An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2-Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting.

An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2-Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting.
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DOI:
10.1093/cid/ciz1095
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发表时间:
2020-10-23
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Gales AC
Gales AC
中科院分区:
其他
文献类型:
--
作者:
Andrey DO;Pereira Dantas P;Martins WBS;Marques De Carvalho F;Almeida LGP;Sands K;Portal E;Sauser J;Cayô R;Nicolas MF;Vasconcelos ATR;Medeiros EA;Walsh TR;Gales AC

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产生碳青霉烯酶的肺炎克雷伯菌已成为全球优先事项,尤其是在低收入和中等收入国家。在这里,我们报告了一个新的肺炎克雷伯菌碳青霉烯酶产生型(KPC-KP)序列类型(ST)16克隆的出现和临床影响。在巴西一家教学医院,建立了一个成人KPC-KP血流感染(BSI)病例的回顾队列(2014年1月至2016年12月),以研究分子流行病学及其对预后的影响(30天全原因死亡)。对KPC-KP分离株进行多位点序列分型。对ST/CC组之间的生存分析和死亡结局的危险因素(Logistic回归)进行评估。代表性的分离株进行了全基因组测序,并在Galeria幼虫模型中测试了它们的毒力。已确定165例独特的KPC-KP BSI病例。细菌以CC258为主(66%),其次为ST16(12%)。总的30天死亡率为60%;相比之下,95%的ST16病例是致命的。患者的严重程度评分很高,基线临床变量在不同的STS中没有统计学差异。在多因素分析中,ST_(16)(优势比[OR],21.4;95%可信区间[CI],2.3~202.8;P=.008)和感染性休克(OR,11.9;95%CI,4.2~34.1;P<.001)是死亡结局的独立危险因素。ST16克隆携带多达14个抗性基因,包括IncFIBpQIL质粒中的blaKPC-2、KL51胶囊和yersiniabactin毒力决定因素。在幼虫模型中,ST16克隆具有较高的致病性。在KPC-KP BSI队列中,CC258是地方性疾病,死亡率很高。新出现的ST16克隆与高死亡率有关。我们的结果表明,即使在流行环境中,高毒力克隆也可能迅速出现,需要持续监测。一个新出现的克隆,肺炎克雷伯菌碳青霉烯酶2产生肺炎克雷伯菌ST16,与CC258流行环境中的高死亡率有关。该克隆携带KL51衣壳,在Galeria幼虫致病模型中表现出比CC258克隆更高的毒力。
Carbapenemase-producing Klebsiella pneumoniae has become a global priority, not least in low- and middle-income countries. Here, we report the emergence and clinical impact of a novel Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-KP) sequence type (ST) 16 clone in a clonal complex (CC) 258–endemic setting. In a teaching Brazilian hospital, a retrospective cohort of adult KPC-KP bloodstream infection (BSI) cases (January 2014 to December 2016) was established to study the molecular epidemiology and its impact on outcome (30-day all-cause mortality). KPC-KP isolates underwent multilocus sequence typing. Survival analysis between ST/CC groups and risk factors for fatal outcome (logistic regression) were evaluated. Representative isolates underwent whole-genome sequencing and had their virulence tested in a Galleria larvae model. One hundred sixty-five unique KPC-KP BSI cases were identified. CC258 was predominant (66%), followed by ST16 (12%). The overall 30-day mortality rate was 60%; in contrast, 95% of ST16 cases were fatal. Patients’ severity scores were high and baseline clinical variables were not statistically different across STs. In multivariate analysis, ST16 (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3–202.8; P = .008) and septic shock (OR, 11.9; 95% CI, 4.2–34.1; P < .001) were independent risk factors for fatal outcome. The ST16 clone carried up to 14 resistance genes, including blaKPC-2 in an IncFIBpQIL plasmid, KL51 capsule, and yersiniabactin virulence determinants. The ST16 clone was highly pathogenic in the larvae model. Mortality rates were high in this KPC-KP BSI cohort, where CC258 is endemic. An emerging ST16 clone was associated with high mortality. Our results suggest that even in endemic settings, highly virulent clones can rapidly emerge demanding constant monitoring. An emerging clone, Klebsiella pneumoniae carbapenemase 2–producing K. pneumoniae ST16, associated with high mortality rates in a CC258 endemic setting, was identified. This clone carried the KL51 capsule and displayed higher virulence in a Galleria larvae pathogenicity model than CC258 clones.
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