| 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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| 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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