Resistance to ceftazidime-avibactam was reported, and it is important to investigate the mechanisms of ceftazidime/avibactam resistance in K. pneumoniae with mutations in blaKPC. We report the mutated blaKPC is not the only mechanism related to CZA resistance, and investigate the role of outer porin defects, efflux pump, and relative gene expression and copy number of blaKPC and ompk35/36. Four ceftazidime/avibactam-sensitive isolates detected wild type blaKPC-2, while 4 ceftazidime/avibactam-resistant isolates detected mutated blaKPC (blaKPC-51, blaKPC-52, and blaKPC-33). Compared with other ceftazidime/avibactam-resistant isolates with the minimal inhibitory concentration of ceftazidime/avibactam ranging 128–256 mg/L, the relative gene expression and copy number of blaKPC was increased in the isolate which carried blaKPC-51 and also showed the highest minimal inhibitory concentration of ceftazidime/avibactam at 2048 mg/L. The truncated Ompk35 contributes rare to ceftazidime/avibactam resistance in our isolates. No significant difference in minimal inhibitory concentration of ceftazidime/avibactam was observed after the addition of PABN. Increased gene expression and copy number of mutated blaKPC can cause high-level ceftazidime/avibactam resistance.

中文翻译：

---

突变的 blaKPC 基因表达和拷贝数增加导致肺炎克雷伯菌对头孢他啶/阿维巴坦产生高水平耐药

报道了对头孢他啶-阿维巴坦的耐药性，研究具有 blaKPC 突变的肺炎克雷伯菌对头孢他啶/阿维巴坦耐药的机制具有重要意义。我们报告突变的 blaKPC 不是与 CZA 抗性相关的唯一机制，并研究了外孔蛋白缺陷、外排泵以及 blaKPC 和 ompk35/36 的相对基因表达和拷贝数的作用。4 个对头孢他啶/avibactam 敏感的分离株检测到野生型 blaKPC-2，而 4 个对头孢他啶/avibactam 耐药的分离株检测到突变的 blaKPC（blaKPC-51、blaKPC-52 和 blaKPC-33）。与其他头孢他啶/阿维巴坦耐药菌株相比，头孢他啶/阿维巴坦的最低抑菌浓度范围为128-256 mg/L，携带blaKPC-51的分离株中blaKPC的相对基因表达和拷贝数增加，头孢他啶/阿维巴坦的最低抑菌浓度最高为2048 mg/L。截短的 Ompk35 在我们的分离物中很少导致头孢他啶/阿维巴坦耐药性。添加 PABN 后，头孢他啶/阿维巴坦的最小抑制浓度没有显着差异。突变 blaKPC 的基因表达和拷贝数增加可导致高水平的头孢他啶/阿维巴坦耐药性。