Gostev Vladimir, Sabinova Ksenia, Sopova Julia, Kalinogorskaya Olga, Sulian Ofeliia, Chulkova Polina, Velizhanina Maria, Pavlova Polina, Danilov Lavrentii, Kraeva Lyudmila, Polev Dmitrii, Martens Elvira, Sidorenko Sergey
Pediatric Research and Clinical Center for Infectious Diseases, Professor Popov Str. 9, Saint Petersburg, 197022, Russia.
North-Western State Medical University Named After I. I. Mechnikov, Piskarevskij Prospect 47, Saint Petersburg, 195067, Russia.
Eur J Clin Microbiol Infect Dis. 2023 Sep;42(9):1125-1133. doi: 10.1007/s10096-023-04646-1. Epub 2023 Jul 29.
The aim of this study is to describe the phenotypic and genetic properties of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) isolates and their beta-lactam resistant derivatives obtained after selection with oxacillin. A collection of hospital- (HA-) and community-acquired (CA-) MRSA was screened for oxacillin susceptibility. Antibiotic susceptibility testing, population analysis profile (PAP), mecA expression analysis, and whole genome sequencing (WGS) were performed for 60 mecA-positive OS-MRSA isolates. Twelve high-level beta-lactam resistant derivatives selected during PAP were also subjected to WGS. OS-MRSA were more prevalent among CA-MRSA (49/205, 24%) than among HA-MRSA (11/575, 2%). OS-MRSA isolates belonged to twelve sequence types (ST), with a predominance of ST22-t223-SCCmec IVc and ST59-t1950-SCCmec V lineages. OS-MRSA were characterized by mecA promoter mutations at - 33 (C→T) or - 7 (G→T/A) along with PBP2a substitutions (S225R or E246G). The basal and oxacillin-induced levels of mecA expression in OS-MRSA isolates were significantly lower than those in control ST8-HA-MRSA isolates. Most of the OS-MRSA isolates were heteroresistant to oxacillin. High-level beta-lactam resistant OS-MRSA derivatives selected with oxacillin carried mutations in mecA auxiliary factors: relA (metabolism of purines), tyrS, cysS (metabolism of tRNAs), aroK, cysE (metabolism of amino acids and glycolysis). Cefoxitin-based tests demonstrated high specificity for OS-MRSA detection. The highest positive predictive values (PPV > 0.95) were observed for broth microdilution, the VITEK® 2 automatic system, and chromogenic media. Susceptibility testing of CA-MRSA requires special attention due to the high prevalence of difficult-to-detect OS-MRSA among them. Mis-prescription of beta-lactams for the treatment of OS-MRSA may lead to selection of high-level resistance and treatment failures.
本研究的目的是描述对苯唑西林敏感的耐甲氧西林金黄色葡萄球菌（OS-MRSA）分离株及其经苯唑西林筛选后获得的β-内酰胺耐药衍生物的表型和遗传特性。对一批医院获得性（HA-）和社区获得性（CA-）MRSA进行苯唑西林敏感性筛选。对60株mecA阳性的OS-MRSA分离株进行了抗生素敏感性试验、群体分析图谱（PAP）、mecA表达分析和全基因组测序（WGS）。在PAP过程中选择的12株高水平β-内酰胺耐药衍生物也进行了WGS。OS-MRSA在CA-MRSA（49/205，24%）中比在HA-MRSA（11/575，2%）中更常见。OS-MRSA分离株属于12种序列类型（ST），以ST22-t223-SCCmec IVc和ST59-t1950-SCCmec V谱系为主。OS-MRSA的特征是mecA启动子在-33（C→T）或-7（G→T/A）处发生突变，同时伴有PBP2a替代（S225R或E246G）。OS-MRSA分离株中mecA的基础表达水平和苯唑西林诱导表达水平显著低于对照ST8-HA-MRSA分离株。大多数OS-MRSA分离株对苯唑西林呈异质性耐药。用苯唑西林选择的高水平β-内酰胺耐药OS-MRSA衍生物在mecA辅助因子中发生突变：relA（嘌呤代谢）、tyrS、cysS（tRNA代谢）、aroK、cysE（氨基酸代谢和糖酵解）。基于头孢西丁的试验对OS-MRSA检测具有高特异性。肉汤微量稀释法、VITEK® 2自动系统和显色培养基的阳性预测值最高（PPV>0.95）。由于CA-MRSA中难以检测的OS-MRSA患病率高，其敏感性试验需要特别关注。β-内酰胺类药物用于治疗OS-MRSA的处方错误可能导致高水平耐药的选择和治疗失败。
