| Title | Increased gene expression and copy number of mutated bla(KPC) lead to high-level ceftazidime/avibactam resistance in Klebsiella pneumoniae |
| Authors | Sun, Lingxiao Li, Haibo Wang, Qi Liu, Yingmei Cao, Bin |
| Affiliation | Capital Med Univ, China Japan Friendship Hosp, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China China Japan Friendship Hosp, Ctr Resp Dis, Dept Pulm & Crit Care Med, Lab Clin Cal Microbiol & Infect Dis, Beijing, Peoples R China Chinese Acad Med Sci, Inst Resp Med, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China Peking Univ Peoples Hosp, Dept Clin Lab, Beijing, Peoples R China Tsinghua Univ Peking Univ Joint Ctr Life Sci, Beijing, Peoples R China |
| Keywords | AVIBACTAM RESISTANCE SUSCEPTIBILITY |
| Issue Date | 19-Aug-2021 |
| Publisher | BMC MICROBIOLOGY |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/623772 |
| ISSN | 1471-2180 |
| DOI | 10.1186/s12866-021-02293-0 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 生命科学学院 |
