PDF(Pubmed)
Abstract：
UNASSIGNED: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective β-lactam/β-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by Klebsiella pneumoniae carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant K. pneumoniae.
UNASSIGNED: The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.
UNASSIGNED: Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of bla KPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.
UNASSIGNED: Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying bla KPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.
UNASSIGNED: The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.
UNASSIGNED: Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of bla KPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.
UNASSIGNED: Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying bla KPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.
摘要：
■耐碳青霉烯类肺炎克雷伯菌（CRKP）感染是全球公共卫生的巨大威胁。头孢他啶-阿维巴坦（CZA）是一种有效的抗CRKP的β-内酰胺/β-内酰胺酶抑制剂。然而,对CZA的抗性报告，主要由肺炎克雷伯菌碳青霉烯酶（KPC）变异体引起，近年来有所增加。在这项研究中,我们的目的是描述KPC-12的耐药特征,这是一种从CZA耐药肺炎克雷伯菌中鉴定出的新型KPC变异体.
■从呼吸道感染患者收集的肺炎克雷伯菌YFKP-97在IlluminaNovaSeq6000平台上进行了全基因组测序（WGS）。使用生物信息学方法分析基因组特征。通过肉汤微量稀释法进行抗菌药敏感性测试。如前所述在体外进行抗性菌株的诱导。采用G.mellonella杀灭试验评价菌株的致病性，并进行接合实验以评估质粒转移能力。
■菌株YFKP-97是一种多重耐药的临床ST11-KL47肺炎克雷伯菌，对CZA（16/4μg/mL）具有高度耐药性。WGS透露，KPC变体，KPC-12由IncFII（pHN7A8）质粒（pYFKP-97_a和pYFKP-97_b）携带，对碳青霉烯类抗生素的活性显着降低。此外,blaKPC-12对其对头孢他啶的活性具有剂量依赖性作用.体外诱导型抗性测定结果表明,KPC-12变体比KPC-2和KPC-3变体更可能赋予对CZA的抗性。
■我们的研究表明，未接受CZA治疗的患者也可能感染具有新型KPC变体的CZA抗性菌株。鉴于携带blaKPC-12的转化体更可能表现出CZA抗性表型。因此,尽早准确识别KPC变异非常重要.
■从呼吸道感染患者收集的肺炎克雷伯菌YFKP-97在IlluminaNovaSeq6000平台上进行了全基因组测序（WGS）。使用生物信息学方法分析基因组特征。通过肉汤微量稀释法进行抗菌药敏感性测试。如前所述在体外进行抗性菌株的诱导。采用G.mellonella杀灭试验评价菌株的致病性，并进行接合实验以评估质粒转移能力。
■菌株YFKP-97是一种多重耐药的临床ST11-KL47肺炎克雷伯菌，对CZA（16/4μg/mL）具有高度耐药性。WGS透露，KPC变体，KPC-12由IncFII（pHN7A8）质粒（pYFKP-97_a和pYFKP-97_b）携带，对碳青霉烯类抗生素的活性显着降低。此外,blaKPC-12对其对头孢他啶的活性具有剂量依赖性作用.体外诱导型抗性测定结果表明,KPC-12变体比KPC-2和KPC-3变体更可能赋予对CZA的抗性。
■我们的研究表明，未接受CZA治疗的患者也可能感染具有新型KPC变体的CZA抗性菌株。鉴于携带blaKPC-12的转化体更可能表现出CZA抗性表型。因此,尽早准确识别KPC变异非常重要.
