Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 beta-lactamase.
Project/Area Number |
25461523
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Infectious disease medicine
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Research Institution | Gunma Paz University (2016) Toho University (2013-2015) |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | NDM-1 / ニューデリーメタロベータラクタマーゼ / Ca-EDTA |
Outline of Final Research Achievements |
We evaluated the efficacy of Ca-EDTA, as an inhibitor for New Delhi Metallo-β-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 512mg/L, imipenem/Ca-EDTA 2mg/L.) 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 2.3x103 CFU/liver, compared with 2.9×104 CFU/liver for IPM/CS alone. These data demonstrated the possibility of Ca-EDTA for clinical applications. Also, IL-6 serum levels in septic animals were reduced after the combination therapy using imipenem/cilastatin sodium (IPM/CS) and Ca-EDTA, although further study is needed. 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.
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Report
(5 results)
Research Products
(4 results)
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[Journal Article] IMP-27, a Unique Metallo-beta-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis.2016
Author(s)
Dixon N, Fowler RC, Yoshizumi A, Horiyama T, Ishii Y, Harrison L, Geyer CN, Moland ES, Thomson K, Hanson ND.
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Journal Title
Antimicrob Agents Chemother.
Volume: 60
Issue: 10
Pages: 6418-6421
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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