Comparative Study Of Bactericidal Activity Of Linezolid And Vancomycin Agents Against Methicillin-resistant Staphylococcus Aureus

Objective：(1) To evaluate the in vitro antimicrobial activities of linezolid andvancomycin agents against methicillin-resistant Staphylococcus aureus (MRSA), andunderstand the two drug’s time-killing curves characteristics.(2) To investigate thepost-antibiotic effect(PAE) of linezolid and vancomycin against methicillin-resistantstaphyloccus aureus(MRSA), and observe morphological change of MRSA during thetwo drugs’ PAE.(3) To evaluated the in vitro antimicrobial activities and serumbactericidal activities of linezolid agents against Methicillin-resistant Staphylococcusaureus (MRSA) and Vancomycin-resistant Enterococci(VRE).Methods：(1) The minimal inhibitory concentrations (MICs) of antibacterial agentswere determined by the standard two-fold agar dilution method. The minimalbactericidal concentrations (MBCs) antibacterial agents were determined by tubebroth dilution method and time-killing curves were obtained.(2) Determined PAE oflinezolid and vancomycin against MRSA by plate colony counting in differentconcentrations and different time points, the culture medium were fixed with2%formaldehyde, using scanning electron microscopy morphological observedmorphological change of MRSA during the two drugs’ PAE.(3) The minimalinhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs)were measured by the standardized microdilution method. Serum bactericidal activityagainst clinical isolates of MRSA and VRE was measured by the standardizedmicrodilution method.Results：(1)The sensitive rates of linezolid and vancomycin against MRSA were both100%,the MIC50and MIC90were1μg. mL-1,1μg. mL-1and2μg. mL-1,1μg. mL-1respectively; the MBC50and MBC90were both8μg. mL-1,32μg. mL-1. With theincrease of drug concentrations, the killing time did not show obvious decline.(2)Linezolid and vancomycin against MRSA can produce significant PAE, and with the gradual extension of exposure time, showing a significant time-dependent.Compared with the control group, the two drugs’ morphological change of MRSAwas not observed during the two drugs’ PAE.(3) The ranges of MIC and MBC tolinezolid against8strains MRSA were0.5～1μg. mL-1,2～4μg. mL-1, respectively;the MIC90was1μg. mL-1, the MBC90was4μg. mL-1. The ranges of MIC and MBCto linezolid against8strains VRE were0.5μg. mL-1,1～4μg. mL-1, respectively; theMIC90was0.5μg. mL-1, the MBC90was4μg. mL-1. The peak concentrationpercentage of SBA≥1:8to linezolid against8strains MRSA were43.75%,41.67%and39.58%, respectively. The valley concentration percentage of SBA≥1:1to linezolid against8strains MRSA were25.00%,28.13%and31.25%, respectively.The peak concentration percentage of SBA≥1:8to linezolid against8strains VREwere47.91%,44.79%and41.67%, respectively. The valley concentration percentageof SBA≥1:1to linezolid against8strains VRE were27.08%,30.21%and32.29%,respectively.Conclusions：(1)Linezolid and vancomycin have strong antibacterial activity againstMRSA, the two drugs against MRSA have good bactericidal activity, and they havenon-concentration independent characteristic by the results of time-killing curves.(2)Linezolid and vancomycin can both produce significant PAE, and with the contacttime gradually extended, showing a significant time-dependent. Two drugs in thedesign clinical dosing regimen, the dosing interval may be reasonably extended. Afterinitial observation, linezolid and vancomycin during PAE, MRSA did not change theform, to be in-depth study.(3)The in vitro antibacterial activity of linezolid againstMRSA and VRE are similar to foreign reports, the peak concentration percentage ofSBA≥1:8with the gradual extension of the administration time decreased, while thevalley concentration percentage of SBA≥1:1with the gradual extension of thedelivery time increased. To hint three administration drug methods are effective tocure clinical infection caused by MRSA and VRE.