A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study.

BACKGROUND: 背景

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.

高毒力肺炎克雷白杆菌常常导致年轻人和健康人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，我们对一株新出现的高独立肺炎克雷白杆菌导致的呼吸机相关性肺炎暴发流行进行了研究。

METHODS: 方法

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.

暴发流行发生在浙江大学附属第二医院的综合ICU。我们收集了来自5名患者的21株耐碳青霉烯肺炎克雷白杆菌，并且采用VITEK-2集成系统，多位点序列分析及全基因组测序分析了其抗生素药敏，多位点序列分型，以及遗传相关性。我们从每名患者选择了一个有代表性的分离株，并采用人中性粒细胞分析和大蜡螟模型分析菌株毒力，并确定其高毒力表型的遗传学基础。

FINDINGS: 结果

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 × 10⁶ 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.

所有5名患者均因多发创伤接受手术治疗后使用机械通气。患者年龄53-73岁，于2016年2月至4月间入住ICU。患者均罹患严重肺炎，耐碳青霉烯肺炎克雷白杆菌感染，且对抗生素治疗反应不佳，最终因严重肺部感染、多器官功能衰竭或感染性休克死亡。全部5株代表性耐碳青霉烯肺炎克雷白杆菌菌株均为ST11型，即中国最常见的耐碳青霉烯肺炎克雷白杆菌，来源于同一克隆。菌株的string试验为阳性，与人中性粒细胞孵育1小时后约80%存活，接种1 × 10⁶ CFU时24小时内可杀灭100%的蜡螟幼虫，提示为高毒力肺炎克雷白杆菌。基因组分析显示，这些ST11耐碳青霉烯的高毒力肺炎克雷白杆菌菌株源于经典的ST11耐碳青霉烯肺炎克雷白杆菌获得了约170 kbp pLVPK样毒力质粒。我们还在中国其他地区收集的标本中检测到这些菌株。

INTERPRETATION: 结论

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.

ST11耐碳青霉烯高毒力肺炎克雷白杆菌同时具有高毒力、多重耐药及高度可传播性的特点，对人类健康造成很大威胁。应当采取控制措施以防止这一致病菌在医院内和社区的进一步播散。

FUNDING: 资助

Chinese National Key Basic Research and Development Program and Collaborative Research Fund of Hong Kong Research Grant Council.