肺炎克雷伯菌
多粘菌素B
抗生素
多粘菌素
微生物学
基因型
生物
医学
大肠杆菌
遗传学
基因
作者
Yuan Wang,Tao Chen,Xiaohui Chi,Yanzi Zhou,Hao Fu,Ping Lü,Luying Xiong,Tingting Xiao,Beiwen Zheng,Ping Shen,Qixia Luo,Yonghong Xiao
标识
DOI:10.1016/j.cmi.2023.06.029
摘要
ObjectivesThe emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major clinical concern, and polymyxin B (PMB) is a ‘last resort’ antibiotic for its treatment. Understanding the effects of drug susceptibility transformation in CRKP-infected patients undergoing PMB treatment would be beneficial to optimize PMB treatment strategies.MethodsWe retrospectively collected data from patients infected with CRKP and treated with PMB from January 2018 to December 2020. CRKPs were collected before and after PMB therapy, and patients were classified as ‘transformation’ group (TG) and ‘non-transformation’ group (NTG) by the shift of susceptibility to PMB. We compared clinical characteristics between these groups, and further analyzed the phenotypic and genome variation of the CRKP after PMB susceptibility transformation.ResultsA total of 160 patients (37 in the TG, 123 in the NTG) were included in this study. The duration of PMB treatment before PMB-resistant K. pneumoniae (PRKP) appearance in TG were even longer than the whole duration of PMB treatment in NTG (8 (8) days vs. 7 (6) days; P=0.0496). When compared with isogenic PMB-susceptible K. pneumoniae (PSKP), most PRKP strains had missense mutations in mgrB (12 isolates), yciC (10 isolates), and pmrB (seven isolates). The competition index of 82.4% (28/34) of PRKP/PSKP pairs was less than 1. 67.6% (23/34) and 73.5% (25/34) of PRKP strains showed a higher 7 day lethality in Galleria mellonella and a greater ability to resist complement-dependent killing than their corresponding PSKP, respectively.ConclusionsLow-dose with longer PMB treatment durations may associated with emergence of polymyxin resistance. The evolution of PRKP is predominantly mediated by an accumulation of mutations, including those in mgrB, yciC, and pmrB. Lastly, PRKP exhibited reduced growth and increased virulence compared with parental PSKP.
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