Department of Clinical Laboratory Medicine, Second Affiliated Hospital of Zhejiang University, Hangzhou, China; Center for Cancer Biology and Innovative Therapeutics, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, China.
Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, China; State Key Lab of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China.
Lancet Infect Dis. 2018 Jan;18(1):37-46. doi: 10.1016/S1473-3099(17)30489-9. Epub 2017 Aug 29.
Hypervirulent Klebsiella pneumoniae strains often cause life-threatening community-acquired infections in young and healthy hosts, but are usually sensitive to antibiotics. In this study, we investigated a fatal outbreak of ventilator-associated pneumonia caused by a new emerging hypervirulent K pneumoniae strain.
The outbreak occurred in the integrated intensive care unit of a new branch of the Second Affiliated Hospital of Zhejiang University (Hangzhou, China). We collected 21 carbapenem-resistant K pneumoniae strains from five patients and characterised these strains for their antimicrobial susceptibility, multilocus sequence types, and genetic relatedness using VITEK-2 compact system, multilocus sequence typing, and whole genome sequencing. We selected one representative isolate from each patient to establish the virulence potential using a human neutrophil assay and Galleria mellonella model and to establish the genetic basis of their hypervirulence phenotype.
All five patients had undergone surgery for multiple trauma and subsequently received mechanical ventilation. The patients were aged 53-73 years and were admitted to the intensive care unit between late February and April, 2016. They all had severe pneumonia, carbapenem-resistant K pneumoniae infections, and poor responses to antibiotic treatment and died due to severe lung infection, multiorgan failure, or septic shock. All five representative carbapenem-resistant K pneumoniae strains belonged to the ST11 type, which is the most prevalent carbapenem-resistant K pneumoniae type in China, and originated from the same clone. The strains were positive on the string test, had survival of about 80% after 1 h incubation in human neutrophils, and killed 100% of wax moth larvae (G mellonella) inoculated with 1 × 10 colony-forming units of the specimens within 24 h, suggesting that they were hypervirulent K pneumoniae. Genomic analyses showed that the emergence of these ST11 carbapenem-resistant hypervirulent K pneumoniae strains was due to the acquisition of a roughly 170 kbp pLVPK-like virulence plasmid by classic ST11 carbapenem-resistant K pneumoniae strains. We also detected these strains in specimens collected in other regions of China.
The ST11 carbapenem-resistant hypervirulent K pneumoniae strains pose a substantial threat to human health because they are simultaneously hypervirulent, multidrug resistant, and highly transmissible. Control measures should be implemented to prevent further dissemination of such organisms in the hospital setting and the community.
Chinese National Key Basic Research and Development Program and Collaborative Research Fund of Hong Kong Research Grant Council.
产超广谱β-内酰胺酶（ESBL）肺炎克雷伯菌常引起年轻健康宿主的致命性社区获得性感染，但通常对抗生素敏感。在本研究中，我们调查了由一种新出现的产超广谱β-内酰胺酶肺炎克雷伯菌引起的致命性呼吸机相关性肺炎爆发。
该爆发发生在浙江大学第二附属医院（杭州）新分院的综合重症监护病房。我们从五名患者中收集了 21 株耐碳青霉烯类肺炎克雷伯菌，并使用 VITEK-2 紧凑型系统、多位点序列分型和全基因组测序对这些菌株的抗菌药物敏感性、多位点序列分型和遗传相关性进行了表征。我们从每位患者中选择一个代表分离株，用于通过人类中性粒细胞测定和大蜡螟模型建立其毒力潜力，并建立其超毒力表型的遗传基础。
所有五名患者均因多发创伤接受手术治疗，随后接受机械通气。患者年龄 53-73 岁，2016 年 2 月底至 4 月入住重症监护病房。他们均患有严重肺炎、耐碳青霉烯类肺炎克雷伯菌感染，对抗生素治疗反应不佳，并因严重肺部感染、多器官衰竭或感染性休克而死亡。所有五株耐碳青霉烯类肺炎克雷伯菌代表株均属于 ST11 型，该型是中国最常见的耐碳青霉烯类肺炎克雷伯菌，且源自同一克隆。这些菌株的串珠试验呈阳性，在人类中性粒细胞孵育 1 小时后存活率约为 80%，接种 1×10 个菌落形成单位的标本后，100%的蜡螟幼虫（大蜡螟）在 24 小时内死亡，表明它们是产超广谱β-内酰胺酶肺炎克雷伯菌。基因组分析表明，这些 ST11 耐碳青霉烯类超毒力肺炎克雷伯菌的出现是由于经典 ST11 耐碳青霉烯类肺炎克雷伯菌获得了大约 170 kbp 的 pLVPK 样毒力质粒。我们还在来自中国其他地区的标本中检测到这些菌株。
ST11 耐碳青霉烯类超毒力肺炎克雷伯菌对人类健康构成重大威胁，因为它们同时具有高毒力、多重耐药性和高度传染性。应采取控制措施，防止此类病原体在医院环境和社区中进一步传播。
中国国家重点基础研究发展计划和香港研究资助局协作研究基金。
