonly used antibiotics are glycopeptides and oxazolidinones. The glycopeptides include vancomycin and teicoplanin and the oxazolidinones include linezolid. However, the domestic and overseas reports appear now and then about clinical isolates of vancomycin-intermediate Staptytococous aureus (VISA), heterogennous vancomycin-intermediate Staptytococcus aureus (h-VISA) and vancomycin-resistant Staptytococous aureus (VRSA). The MRSA resistant to linezolid has been reported abroad recently. It is believed that these antibiotic resistance are due to the selection condition which comes from the type of drugs. Some studies have been performed which used vancomycin to induce MRSA in vitro, and the results revealed that it was difficult to produce VRSA. It was also found that the minimal inhibitory concentration(MIC) of vancomycin to MRSA nevertheless increased, and part of the MRSA strains transfered to h-VISA strains [2-3]. This paper aims to explore the difference of vancomycin, teicoplanin and linezolid in the induction of MRSA by measuring MIC before and after drug administration.Methods: We isolated 20 staphylococcus stains from blood, phlegm, secretion specimens of patients in the second affiliated hospital of Dalian Medical University between August 2010 and October 2010. Nine strains of staphylococcus (S. aureus) were identified by API-Staph system. MICs of these S. aureus to oxacillin, vancomycin, teicoplanin and linezolid were determined by two-fold agar dilution method and 2 MRSA strains were aquired. Inducing resistance [2-5]: the MH agar plates containing vancomycin, teicoplanin and linezolid were prepared respectively according to MRSA's 1/2 MIC. There were colonies growth after incubating MRSA in the MH agar plates for 24 hours at 37°C. Several colonies were randomly selected form MH agar plates to passage onto the plates containing drugs. This procedure was repeated daily for 25 days. Similarly, strains were cultured in the MH agar plates without drugs for 25 days. During the procedure, the 5th, 10th, 15th, 20th and 25th generations of passaged strains were reserved and MIC to vancomycin, teicoplanin and linezolid were detected by two-fold agar dilution method.Results: After vancomycin, teicoplanin and linezolid inducing MRSA for 25 generations respectively, the MIC of vancomycin and linezolid increased 2 times and teicoplanin increased 2.67 times compared with those before drug induction. However, there was no difference of the change of MIC among the 3 groups. Additionally, no resistant strains were generated. The MIC of 3 drugs to MRSA strains in control groups in drug-free plates did not change after passage.Conclusions: No vancomycin, teicoplanin and linezolid resistant MRAS strains are found after drug inducing passage for 25 generations. There are no significant difference in the change of MIC and no resistant strains are generated among 3 groups.