Evaluation of ceftazidime/avibactam alone and in combination with amikacin, colistin and tigecycline against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae by in vitro time-kill experiment
机构：[1]Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.[2]Department of Respiratory Diseases, People's Hospital of Hainan District, Wuhai, China.[3]Center for Life Sciences, School of Life Sciences, Yunnan University, Chenggong District, Kunming, China.
Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) poses a major threat to human health worldwide. Combination therapies of antibiotics with different mechanisms have been recommended in literatures. This study assessed in vitro antibacterial activities and synergistic activities of ceftazidime/avibactam alone and in combinations against KPC-Kp. In total, 70 isolates from 2 hospitals in Beijing were examined in our study. By using the agar dilution method and broth dilution method, we determined the minimum inhibitory concentration (MIC) of candidate antibiotics. Ceftazidime/avibactam demonstrated promising susceptibility against KPC-Kp (97.14%). Synergistic activities testing was achieved by checkerboard method and found ceftazidime/avibactam-amikacin displayed synergism in 90% isolates. Ceftazidime/avibactam-colistin displayed partial synergistic in 43% isolates, and ceftazidime/avibactam-tigecycline displayed indifference in 67% isolates. In time-kill assays, antibiotics at 1-fold MIC were mixed with bacteria at 1 × 105 CFU/ml and Mueller-Hinton broth (MHB). Combinations of ceftazidime/avibactam with amikacin and tigecycline displayed better antibacterial effects than single drug. Ceftazidime/avibactam-colistin combination did not exhibit better effect than single drug. In KPC-Kp infections, susceptibility testing suggested that ceftazidime/avibactam may be considered as first-line choice. However, monotherapy is often inadequate in infection management. Thus, our study revealed that combination therapy including ceftazidime/avibactam colistin and ceftazidime/avibactam tigecycline may benefit than monotherapy in KPC-Kp treatment. Further pharmacokinetic/pharmacodynamic and mutant prevention concentration studies should be performed to optimize multidrug-regimens.
基金：
This work was supported by the Military
Biosafety Research Fund (No. 19SWAQ06).
Junchang Cui received this fund and the funders
had no role in study design, data collection and
analysis, decision to publish, or preparation of the
manuscript.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
最新[2023]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Fangzhou,Zhou Qian,Yang Xiuwen,et al.Evaluation of ceftazidime/avibactam alone and in combination with amikacin, colistin and tigecycline against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae by in vitro time-kill experiment[J].PloS one.2021,16(10):e0258426.doi:10.1371/journal.pone.0258426.
APA：
Wang Fangzhou,Zhou Qian,Yang Xiuwen,Bai Yan&Cui Junchang.(2021).Evaluation of ceftazidime/avibactam alone and in combination with amikacin, colistin and tigecycline against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae by in vitro time-kill experiment.PloS one,16,(10)
MLA：
Wang Fangzhou,et al."Evaluation of ceftazidime/avibactam alone and in combination with amikacin, colistin and tigecycline against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae by in vitro time-kill experiment".PloS one 16..10(2021):e0258426
