A Study Of HVISA (Heterogeneous Vancomycin-intermediate Resistant Staphylococcus Aureus) In China: Prevalence, Molecular Epidemiology And Case Control Study

Objectives:To determine the prevalence of hVISA and VISA in China as well as the sensitivity and specificity of different screening methods.To characterize microbiological and molecular epidemiological characteristics of hVISA.To determine the risk factors and infection attributable mortality associated with hVISA/VISA infections.Methods:A total of 1,012 isolates of MRSA were collected as 6 groups in China from 2002 to 2007.Among them,a subgroup of 200 MRSA isolates from blood was investigated for hVISA by two agar screening methods BHIT5(brain heart infusion containing teicoplanin 5μg/ml) or BHIV6(brain heart infusion containing vancomycin 6μg/ml),macroEtest method(MET) and modified population analysis profile-area under the curve(PAP-AUC). The subgroup of MRSA from non-blood specimens(n=812) were screened by a cascasde of BHIT5 and MET.The MICs of vancomycin,teicoplanin,daptomycin,linezolid,ceftobiprole as well as tigecycline were determined by agar dilution or microbroth dilution as recommended by CLSI.All 200 isolates from blood subset were classified by SCCmec typing and agr typing,and partially by spa typing.A retrospective case control study of patients with hVISA infection or VSSA infection was carried out and statistical analysis was performed using student's t test,Mann-Whitney test,x~2 test and fisher exact test.Results:In the blood subset(n=200),1 isolate of VISA(0.5%) and 26 isolates of hVISA (13.0%) were identified by PAP-AUC.The sensitivity and specificity of BHIT5 were 88.8% and 17.3%,respectively,while BHIV6 with 3.7%of sensitivity and 98.8%of specificity.The sensitivity and specificity of MET with cutoff value of≥8μg/ml for both vancomycin and teicoplanin or≥12μg/ml for teicoplanin were 70.4%and 48.0%,respectively.Limiting cutoff value to≥8μg/ml for both drugs improved the specificity to 85.0%.With this cutoff value,188 out of 1012 isolates were determined as hVISA.The overall prevalence of hVISA in China was estimated as 6.19%.All isolates except one were sensitive to vancomycin.The percentage of isolates with a vancomycin MIC≥1.0μg/ml in hVISA group was significantly higher than the percentage of VSSA group(81.8%versus 64.2%,p=0.002).All isolates were 100%sensitive to teicoplanin,daptomycin,linezolid,ceftobiprole and tigecycline.As for molecular epidemiology,the most frequent SCCmec and agr type in hVISA group were SCCmecⅢtype(70.4%) and agr1 type(66.7%),followed by SCCmecⅡtype(22.2%) and agr2 type(14.8%),without a significant difference with the VSSA group. We could not demonstrate a significant difference in infection attributable mortality between hVISA group and VSSA group.Conclusion:The prevalence of hVISA was relatively higher in China.The sensitivity and specificity varies among different screening methods.MET with cutoff value of≥8μg/ml for both vancomycin and teicoplanin has better specificity.Compared with VSSA, hVISA group has a higher average vancomycin MIC but still sensitive to many new antimicrobial agents such as daptomycin,linezolid,ceftobiprole and tigecycline.Prospective cohort study is necessary to reveal the correlation between hVISA and infection attributable mortality.