Luo Rongmu, Ma Guannan, Yu Qian, Tian Zhengqin, Man Qihang, Shu Xiangrong, Liu Xuetong, Shi Yupeng, Zhang Lei, Wang Jingbo
Department of Hematology, Aerospace Center Hospital, Beijing, China.
Department of Hematology, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, China.
Front Pediatr. 2025 Jan 6;12:1450201. doi: 10.3389/fped.2024.1450201. eCollection 2024.
Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses an increasing public health risk due to its high treatment difficulty and associated mortality, especially in bone marrow transplant (BMT) patients. The emergence of strains with multiple resistance mechanisms further complicates the management of these infections.
We isolated and characterized a novel ST11-KL64 hv-CRKP strain from a pediatric bone marrow transplantation patient. Antimicrobial susceptibility testing was performed to determine resistance patterns. Comprehensive genomic analysis was conducted to identify plasmid types, virulence factors, and antimicrobial resistance genes, as well as potential resistance mechanisms associated with mutations and plasmid-mediated variants.
The isolated hv-CRKP strain exhibited multidrug resistance to carbapenem, tigecycline, and polymyxin. Genomic analysis revealed that the IncHI1B/repB plasmid carried virulence factors (), while IncFII/IncR and IncFII plasmids harbored resistance genes [ ]. The coexistence of and in one hv-CRKP strain is exceptionally rare. Additionally, the Tet(A)-S251A variant in the conjugative plasmid pTET-4 may confer tigecycline resistance. Mutations in MgrB, PhoPQ, and PmrABCDK were identified as potential contributors to increased polymyxin resistance. Interestingly, plasmid-encoded restriction-modification systems and Retron regions were identified, which could potentially confer phage resistance.
The combination of virulence and antimicrobial resistance factors in the ST11-KL64 hv-CRKP strain represents a significant challenge for treating immunocompromised pediatric patients. Particularly concerning is the resistance to polymyxin and tigecycline, which are often last-resort treatments for multidrug-resistant infections. The findings highlight the urgent need for effective surveillance, infection control measures, and novel therapeutic strategies to manage such hypervirulent and multidrug-resistant pathogens.
高毒力碳青霉烯耐药肺炎克雷伯菌(hv-CRKP)因其治疗难度高和相关死亡率,对公共卫生构成了日益严重的风险,尤其是在骨髓移植(BMT)患者中。具有多种耐药机制的菌株的出现进一步使这些感染的管理复杂化。
我们从一名儿科骨髓移植患者中分离并鉴定了一株新型的ST11-KL64 hv-CRKP菌株。进行了药敏试验以确定耐药模式。进行了全面的基因组分析,以鉴定质粒类型、毒力因子和抗菌耐药基因,以及与突变和质粒介导变异相关的潜在耐药机制。
分离出的hv-CRKP菌株对碳青霉烯类、替加环素和多粘菌素表现出多重耐药性。基因组分析显示,IncHI1B/repB质粒携带毒力因子(),而IncFII/IncR和IncFII质粒含有耐药基因[ ]。在一株hv-CRKP菌株中同时存在 和 的情况极为罕见。此外,接合质粒pTET-4中的Tet(A)-S251A变异可能赋予替加环素耐药性。MgrB、PhoPQ和PmrABCDK中的突变被确定为多粘菌素耐药性增加的潜在因素。有趣的是,鉴定出了质粒编码的限制修饰系统和反转录子区域,它们可能赋予噬菌体抗性。
ST11-KL64 hv-CRKP菌株中毒力和抗菌耐药因子的组合对治疗免疫受损的儿科患者构成了重大挑战。特别令人担忧的是对多粘菌素和替加环素的耐药性,它们通常是治疗多重耐药感染的最后手段。这些发现凸显了有效监测、感染控制措施和新型治疗策略以管理此类高毒力和多重耐药病原体的迫切需求。