Andrey D O, François P, Manzano C, Bonetti E J, Harbarth S, Schrenzel J, Kelley W L, Renzoni A
Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.
Genomic Research Laboratory, Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.
Eur J Clin Microbiol Infect Dis. 2017 Feb;36(2):343-350. doi: 10.1007/s10096-016-2807-5. Epub 2016 Oct 15.
Ceftaroline is a broad-spectrum antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Ceftaroline susceptibility of an MRSA set archived between 1994 and 2003 in the Geneva University Hospitals detected a high percentage (66 %) of ceftaroline resistance in clonotypes ST228 and ST247 and correlated with mutations in PBP2a. The ceftaroline mechanism of action is based on the inhibition of PBP2a; thus, the identification of PBP2a mutations of recently circulating clonotypes in our institution was investigated. We analyzed ceftaroline susceptibility in MRSA isolates (2013 and 2014) and established that resistant strains correlated with PBP2a mutations and specific clonotypes. Ninety-six MRSA strains were analyzed from independent patients and were isolated from blood cultures (23 %), deep infections (38.5 %), and superficial (skin or wound) infections (38.5 %). This sample showed a ceftaroline minimum inhibitory concentration (MIC) range between 0.25 and 2 μg/ml and disk diameters ranging from 10 to 30 mm, with a majority of strains showing diameters ≥20 mm. Based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 76 % (73/96) of isolates showed susceptibility to ceftaroline. Nevertheless, we still observed 24 % (23/96) of resistant isolates (MIC = 2 μg/ml). All resistant isolates were assigned to clonotype ST228 and carried the N146K mutation in PBP2a. Only two ST228 isolates showed ceftaroline susceptibility. The decreasing percentage of ceftaroline-resistant isolates in our hospital can be explained by the decline of ST228 clonotype circulating in our hospital since 2008. We present evidence that ceftaroline is active against recent MRSA strains from our hospital; however, the presence of PBP2a variants in particular clonotypes may affect ceftaroline efficacy.
头孢洛林是一种对耐甲氧西林金黄色葡萄球菌（MRSA）菌株具有活性的广谱抗生素。对1994年至2003年在日内瓦大学医院存档的一组MRSA菌株进行的头孢洛林敏感性检测发现，克隆型ST228和ST247中头孢洛林耐药率很高（66%），且与PBP2a中的突变相关。头孢洛林的作用机制基于对PBP2a的抑制；因此，我们对本机构近期流行的克隆型的PBP2a突变进行了鉴定研究。我们分析了MRSA分离株（2013年和2014年）对头孢洛林的敏感性，确定耐药菌株与PBP2a突变和特定克隆型相关。对来自独立患者的96株MRSA菌株进行了分析，这些菌株分别从血培养（23%）、深部感染（38.5%）和浅表（皮肤或伤口）感染（38.5%）中分离得到。该样本显示头孢洛林的最低抑菌浓度（MIC）范围在0.25至2μg/ml之间，纸片直径在10至30mm之间，大多数菌株的直径≥20mm。根据欧洲抗菌药物敏感性试验委员会（EUCAST）的断点标准，76%（73/96）的分离株对头孢洛林敏感。然而，我们仍观察到24%（23/96）的耐药分离株（MIC = 2μg/ml）。所有耐药分离株均归为克隆型ST228，并在PBP2a中携带N146K突变。只有两株ST228分离株对头孢洛林敏感。我院头孢洛林耐药分离株比例的下降可归因于自2008年以来我院ST228克隆型的流行率下降。我们提供的证据表明，头孢洛林对我院近期的MRSA菌株具有活性；然而，特定克隆型中PBP2a变体的存在可能会影响头孢洛林的疗效。
