Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study.
Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study.
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由肺炎克雷伯菌碳青霉烯酶引起的血流感染，产生铜绿假单胞菌序列类型 463，与中国的高死亡率相关：一项回顾性队列研究
DOI：
10.3389/fcimb.2021.756782
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发表时间：
2021
影响因子：
5.7
通讯作者：
Qu T
中科院分区：
文献类型：
--
作者：
Hu H;Zhang Y;Zhang P;Wang J;Yuan Q;Shi W;Zhang S;Feng H;Chen Y;Yu M;Chen H;Jiang Y;Yang Q;Qu T
近年来，产KPC的铜绿假单胞菌在华东地区迅速崛起并扩大。在这里，我们描述了来自属于序列类型（ST）463的优势产KPC CRPA的血流感染（BSI）的临床影响和特征。对华东某医院2019 - 2020年CRPA BSI病例进行回顾性队列研究。对临床特征、危险因素和全过程死亡率进行了评估。所有CRPA分离株均进行了全基因组测序、抗菌药物敏感性试验和血清耐药性测定。在大蜡螟感染模型中检测代表性分离株的毒力。在50例CRPA BSI病例中，ST 463占优势（48.0%）。在多变量分析中，我们发现致死性结局的三个独立危险因素：KPC携带（OR 4.8; CI 95% 1.0-23.7; P = 0.05）、Pitt菌血症评分（OR 1.3; CI 95% 1.0-1.6; P = 0.02）和基础血液学疾病（OR 8.5; CI 95% 1.6-46.4; P = 0.01）。不同ST组的基线临床变量无统计学差异，但ST 463病例的28天死亡率显著高于非ST 463病例（66.7% vs 33.3%，P = 0.03）。所有ST 463菌株均同时存在exoU和exoS毒力基因，且几乎所有ST 463菌株均产生碳青霉烯类耐药基因bla KPC，显著高于非ST 463菌株（95.8%vs7.7%，P<0.001）。ST 463 CRPA分离株对头孢类、单胞菌和氟喹诺酮类抗生素的耐药率也较高。ST 463 CRPA在幼虫模型中被证实具有超强毒力。对ST 463 CRPA株的基因组分析表明，bla KPC-2基因是唯一的抗性基因，位于41，104 bp的质粒pZYPA 01上，携带在一个7 kb的复合转座子样元件上，两侧是两个IS 26元件（IS 26-Tn 3-tnpA-ISKpn 27-bla KPC-2-ISKpn 6-IS 26）。来自不同物种的质粒呈现核心bla KPC-2，其被移动的遗传元件ISKpn 27和ISKpn 6标记。 在ST 463 CRPA BSI队列中，死亡率高于非ST 463 CRPA BSI队列。同时携带bla KPC和exoU/exoS基因的ST 463 CRPA克隆在华东地区出现并传播，可能成为临床上的新威胁。提示我国乃至全球应加强对新的高危克隆ST 463 CRPA的监测。
Recently, KPC-producing P. aeruginosa 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 Galleria mellonella 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; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 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% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 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 bla KPC-2 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 IS26 elements (IS26–Tn3-tnpA–ISKpn27–bla KPC-2–ISKpn6–IS26). Plasmid from various species presented core bla KPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. 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 bla KPC and exoU/exoS 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.
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