Background Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections. Methods Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016-2018 with cultures positive for carbapenemase-producing Enterobacter spp. were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed. Results We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp. from 30 hospitals in 7 countries. Among the 136 isolates, eleven Enterobacter species were identified, with most isolates belonging to E. xiangfangensis (n=81, 60%) and E. hoffmannii (n=17, 13%), and carrying blaKPC (n=106, 78%) and blaNDM (n=12, 9%). Clinical characteristics and outcomes were similar among patients with E. xiangfangensis, E. hoffmannii or the other Enterobacter spp. 30-day mortality was 20% and older age at enrollment (adjusted odds ratio 1.42, 95% confidence interval 1.08-1.87) was associated with increased mortality. Sequence type (ST)171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination. Conclusions Our findings demonstrated that E. xiangfangensis and E. hoffmannii are common species among international carbapenemase-producing Enterobacter spp., potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.

中文翻译：

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来自国际队列的产碳青霉烯酶肠杆菌属的分子流行病学和临床特征


背景 尽管耐碳青霉烯类肠杆菌属对全球公共卫生构成威胁，但对国际分离株的临床和分子流行病学研究仍然很少。从历史上看，肠杆菌的分类学一直具有挑战性，限制了我们对产生碳青霉烯酶的肠杆菌属感染的临床特征和结果的理解。方法 纳入 2016-2018 年参加 CRACKLE-2 研究 （ClinicalTrials.gov， NCT03646227） 且产碳青霉烯酶肠杆菌属培养阳性的住院患者。从健康记录中收集临床和微生物学数据。进行全基因组测序，并分析所选优势克隆的种群结构。结果 我们招募了来自 7 个国家 30 家医院的 136 例产碳青霉烯酶肠杆菌属住院患者。在 136 株分离株中，共鉴定出 11 种肠杆菌属，其中大多数分离株属于香方肠杆菌 （n=81， 60%） 和霍夫曼肠杆菌 （n=17， 13%），携带 blaKPC （n=106， 78%） 和 blaNDM （n=12， 9%）。香方肠球菌、霍夫曼肠球菌或其他肠杆菌属患者的临床特征和结局相似。30 天死亡率为 20%，入组年龄较大 （校正比值比 1.42,95% 置信区间 1.08-1.87） 与死亡率增加相关。序列类型 （ST）171 E. xiangfangensis、ST78 E. hoffmannii 和 ST93 E. xiangfangensis 是优势克隆，氟喹诺酮类药物耐药相关突变和碳青霉烯酶编码质粒的获得有助于其形成和全球传播。结论 我们的研究结果表明，E. xiangfangensis 和 E. 霍夫曼氏菌是国际上产碳青霉烯酶肠杆菌属的常见物种，可能与获得氟喹诺酮类药物耐药性和碳青霉烯酶编码质粒的一些主要克隆的克隆克隆的克隆传播有关。