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In vitro activity of sitafloxacin against Mycobacterium tuberculosis with gyrA/B mutations isolated in Japan

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タイトル: In vitro activity of sitafloxacin against Mycobacterium tuberculosis with gyrA/B mutations isolated in Japan
その他のタイトル: 日本で分離されたgyrA/B 変異結核菌株のin vitroでのシタフロキサシン活性の評価
著者: 伊, 麗娜
著者(別表記) : Yi, Lina
発行日: 2017年 9月20日
出版者: Microbiology Society
引用: Nagasaki University (長崎大学), 博士(医学) (2017-09-20)
抄録: Purpose. Sitafloxacin (SFX) is a new fluoroquinolone (FQ) that has shown a strong bactericidal effect against Mycobacterium tuberculosis (Mtb) in vitro. However, data on SFX efficacy against Mtb with gyrA/B mutations and its epidemiological cut-off (ECOFF) value remain limited. Therefore, we evaluated and compared the in vitro activity of SFX against gyrA/B-mutant Mtb to that of moxifloxacin (MFX), levofloxacin (LFX) and ciprofloxacin (CFX), and determined the ECOFF for SFX. Methodology. A total of 109 clinical Mtb isolates, including 73 multidrug-resistant (MDR) isolates, were subjected to minimum inhibitory concentration (MIC) analysis in oleic-albumin-dextrose-catalase (OADC)-supplemented Middlebrook 7H9 medium. Our results showed that SFX had lower cumulative MIC than MFX, LFX and CFX. Furthermore, we performed direct DNA sequencing of the quinolone-resistance-determining regions (QRDRs). Results. We identified the following mutations: D94G, D94A, A90V, D94H, D94N and G88A in gyrA; and A543V, A543T, E540D, R485C, D500A, I552S and D577A in gyrB. Based on our results, an ECOFF of 0.125 µg ml−1 was proposed for SFX. With this ECOFF, 15 % of LFX-resistant isolates with MIC ≥2 µg ml−1 were susceptible to SFX. Conclusion. SFX had the lowest cumulative MIC and a relatively low ECOFF value against Mtb, indicating that SFX was not only more effective against gyrA-mutant isolates, but also MDR isolates in Japan.
記述: 長崎大学学位論文 学位記番号:博(医歯薬)甲第1000号 学位授与年月日:平成29年9月20日 / Author: Lina Yi​​, Akio Aono​, Kinuyo Chikamatsu​, Yuriko Igarashi​, Hiroyuki Yamada​, Akiko Takaki​, Satoshi Mitarai​ / Citation: Journal of Medical Microbiology, 66(6), pp.770-776; 2017
キーワード: epidemiological cut-off value / minimum inhibitory concentrations / gyrase A gene / sitafloxacin / gyrase B gene
URI: http://hdl.handle.net/10069/37902
ISSN: 00222615
DOI: 10.1099/jmm.0.000493
関連リンク : http://hdl.handle.net/10069/37811
権利: © 2017 The Authors. Published by the Microbiology Society.
資料タイプ: Thesis or Dissertation
原稿種類: ETD
出現コレクション:110 学位論文

引用URI : http://hdl.handle.net/10069/37902



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