Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan

Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan
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DOI:
10.1128/aac.00174-20
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发表时间:
2020-05-01
影响因子:
4.9
通讯作者:
Chen, Liang
Chen, Liang
中科院分区:
医学2区
文献类型:
--
作者:
Lin, Yi-Tsung;Cheng, Yi-Hsiang;Chen, Liang

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高毒力肺炎克雷伯菌菌株是整个东亚地区肝脓肿的主要原因,这些菌株通常对抗生素敏感。最近,多药耐药和高致病性(MDR- hv)肺炎克雷伯菌菌株已经出现,这是由于高致病性菌株获得抗微生物药物耐药性决定因素或将毒力质粒转移到经典的MDR菌株中。在本研究中,我们对台湾地区由耐多药hv毒株引起的肺炎克雷伯菌肝脓肿(KPLA)的临床和微生物学特征进行了研究。回顾性分析2013年1月至2018年5月在台北退伍军人总医院发现的社区起病KPLA患者。确定了耐药机制、荚膜类型和序列类型。耐多药- hv菌株及其亲本抗菌素敏感菌株进一步进行了全基因组测序(WGS)和小鼠体内致死试验。从218例KPLA病例中鉴定出13株耐多药hv毒株。耐多药hv毒株与抗菌素敏感毒株的结果相似。所有耐多药- hv毒株均为携带毒力荚膜型的传统高毒克隆。主要的耐药机制是外排泵的过度表达和/或获得ESBL或AmpC β -内酰胺酶基因。WGS显示,由于ramR基因突变和获得携带shv -12的质粒,两个高毒菌株进化为MDR表型。与亲本毒株相比,这两种耐多药毒株都保持了较高的毒力。耐多药hv肺炎克雷伯菌在社区的传播引起了公众的重大关注,应采取措施防止这些菌株进一步获得碳青霉烯酶和其他耐药基因,以避免不可治愈的KPLA的发生。
Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobialsusceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC beta-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.