JMI Laboratories, North Liberty, IA 52317, USA.
J Antimicrob Chemother. 2012 Jun;67(6):1321-4. doi: 10.1093/jac/dks069. Epub 2012 Mar 7.
To characterize the mechanisms responsible for elevated MICs of ceftaroline for methicillin-resistant Staphylococcus aureus (MRSA).
During the 2008 Assessing Worldwide Antimicrobial Resistance Evaluation ('AWARE') surveillance programme, four S. aureus collected from separate patients in Athens, Greece, demonstrated ceftaroline MICs of 4 mg/L. These isolates were clonally related and one strain (13101) was selected for further characterization. Two strains (4981 and 4977) displaying ceftaroline MICs of 1 and 2 mg/L, respectively, were included for comparison. All strains originated from the same hospital. Penicillin-binding protein (PBP) affinities for ceftaroline and comparators were determined. Strains were typed by single-locus typing (i.e. spa typing), multilocus sequence typing ('MLST') and by multiple-locus variable-number tandem repeat fingerprinting (MLVF). The presence of Pantone-Valentine leucocidin and the staphylococcal cassette chromosome mec types was assessed. We also performed nucleotide sequencing of the mecA (encoding PBP2a) promoter and ribosomal binding site (rbs) regions and mecR1.
Ceftaroline demonstrated the highest PBP2a affinity with strain 4981 (ST5-MRSA-II) (IC(50) 0.06 mg/L; MIC 1 mg/L). Strains 4977 and 13101 (both ST239-MRSA-III) showed indistinguishable MLVF profiles. Ceftaroline PBP2a binding affinity in strains 4977 (IC(50) 0.25 mg/L; MIC 2 mg/L) and 13101 (IC(50) 1 mg/L; MIC 4 mg/L) was 4- and 16-fold lower than 4981, respectively. Strain 4981 contains a wild-type PBP2a, while strains 4977 and 13101 have N(146)K and E(150)K alterations in the non-penicillin-binding domain. Additionally, 13101 has one substitution (H(351)N) in the transpeptidase domain. Alterations in the mecR1, mecA promoter or rbs regions were not observed.
Increased ceftaroline MICs were associated with decreased PBP2a binding affinity and reflected alterations in PBP2a.
描述耐甲氧西林金黄色葡萄球菌（MRSA）中头孢洛林 MIC 升高的机制。
在 2008 年评估全球抗菌药物耐药性监测计划（'AWARE'）期间，从希腊雅典的四位不同患者中分离出的四株金黄色葡萄球菌表现出头孢洛林 MIC 值为 4mg/L。这些分离株具有克隆相关性，其中一株（13101）被选为进一步鉴定。选择了两株 MIC 值分别为 1 和 2mg/L 的菌株（4981 和 4977）进行比较。所有菌株均来自同一家医院。确定了头孢洛林和比较剂对青霉素结合蛋白（PBP）的亲和力。通过单基因座分型（即 spa 分型）、多位点序列分型（'MLST'）和多位点可变数串联重复指纹图谱（MLVF）对菌株进行分型。评估了潘通-瓦伦丁白细胞毒素和葡萄球菌盒染色体 mec 类型的存在。我们还对 mecA（编码 PBP2a）启动子和核糖体结合位点（rbs）区域以及 mecR1 进行了核苷酸测序。
头孢洛林与 ST5-MRSA-II 型 4981 株（IC（50）0.06mg/L；MIC 1mg/L）具有最高的 PBP2a 亲和力。4977 株和 13101 株（均为 ST239-MRSA-III）的 MLVF 图谱无法区分。4977 株（IC（50）0.25mg/L；MIC 2mg/L）和 13101 株（IC（50）1mg/L；MIC 4mg/L）的头孢洛林 PBP2a 结合亲和力分别比 4981 株低 4 倍和 16 倍。4981 株含有野生型 PBP2a，而 4977 株和 13101 株在非青霉素结合域中具有 N（146）K 和 E（150）K 改变。此外，13101 株在转肽酶结构域中有一个取代（H（351）N）。未观察到 mecR1、mecA 启动子或 rbs 区域的改变。
头孢洛林 MIC 升高与 PBP2a 结合亲和力降低有关，反映了 PBP2a 的改变。
