論文

査読有り 国際誌
2019年4月

Analysis of synergy between beta-lactams and anti-methicillin-resistant Staphylococcus aureus agents from the standpoint of strain characteristics and binding action.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
  • Daisuke Ono
  • Tetsuo Yamaguchi
  • Masakaze Hamada
  • Shiro Sonoda
  • Ayami Sato
  • Kotaro Aoki
  • Chiaki Kajiwara
  • Soichiro Kimura
  • Momoko Fujisaki
  • Hiroyuki Tojo
  • Masakazu Sasaki
  • Hinako Murakami
  • Keisuke Kato
  • Yoshikazu Ishii
  • Kazuhiro Tateda
  • 全て表示

25
4
開始ページ
273
終了ページ
280
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jiac.2018.12.007

In light of the increasing number of clinical cases resistant to traditional monotherapies and the lack of novel antimicrobial agents, combination therapy is an appealing solution for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we evaluated the efficacy of anti-MRSA agents, such as vancomycin (VAN), daptomycin (DAP), and linezolid (LZD), in conjunction with 13 beta-lactams and non-beta-lactams. We assessed the in vitro activities of the various combinations against 40 MRSA strains based on the maximum synergistic effect (MSE), an index calculated from the MIC change with a combination agent. Nearly all the anti-MRSA agents, which were combined with beta-lactams as well as VAN and DAP, showed a synergistic effect with arbekacin. VAN also exhibited varying degrees of synergy depending on the type of beta-lactam, whereas DAP and LZD showed similar synergy with different beta-lactams. These effects were confirmed by antibiotic kill curves, except for the apparent interaction between LZD and beta-lactams. The MSE results were analyzed according to strain characteristics including susceptibility to combination agents, staphylococcal cassette chromosome mec type, and presence of the blaZ gene; however, no obvious correlations were observed. In a fluorescence binding assay, the fluorescence intensity of boron-dipyrromethene (BODIPY)-VAN decreased, whereas that of BODIPY-DAP increased in combination with a beta-lactam agent. These findings suggest that beta-lactam combinations are promising treatment options for MRSA infections and that the type of beta-lactam combined with VAN is important for the synergistic effect.

リンク情報
DOI
https://doi.org/10.1016/j.jiac.2018.12.007
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30713034
ID情報
  • DOI : 10.1016/j.jiac.2018.12.007
  • PubMed ID : 30713034

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