Activities of aztreonam in combination with several novel β-lactam-β-lactamase inhibitor combinations against carbapenem-resistant <i>Klebsiella pneumoniae</i> strains coproducing KPC and NDM

作者全名："Li, Xinhui; Zhang, Jisheng; Wang, Jianmin; Long, Wenzhang; Liang, Xushan; Yang, Yang; Gong, Xue; Li, Jie; Liu, Longjin; Zhang, Xiaoli"

作者地址："[Li, Xinhui; Zhang, Jisheng; Wang, Jianmin; Long, Wenzhang; Liang, Xushan; Yang, Yang; Gong, Xue; Li, Jie; Liu, Longjin; Zhang, Xiaoli] Chongqing Med Univ, Dept Microbiol, Yongchuan Hosp, Chongqing, Peoples R China"

通信作者："Zhang, XL (通讯作者)，Chongqing Med Univ, Dept Microbiol, Yongchuan Hosp, Chongqing, Peoples R China."

来源：FRONTIERS IN MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001187183800001

JCR分区：Q2

影响因子：4

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：carbapenem-resistant Klebsiella pneumoniae; beta-lactamase inhibitor; bactericidal effect; time-kill assay; aztreonam

摘要："Isolates coproducing serine/metallo-carbapenems are a serious emerging public health threat, given their rapid dissemination and the limited number of treatment options. The purposes of this study were to evaluate the in vitro antibacterial activity of novel beta-lactam-beta-lactamase inhibitor combinations (BLBLIs) against carbapenem-resistant Klebsiella pneumoniae (CRKP) coproducing metallo-beta-lactamase and serine-beta-lactamase, and to explore their effects in combination with aztreonam, meropenem, or polymyxin in order to identify the best therapeutic options. Four CRKP isolates coproducing K. pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM) were selected, and a microdilution broth method was used to determine their susceptibility to antibiotics. Time-kill assay was used to detect the bactericidal effects of the combinations of antibiotics. The minimum inhibitory concentration (MIC) values for imipenem and meropenem in three isolates did not decrease after the addition of relebactam or varbobactam, but the addition of avibactam to aztreonam reduced the MIC by more than 64-fold. Time-kill assay demonstrated that imipenem-cilastatin/relebactam (ICR) alone exerted a bacteriostatic effect against three isolates (average reduction: 1.88 log(10) CFU/mL) and ICR combined with aztreonam exerted an additive effect. Aztreonam combined with meropenem/varbobactam (MEV) or ceftazidime/avibactam (CZA) showed synergistic effects, while the effect of aztreonam combined with CZA was inferior to that of MEV. Compared with the same concentration of aztreonam plus CZA combination, aztreonam/avibactam had a better bactericidal effect (24 h bacterial count reduction >3 log10CFU/mL). These data indicate that the combination of ATM with several new BLBLIs exerts powerful bactericidal activity, which suggests that these double beta-lactam combinations might provide potential alternative treatments for infections caused by pathogens coproducing-serine/metallo-carbapenems."

基金机构："General Projects of Chongqing Natural Science Foundation [cstc2020jcyj-msxm0067]; Yongchuan Natural Science Foundation [2021yc-jckx20053]; Talent Introduction project of Yongchuan Hospital of Chongqing Medical University [YJYJ202004, YJYJ202005]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0113]"

基金资助正文："This work was supported by the General Projects of Chongqing Natural Science Foundation (cstc2020jcyj-msxm0067); Yongchuan Natural Science Foundation (2021yc-jckx20053); the Talent Introduction project of Yongchuan Hospital of Chongqing Medical University (YJYJ202004 and YJYJ202005); and the Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0113)."