Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase

被引:51
|
作者
Yoshizumi, Ayumi [1 ]
Ishii, Yoshikazu [1 ]
Livermore, David M. [2 ,3 ]
Woodford, Neil [2 ]
Kimura, Soichiro [1 ]
Saga, Tomoo [1 ]
Harada, Sohei [1 ]
Yamaguchi, Keizo [1 ]
Tateda, Kazuhiro [1 ]
机构
[1] Toho Univ, Sch Med, Fac Med, Dept Microbiol & Infect Dis, Tokyo 1438540, Japan
[2] Hlth Protect Agcy, Antibiot Resistance Monitoring & Reference Lab, London, England
[3] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England
关键词
Antibiotic resistance; NDM-1; Metallo-beta-lactamase inhibitor; Calcium-EDTA; ACINETOBACTER-BAUMANNII; CHELATION-THERAPY; RESISTANCE; EMERGENCE;
D O I
10.1007/s10156-012-0528-y
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (Ca-EDTA), as an inhibitor for New Delhi metallo-beta-lactamase-1 (NDM-1) in vitro antibiotic susceptibility and in a mouse model of sepsis caused by Escherichia coli. Ca-EDTA drastically reduced the MICs of carbapenems for all NDM-producing bacteria [imipenem (IPM) a parts per thousand currency sign1-2 mu g/ml; meropenem (MEPM) a parts per thousand currency sign1-4 A mu g/ml]. In the neutropenic murine model of sepsis, the bacterial burden was further reduced by combination therapy using imipenem/cilastatin sodium (IPM/CS) and Ca-EDTA to 2.3 x 10(3) CFU/liver, compared with 2.9 x 10(4) CFU/liver for IPM/CS alone. These data demonstrated the possibility of Ca-EDTA for clinical applications. In our understanding, this is the first report examining the effect of Ca-EDTA on a mouse sepsis model caused by NDM-1-producing bacteria.
引用
收藏
页码:992 / 995
页数:4
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