Holmes Natasha E, Turnidge John D, Munckhof Wendy J, Robinson J Owen, Korman Tony M, O'Sullivan Matthew V N, Anderson Tara L, Roberts Sally A, Warren Sanchia J C, Coombs Geoffrey W, Tan Hui-Leen, Gao Wei, Johnson Paul D R, Howden Benjamin P
Austin Centre for Infection Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia Department of Paediatrics, Pathology and Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
J Clin Microbiol. 2014 Sep;52(9):3384-93. doi: 10.1128/JCM.01320-14. Epub 2014 Jul 16.
An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.
万古霉素最低抑菌浓度（MIC）升高与金黄色葡萄球菌菌血症（SAB）患者预后不良相关，且在未接受万古霉素治疗的甲氧西林敏感金黄色葡萄球菌（MSSA）菌血症患者中也有报道。在此，我们使用DNA微阵列和表型分析，利用来自SAB患者多中心双边队列的血培养分离株，研究了遗传预测因子和辅助基因调节因子（agr）功能及其与万古霉素MIC升高的关系。特定的克隆复合体与万古霉素MIC升高（克隆复合体8 [CC8] [P < 0.001]）或降低（CC22 [P < 0.001]、CC88 [P < 0.001]和CC188 [P = 0.002]）相关。agr功能障碍（P = 0.014）或agr基因型II（P = 0.043）也与万古霉素MIC升高相关。特定的耐药和毒力基因也与万古霉素MIC升高有关，包括blaZ（P = 0.002）、sea（P < 0.001）、clfA（P < 0.001）、splA（P = 0.001）和精氨酸分解代谢移动元件（ACME）位点（P = 0.02）。这些数据表明，无论接受何种抗生素治疗，固有生物体特征可能解释了SAB患者万古霉素MIC升高与预后不良之间的联系。在未来研究试图确定治疗效果或临床结局时，应考虑克隆特异性。
