Wu Wenhao, Ni Shuangling, Zheng Yi, Zhang Piaopiao, Jiang Yan, Li Xi, Yu Yunsong, Qu Tingting
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Infectious Disease, Lishui City People's Hospital, Lishui, Zhejiang Province, China.
Int J Antimicrob Agents. 2024 Dec;64(6):107373. doi: 10.1016/j.ijantimicag.2024.107373. Epub 2024 Oct 30.
Hypervirulent Klebsiella pneumoniae (hvKp) poses a serious public health threat. Gas gangrene caused by hvKp is rarely reported and potentially results in a poor prognosis. This study describes the case of a hospitalised patient with gas gangrene and sepsis caused by hvKP. Carbapenem-susceptible hypervirulent Klebsiella pneumoniae (CS-hvKp) strains KPLSN and KPLSX were isolated from the knee joint pus and blood specimens of the patient for further investigations. Whole genome sequencing revealed that KPLSN and KPLSX were highly homologous (single nucleotide polymorphisms [SNPs]<10) and belonged to ST412/K57. The minimum inhibitory concentration and minimum bactericidal concentration under biofilm values of meropenem in KPLSN and KPLSX were significantly higher than in the planktonic state (>128 mg/L vs. 0.25 mg/L, P<0.0001). These two strains had high biofilm formation ability, and the results from fluorescence staining experiments showed that they were not easily killed by meropenem in the biofilm state. KPLSN and KPLSX showed high capsule production and were confirmed to have high virulence through experiments with the Galleria mellonella infection model and the BALB/c mice abdominal infection model. The persistent symptoms may be due to enhanced biofilm and capsule formation. Phylogenetic analysis of global ST412 strains showed their evolution towards higher virulence and resistance. These results emphasise the critical need for judicious antibiotic use and novel therapeutic approaches to combat special infections caused by these pathogens.
高毒力肺炎克雷伯菌(hvKp)对公众健康构成严重威胁。由hvKp引起的气性坏疽鲜有报道,且可能导致预后不良。本研究描述了一名因hvKP导致气性坏疽和败血症的住院患者病例。从该患者的膝关节脓液和血液标本中分离出对碳青霉烯敏感的高毒力肺炎克雷伯菌(CS-hvKp)菌株KPLSN和KPLSX,用于进一步研究。全基因组测序显示,KPLSN和KPLSX高度同源(单核苷酸多态性[SNPs]<10),属于ST412/K57。KPLSN和KPLSX中,美罗培南在生物膜状态下的最低抑菌浓度和最低杀菌浓度显著高于浮游状态(>128 mg/L对0.25 mg/L,P<0.0001)。这两株菌具有较高的生物膜形成能力,荧光染色实验结果表明,它们在生物膜状态下不易被美罗培南杀死。KPLSN和KPLSX显示出高荚膜产量,并通过用大蜡螟感染模型和BALB/c小鼠腹部感染模型进行的实验证实具有高毒力。持续症状可能归因于生物膜和荚膜形成增强。对全球ST412菌株的系统发育分析表明它们正向更高毒力和耐药性进化。这些结果强调了明智使用抗生素和采用新型治疗方法来对抗由这些病原体引起的特殊感染的迫切需求。