國家衛生研究院 NHRI:Item 3990099045/15839
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    题名: The individual contributions of blaB, blaGOB and blaCME on MICs of Beta-lactams in Elizabethkingia anophelis
    其它题名: The individual contributions of blaB, blaGOB and blaCME on MICs of β-lactams in Elizabethkingia anophelis
    作者: Chen, PJ;Tan, MC;Huang, WC;Hsu, SY;Chen, TL;Yang, CY;Kuo, SC
    贡献者: National Institute of Infectious Diseases and Vaccinology;Institute of Population Health Sciences
    摘要: Background: The bla(B), bla(GOB) and bla(CME) genes are thought to confer beta-lactam resistance to Elizabethkingia anophelis, based on experiments conducted primarily on Escherichia coli. Objectives: To determine the individual contributions of beta-lactamase genes to increased MICs in E. anophelis and to assess their impact on the in vivo efficacy of carbapenem therapy. Methods: Scarless gene deletion of one or more beta-lactamase gene(s) was performed in three clinical E. anophelis isolates. MICs were determined by broth microdilution. Hydrolytic activity and expressions of beta-lactamase genes were measured by an enzymatic assay and quantitative RT-PCR, respectively. In vivo efficacy was determined using Galleria mellonella and murine thigh infection models. Results: The presence of bla(B) resulted in >16-fold increases, while bla(GOB) caused 4-16-fold increases of carbapenem MICs. Hydrolysis of carbapenems was highest in lysates of bla(B)-positive strains, possibly due to the constitutionally higher expression of bla(B). Imipenem was ineffective against blaB-positive isolates in vivo in terms of improvement of the survival of wax moth larvae and reduction of murine bacterial load. The deletion of bla(B) restored the efficacy of imipenem. The bla(B) gene was also responsible for a >4-fold increase of ampicillin/sulbactam and piperacillin/tazobactam MICs. The presence of bla(CME), but not bla(B) or bla(GOB), increased the MICs of ceftazidime and cefepime by 8-16- and 4-8-fold, respectively. Conclusions: The constitutionally and highly expressed bla(B) gene in E. anophelis was responsible for increased MICs of carbapenems and led to their poor in vivo efficacy. bla(CME) increased the MICs of ceftazidime and cefepime.
    日期: 2024-07
    關聯: Journal of Antimicrobial Chemotherapy. 2024 Jul;79(7):1577-1580.
    Link to: http://dx.doi.org/10.1093/jac/dkae137
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0305-7453&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001222049700001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85197633081
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