Data_Sheet_1_Identification of a Novel Ceftazidime-Avibactam-Resistant KPC-2 Variant, KPC-123, in Citrobacter koseri Following Ceftazidime-Avibactam Treatment.PDF

This study reported the identification of a novel ceftazidime-avibactam-resistant KPC-2 variant, KPC-123, in a Citrobacter koseri isolated from a patient in a Chinese hospital following ceftazidime-avibactam treatment of infection caused by OXA-232-producing Klebsiella pneumoniae. This novel KPC-123 consisting of 302 amino acids differs from KPC-2 by two insertions after positions 179 (ins179_TY) and 270 (ins270_DDKHSEA), respectively. Conjugation and cloning experiments confirmed that KPC-123 was able to confer high-level resistance to ceftazidime and ceftazidime/avibactam (MICs of 128 mg/L and 64/4 mg/L, respectively) and elevated MIC values of cefotaxime, cefepime, and aztreonam (4 mg/L, 2 mg/L, and 4 mg/L, respectively) but retained susceptibility to carbapenems. Whole-genome sequencing and genomic analysis revealed that blaKPC−123 within the “ISKpn27-blaKPC-ISKpn6” structure was located on a 93,814-bp conjugative plasmid that was almost identical to a blaKPC−2-carrying plasmid harbored in a K. pneumoniae isolate from the same sampling site of the patient, suggesting the transfer and in vivo evolution of this blaKPC-carrying plasmid. Hence, active surveillance of ceftazidime/avibactam resistance and the underlying mechanisms, which may facilitate the prevention and control of the dissemination of resistance, is needed.

本研究报道了一株新型头孢他啶-阿维巴坦（ceftazidime-avibactam）耐药KPC-2变异株KPC-123，该变异株分离自中国某医院一名患者的科斯氏柠檬酸杆菌（Citrobacter koseri）样本；该患者此前因产OXA-232型β-内酰胺酶的肺炎克雷伯菌（Klebsiella pneumoniae）感染接受了头孢他啶-阿维巴坦治疗。该由302个氨基酸残基组成的新型KPC-123与KPC-2存在两处插入突变，分别位于第179位氨基酸后（ins179_TY）及第270位氨基酸后（ins270_DDKHSEA）。接合实验与克隆实验证实，KPC-123可赋予宿主菌对头孢他啶及头孢他啶/阿维巴坦的高水平耐药性（最低抑菌浓度（MIC）分别为128 mg/L及64/4 mg/L），同时可升高头孢噻肟、头孢吡肟及氨曲南的最低抑菌浓度（分别为4 mg/L、2 mg/L及4 mg/L），但仍对碳青霉烯类药物保持敏感性。全基因组测序与基因组分析显示，blaKPC-123位于「ISKpn27-blaKPC-ISKpn6」结构内，该结构整合于一条长度为93814 bp的接合性质粒上；该质粒与患者同一样本位点分离的一株携带blaKPC-2的肺炎克雷伯菌所携带的质粒几乎完全一致，提示此类携带blaKPC的质粒可发生水平转移并在宿主体内发生进化。因此，亟需开展针对头孢他啶/阿维巴坦耐药性及其潜在分子机制的主动监测，这将有助于防控耐药性的传播与扩散。