USA300 methicillin-resistant Staphylococcus aureus in Stockholm, Sweden, from 2008 to 2016

Methicillin-resistant Staphylococcus aureus (MRSA) USA300 isolates have been recognized globally, not only in community but also in healthcare settings. USA300 isolates were initially resistant only to methicillin, but resistance to non-β-lactams has emerged with time. To evaluate the prevalence and antimicrobial susceptibility of USA300 isolates in Stockholm, we conducted a nine-year retrospective study. Of 5359 consecutive MRSA cases in Stockholm, isolates from 285 cases were USA300 strains according to the pulsed-field gel electrophoresis pattern. Of these cases, repeated isolates with altered antibiotic resistance patterns were observed in six individuals. Therefore, antimicrobial susceptibility testing was performed on totally 291 isolates. To study the phylogenetic relatedness of isolates in transmission events and genomic resistance traits, 35 isolates were further studied by whole genome sequencing (WGS). The incidence of MRSA was increased from 17.6 per 100,000 inhabitants in 2008 to 37.3 per 100,000 inhabitants in 2016, while the proportion of USA300 cases declined from 6.6% in 2008 to 2.6% in 2016. Among the USA300 isolates, 73.5% were community-associated, 21.3% healthcare-associated, and 5.2% had unknown acquisition. The highest resistance rate among non-β-lactams was found in erythromycin (86%), followed by fluoroquinolones (68–69%). 57% of the isolates were resistant to both erythromycin and fluoroquinolone. Simultaneous resistance to four non-β-lactam antibiotic classes was found in six isolates. Four isolates were susceptible to all non-β-lactam antibiotics. Ceftaroline, daptomycin, linezolid, mupirocin, rifampicin, teicoplanin, telavancin, trimethoprim-sulfamethoxazole and vancomycin retained full activity in the study. WGS analysis indicated that isolates from an outbreak were phylogenetically closely related. In conclusion, USA300 MRSA isolates in Stockholm have neither been limited to the community setting, nor remained susceptible to non-β-lactam agents. WGS is becoming a useful tool in tracing transmission events. The results herein provide the most up-to-date and comprehensive information regarding status of USA300 strains in this geographic area.耐甲氧西林金黄色葡萄球菌（Methicillin-resistant Staphylococcus aureus, MRSA）USA300型分离株已在全球范围内被检出，不仅分布于社区环境，也可见于医疗场所。该型分离株最初仅对甲氧西林耐药，但随着时间推移，对非β-内酰胺类抗菌药物的耐药性逐渐显现。为评估斯德哥尔摩地区USA300型分离株的流行率与抗菌药物敏感性，本研究开展了一项为期九年的回顾性研究。在斯德哥尔摩地区的5359例连续性MRSA感染病例中，经脉冲场凝胶电泳（pulsed-field gel electrophoresis, PFGE）分型确认，285例的分离株为USA300型菌株。在上述病例中，6名患者检出了耐药谱发生改变的重复分离株，因此本研究共对291株分离株开展了抗菌药物敏感性试验。为探究传播事件中分离株的系统发育相关性及基因组耐药特征，本研究对其中35株分离株进行了全基因组测序（whole genome sequencing, WGS）。 MRSA的发病率从2008年的17.6/10万居民升至2016年的37.3/10万居民，而USA300阳性病例的占比则从2008年的6.6%降至2016年的2.6%。在USA300型分离株中，73.5%为社区获得性感染，21.3%为医疗相关获得性感染，剩余5.2%的感染途径未知。非β-内酰胺类抗菌药物中，红霉素的耐药率最高（86%），其次为氟喹诺酮类（68%~69%）；57%的分离株同时对红霉素和氟喹诺酮类耐药。另有6株分离株同时对四类非β-内酰胺类抗菌药物耐药，4株分离株对所有非β-内酰胺类抗菌药物均敏感。本研究中，头孢洛林、达托霉素、利奈唑胺、莫匹罗星、利福平、替考拉宁、特拉万星、甲氧苄啶-磺胺甲噁唑及万古霉素均保持了完整的抗菌活性。全基因组测序分析显示，某次暴发事件中的分离株具有高度相近的系统发育关系。 综上，斯德哥尔摩地区的USA300型MRSA分离株既未局限于社区传播环境，也未保留对非β-内酰胺类抗菌药物的敏感性。全基因组测序正成为追踪传播事件的有效工具。本研究结果为该地理区域内USA300菌株的流行现状提供了最新且全面的参考数据。