Genomic epidemiology and characterisation of penicillin-sensitive <i>Staphylococcus aureus</i> isolates from invasive bloodstream infections in China: an increasing prevalence and higher diversity in genetic typing be revealed

Many countries have reported increasing rates of penicillin-susceptible methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA-PEN^S). To date, there is relatively little known about the current situation and molecular characteristics of MSSA-PEN^S in China. In this study, we carried out a laboratory-based multi-region retrospective study to investigate the genomic epidemiology and characterisation of MSSA-PEN^S isolated from invasive bloodstream infections (BSIs) across 17 provinces. The prevalence of MSSA-PEN^S isolates increased significantly over the 6-year period, with the proportion increasing from 3.51% in 2014–8.80% in 2019, an average relative increase of 22.14% per year (95% confidence interval 9.67%-34.61%, P for trend &lt;0.001), suggesting that China is experiencing a resurgence of MSSA-PEN^S. Phylogenetic analysis showed a higher strain diversity occurred; the most frequent clonal complexes (CCs) identified were CC188 (17.14%), CC398 (15.71%) and CC5 (15.71%). Over half of MSSA-PEN^S strains were pan-susceptible, with erythromycin the most frequent resistance observed. Moreover, 25 isolates were identified as immune evasion cluster negative, including CC15, CC188 and CC1, and 6 strains encoded the Panton-Valentine leucocidin gene. Importantly, virulence assays showed that MSSA-PEN^S exhibited a level of virulence comparable to that of penicillin-resistant MSSA (MSSA-PEN^R), indicating that more-sensitive strains should not be mistaken for lacking aggressiveness in <i>vivo</i>. Furthermore, 11 of these isolates were confirmed as <i>blaZ</i> positive but phenotype sensitive, with different amino acid changes in <i>blaZ</i>. Our data support the recommendation to clinicians regarding the usage of penicillin in invasive BSIs caused by MSSA-PEN^S, which might create a novel opportunity for better antimicrobial stewardship in the future.

多国已有报道称，青霉素敏感型甲氧西林敏感金黄色葡萄球菌（*Staphylococcus aureus*, MSSA-PEN^S）的检出率呈上升趋势。迄今为止，国内关于MSSA-PEN^S的流行现状与分子特征的相关研究仍相对匮乏。本研究开展了一项基于实验室的多区域回顾性研究，旨在分析全国17个省份分离自侵入性血流感染（BSIs）的MSSA-PEN^S菌株的基因组流行病学特征及菌株分型情况。在6年的研究周期内，MSSA-PEN^S分离株的检出率显著上升，占比从2014年的3.51%升至2019年的8.80%，年均相对增幅达22.14%（95%置信区间：9.67%~34.61%，趋势检验P<0.001），提示我国MSSA-PEN^S感染正呈现复燃态势。系统发育分析显示菌株多样性较高；检出频率最高的克隆复合体（clonal complexes, CCs）依次为CC188（17.14%）、CC398（15.71%）与CC5（15.71%）。超过半数的MSSA-PEN^S菌株为全敏感株，最常见的耐药表型为红霉素耐药。此外，共有25株分离株被鉴定为免疫逃逸簇（immune evasion cluster, IEC）阴性，涵盖CC15、CC188与CC1等克隆型；另有6株携带潘顿-瓦伦丁杀白细胞素（Panton-Valentine leucocidin, PVL）编码基因。值得注意的是，毒力试验结果显示，MSSA-PEN^S的毒力水平与青霉素耐药型甲氧西林敏感金黄色葡萄球菌（MSSA-PEN^R）相当，提示临床不应将敏感株误认为在体内缺乏侵袭能力。进一步研究发现，11株分离株经证实为blaZ基因阳性但表型敏感，其blaZ基因存在不同的氨基酸突变。本研究数据可为临床医师针对MSSA-PEN^S所致侵入性血流感染使用青霉素类药物提供参考依据，有望为未来优化抗菌药物管理带来新的契机。