Respiratory Disease Branch, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
ASRT Inc., Contractor to Respiratory Diseases Branch, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0080222. doi: 10.1128/aac.00802-22. Epub 2022 Aug 15.
All known group A streptococci [GAS] are susceptible to β-lactam antibiotics. We recently identified an invasive GAS (iGAS) variant (/PBP2x-T553K) with unusually high minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin, although clinically susceptible to β-lactams. We aimed to quantitate PBP2x variants, small changes in β-lactam MICs, and lineages within contemporary population-based iGAS. PBP2x substitutions were comprehensively identified among 13,727 iGAS recovered during 2015-2021, in the USA. Isolates were subjected to antimicrobial susceptibility testing employing low range agar diffusion and PBP2x variants were subjected to phylogenetic analyses. Fifty-five variants were defined based upon substitutions within an assigned PBP2x transpeptidase domain. Twenty-nine of these variants, representing 338/13,727 (2.5%) isolates and 16 types, exhibited slightly elevated β-lactam MICs, none of which were above clinical breakpoints. The /PBP2x-T553K variant, comprised of two isolates, displayed the most significant phenotype (ampicillin MIC 0.25 μg/ml) and harbored missense mutations within 3 non-PBP genes with known involvement in antibiotic efflux, membrane insertion of PBP2x, and peptidoglycan remodeling. The proportion of all PBP2x variants with elevated MICs remained stable throughout 2015-2021 (<3.0%). The predominant lineage (/PBP2x-M593T/) was resistant to macrolides/lincosamides and comprised 129/340 (37.9%) of isolates with elevated β-lactam MICs. Continuing β-lactam selective pressure is likely to have selected PBP2x variants that had escaped scrutiny due to MICs that remain below clinical cutoffs. Higher MICs exhibited by /PBP2x-T553K are probably rare due to the requirement of additional mutations. Although elevated β-lactam MICs remain uncommon, /PBP2x-T553K and /PBP2x-M593T/ lineages indicate that antibiotic stewardship and strain monitoring is necessary.
所有已知的 A 组链球菌[GAS]均对β-内酰胺类抗生素敏感。我们最近发现了一种具有侵袭性的 GAS（iGAS）变体（/PBP2x-T553K），其氨苄西林和阿莫西林的最低抑菌浓度（MIC）异常高，尽管临床上对β-内酰胺类药物敏感。我们旨在定量研究 PBP2x 变体、β-内酰胺 MIC 的微小变化以及当代基于人群的 iGAS 中的谱系。在美国，2015-2021 年间共从 13727 例 iGAS 中全面鉴定了 PBP2x 取代物。对分离株进行了低范围琼脂扩散的抗菌药物敏感性测试，对 PBP2x 变体进行了系统发育分析。根据指定的 PBP2x 转肽酶结构域内的取代物，定义了 55 种变体。其中 29 种变体，代表 338/13727（2.5%）分离株和 16 种类型，表现出略微升高的β-内酰胺 MIC，均未超过临床折点。/PBP2x-T553K 变体由 2 株分离物组成，表现出最显著的表型（氨苄西林 MIC 0.25 μg/ml），并且在已知参与抗生素外排、PBP2x 膜插入和肽聚糖重塑的 3 个非 PBP 基因中存在错义突变。2015-2021 年间，所有具有升高 MIC 的 PBP2x 变体的比例保持稳定（<3.0%）。优势谱系（/PBP2x-M593T/）对大环内酯类/林可酰胺类药物耐药，占 340/13727（37.9%）具有升高β-内酰胺 MIC 的分离株。持续的β-内酰胺选择性压力可能选择了由于 MIC 仍低于临床截止值而未被发现的 PBP2x 变体。由于需要额外的突变，/PBP2x-T553K 表现出的更高 MIC 可能较为罕见。尽管升高的β-内酰胺 MIC 仍然不常见，但/PBP2x-T553K 和 /PBP2x-M593T/谱系表明需要进行抗生素管理和菌株监测。
