Strommenger Birgit, Layer Franziska, Klare Ingo, Werner Guido
National Reference Centre for Staphylococci and Enterococci, Robert Koch Institute, Wernigerode Branch, Wernigerode, Germany.
PLoS One. 2015 May 8;10(5):e0125864. doi: 10.1371/journal.pone.0125864. eCollection 2015.
Ceftaroline is a new cephalosporin active against Methicillin-resistant Staphylococcus aureus (MRSA). Based on a representative collection of clinical S. aureus isolates from Germany, supplemented with isolates of clonal lineages ST228 and ST239, we demonstrate the in-vitro susceptibility towards ceftaroline prior to its introduction into clinical use for a total of 219 isolates. Susceptibility testing was performed by broth microdilution, disc diffusion and Etest, respectively. Results were interpreted according to EUCAST guidelines and showed considerable variance in dependence on clonal affiliation of the isolates tested. Among isolates of widespread hospital-associated lineages we found a high proportion of clinical isolates with MICs close to the EUCAST breakpoint (MIC50/90 1.0/1.5 mg/L); currently, interpretation of these "borderline" MICs is complicated by a lack of concordant susceptibility testing methods and reasonable breakpoint determination. Isolates of clonal lineages ST228 and ST239 demonstrated increased MIC50/90 values of 2.5/3.33 mg/L. Sequencing of mecA revealed no association of resistance to a specific mecA polymorphism, but rather reveals two regions in the non-penicillin-binding domain of PbP2a which displayed different combinations of mutations putatively involved in resistance development. This study provides national baseline data to (i) adjust susceptibility testing methods and current breakpoints to clinical and epidemiological requirements, (ii) evaluate current breakpoints with respect to therapeutic outcome and (iii) monitor further resistance evolution.
头孢洛林是一种对耐甲氧西林金黄色葡萄球菌（MRSA）有效的新型头孢菌素。基于从德国收集的具有代表性的临床金黄色葡萄球菌分离株，并补充了克隆谱系ST228和ST239的分离株，我们对总共219株分离株在引入临床使用前对头孢洛林的体外敏感性进行了研究。分别通过肉汤微量稀释法、纸片扩散法和Etest进行药敏试验。结果根据欧洲药敏试验委员会（EUCAST）指南进行解释，结果显示，所测试分离株的敏感性在很大程度上取决于所测试分离株的克隆谱系。在广泛的医院相关谱系的分离株中，我们发现有很大比例的临床分离株的最低抑菌浓度（MIC）接近EUCAST的折点（MIC50/90为1.0/1.5mg/L）；目前，由于缺乏一致的药敏试验方法和合理的折点确定，对这些“临界”MIC的解释很复杂。克隆谱系ST228和ST239的分离株显示MIC50/90值升高，分别为2.5/3.33mg/L。mecA基因测序显示，耐药性与特定的mecA多态性无关，而是揭示了青霉素结合蛋白2a（PbP2a）非青霉素结合域中的两个区域，这些区域显示出与耐药性发展可能相关的不同突变组合。本研究提供了国家基线数据，以（i）根据临床和流行病学要求调整药敏试验方法和当前折点，（ii）根据治疗结果评估当前折点，以及（iii）监测进一步的耐药性演变。
