Data_Sheet_1_Resistance and virulence features of hypermucoviscous Klebsiella pneumoniae from bloodstream infections: Results of a nationwide Italian surveillance study.PDF

Among Enterobacterales, Klebsiella pneumoniae (Kp) is one of the major opportunistic pathogens causing hospital-acquired infections. The most problematic phenomenon linked to Kp is related to the dissemination of multi-drug resistant (MDR) clones producing carbapenem-hydrolyzing enzymes, representing a clinical and public health threat at a global scale. Over the past decades, high-risk MDR clones (e.g., ST512, ST307, ST101 producing blaKPC–type carbepenemases) have become endemic in several countries, including Italy. Concurrently, the spread of highly virulent Kp lineages (e.g., ST23, ST86) able to cause severe, community-acquired, pyogenic infections with metastatic dissemination in immunocompetent subjects has started to be documented. These clones, designated as hypervirulent Kp (hvKp), produce an extensive array of virulence factors and are highly virulent in previously validated animal models. While the prevalence and distribution of MDR Kp has been previously assessed at local and national level knowledge about dissemination of hvKp remains scarce. In this work, we studied the phenotypic and genotypic features of hypermucoviscous (HMV, as possible marker of increased virulence) Kp isolates from bloodstream infections (BSI), obtained in 2016–17 from 43 Italian Laboratories. Antimicrobial susceptibility testing, whole genome sequencing and the use of two animal models (G. mellonella and murine) were employed to characterize collected isolates. Over 1502 BSI recorded in the study period, a total of 19 Kp were selected for further investigation based on their HMV phenotype. Results showed that hvKp isolates (ST5, ST8, ST11, ST25) are circulating in Italy, although with a low prevalence and in absence of a clonal expansion; convergence of virulence (yersiniabactin and/or salmochelin, aerobactin, regulators of mucoid phenotype) and antimicrobial-resistance (extended-spectrum beta-lactamases) features was observed in some cases. Conventional MDR Kp clones (ST307, ST512) may exhibit an HMV phenotype, but with a low virulence potential in the animal models. To the best of our knowledge, this work represents the first systematic survey on HMV and hvKp in Italy, employing a functional characterization of collected isolates. Future surveillance programs are warranted to monitor the threatening convergence of virulence and resistance among MDR Kp and the spread of hvKp.

在肠杆菌科中，肺炎克雷伯菌（Kp）是导致医院获得性感染的主要机会性病原体之一。与Kp相关的最棘手现象是产生碳青霉烯酶的多药耐药（MDR）克隆的传播，这一现象在全球范围内构成了临床和公共卫生的威胁。在过去几十年中，高风险的MDR克隆（例如，ST512、ST307、ST101产生blaKPC型碳青霉烯酶）在包括意大利在内的多个国家成为地方性流行。同时，具有高度致病性的Kp谱系（例如，ST23、ST86）的传播，这些谱系能够引起严重的社区获得性化脓性感染，并在免疫正常个体中发生转移性播散，已经开始被记录。这些克隆被称为高度致病性Kp（hvKp），它们产生了一系列的致病因子，并在先前验证的动物模型中表现出高度致病性。尽管MDR Kp的流行率和分布已经在前瞻性研究中得到评估，但关于hvKp传播的知识仍然十分匮乏。在本研究中，我们研究了来自2016-17年43个意大利实验室获得的血液感染（BSI）中分离出的高粘性粘液性（HMV，可能是增加致病性的标志）Kp菌株的表型和基因型特征。我们采用了抗菌敏感性测试、全基因组测序以及两种动物模型（粉蛀虫和鼠）的使用，以表征收集到的分离株。在研究期间记录的超过1502例BSI中，根据其HMV表型，共选择了19株Kp进行进一步研究。结果显示，hvKp分离株（ST5、ST8、ST11、ST25）在意大利有传播，尽管其流行率较低，且没有克隆扩散；在某些病例中观察到致病性（耶尔森素和/或沙门素、aerobactin、粘液表型调节因子）和抗菌耐药性（广谱β-内酰胺酶）特征的趋同。传统的MDR Kp克隆（ST307、ST512）可能表现出HMV表型，但在动物模型中的致病潜力较低。据我们所知，这项工作代表了意大利对HMV和hvKp进行的首次系统性调查，采用了收集到的分离株的功能性表征。未来的监测计划有必要监控MDR Kp中致病性和耐药性的威胁性趋同以及hvKp的传播。