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.

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 o...

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Autores principales:	Fangzhou Wang, Qian Zhou, Xiuwen Yang, Yan Bai, Junchang Cui
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4327301612124de19a433cbaa743c552
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spelling	oai:doaj.org-article:4327301612124de19a433cbaa743c5522021-12-02T20:19:13ZEvaluation 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.1932-620310.1371/journal.pone.0258426https://doaj.org/article/4327301612124de19a433cbaa743c5522021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258426https://doaj.org/toc/1932-6203Klebsiella 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.Fangzhou WangQian ZhouXiuwen YangYan BaiJunchang CuiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258426 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fangzhou Wang Qian Zhou Xiuwen Yang Yan Bai Junchang Cui 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.
description	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.
format	article
author	Fangzhou Wang Qian Zhou Xiuwen Yang Yan Bai Junchang Cui
author_facet	Fangzhou Wang Qian Zhou Xiuwen Yang Yan Bai Junchang Cui
author_sort	Fangzhou Wang
title	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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4327301612124de19a433cbaa743c552
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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.

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