State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, China.
Respiratory Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Cell Infect Microbiol. 2021 Nov 1;11:756782. doi: 10.3389/fcimb.2021.756782. eCollection 2021.
Recently, KPC-producing has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463.
Retrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a infection model.
Among the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% 33.3%, = 0.03). and virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS elements (IS-Tn-tnp-IS--IS-IS). Plasmid from various species presented core was franked by mobile genetic element IS and IS
In the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the and genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.
最近，产 KPC 的 在华东地区迅速出现并蔓延。在这里，我们描述了属于序列型（ST）463 的主要产 KPC 的 CRPA 引起的血流感染（BSI）的临床影响和特征。
对 2019 年至 2020 年期间华东某医院的 CRPA BSI 病例进行回顾性队列研究。评估临床特征、危险因素和全病程死亡率。所有 CRPA 分离株均进行全基因组测序、药敏试验和血清耐药试验。选择代表性分离株进行 感染模型中的毒力检测。
在 50 例 CRPA BSI 病例中，ST463 占优势（48.0%）。多变量分析发现，死亡结局的三个独立危险因素是：携带 KPC（OR 4.8；95%CI 1.0-23.7； 0.05）、Pitt 菌血症评分（OR 1.3；95%CI 1.0-1.6； 0.02）和基础血液病（OR 8.5；95%CI 1.6-46.4； 0.01）。ST 之间的基线临床变量没有统计学差异，但 ST463 病例的 28 天死亡率明显高于非 ST463 病例（66.7% 33.3%， = 0.03）。所有 ST463 分离株均同时携带 和 毒力基因，几乎所有 ST463 分离株均产生碳青霉烯耐药基因 ，明显高于非 ST463 组（95.8% 7.7%，P<0.001）。ST463 CRPA 分离株对抗假单胞菌头孢菌素、单环β-内酰胺类和氟喹诺酮类的耐药率也更高。ST463 CRPA 已被证实对幼虫模型具有更高的毒力。一株 ST463 CRPA 菌株的基因组显示， 基因是唯一位于 41,104bp 质粒 pZYPA01 上的耐药基因，该质粒位于由两个 IS 元件（IS-Tn-tnp-IS--IS-IS）侧翼的 7kb 复合转座子样元件上。来自不同物种的质粒由移动遗传元件 IS 和 IS 框定的核心 呈现
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