单位：[1]National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, China.[2]Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.[3]National Clinical Research Center of Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.[4]Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, China.[5]Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.
Background Resistance to ceftazidime-avibactam was reported, and it is important to investigate the mechanisms of ceftazidime/avibactam resistance in K. pneumoniae with mutations in bla(KPC). Results We report the mutated bla(KPC) 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 bla(KPC) and ompk35/36. Four ceftazidime/avibactam-sensitive isolates detected wild type bla(KPC-2), while 4 ceftazidime/avibactam-resistant isolates detected mutated bla(KPC) (bla(KPC-51), bla(KPC-52), and bla(KPC-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 bla(KPC) was increased in the isolate which carried bla(KPC-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. Conclusions Increased gene expression and copy number of mutated bla(KPC) can cause high-level ceftazidime/avibactam resistance.
基金：
National Key R&D Program of China [2017YFC1309301, 2017YFC1309300]; CAMS Innovation Fund for Medical Sciences [CIFMS 2018-I2M-1-003]; National Science Grant for Distinguished Young Scholars [81425001/H0104]
第一作者单位：[1]National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, China.[2]Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.[3]National Clinical Research Center of Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.
通讯作者：
通讯机构：[1]National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, China.[2]Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.[3]National Clinical Research Center of Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.[5]Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.
推荐引用方式(GB/T 7714)：
Lingxiao Sun,Haibo Li,Qi Wang,et al.Increased gene expression and copy number of mutated bla(KPC) lead to high-level ceftazidime/avibactam resistance in Klebsiella pneumoniae[J].BMC MICROBIOLOGY.2021,21(1):doi:10.1186/s12866-021-02293-0.
APA：
Lingxiao Sun,Haibo Li,Qi Wang,Yingmei Liu&Bin Cao.(2021).Increased gene expression and copy number of mutated bla(KPC) lead to high-level ceftazidime/avibactam resistance in Klebsiella pneumoniae.BMC MICROBIOLOGY,21,(1)
MLA：
Lingxiao Sun,et al."Increased gene expression and copy number of mutated bla(KPC) lead to high-level ceftazidime/avibactam resistance in Klebsiella pneumoniae".BMC MICROBIOLOGY 21..1(2021)
