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

Ayumi Yoshizumi; Yoshikazu Ishii; David M Livermore; Neil Woodford; Soichiro Kimura; Tomoo Saga; Sohei Harada; Keizo Yamaguchi; Kazuhiro Tateda

doi:10.1007/s10156-012-0528-y

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

Ayumi Yoshizumi, Yoshikazu Ishii, David M Livermore, Neil Woodford, Soichiro Kimura, Tomoo Saga, Sohei Harada, Keizo Yamaguchi, Kazuhiro Tateda

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Abstract

We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (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 (IPM) ≤1-2 μg/ml; meropenem (MEPM) ≤1-4 µg/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 × 10(3) CFU/liver, compared with 2.9 × 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.

Original language	English
Pages (from-to)	992-5
Number of pages	4
Journal	Journal of Infection and Chemotherapy
Volume	19
Issue number	5
DOIs	https://doi.org/10.1007/s10156-012-0528-y
Publication status	Published - Oct 2013

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10.1007/s10156-012-0528-y

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@article{2c3b53a9782d4e7b912515304bd67019,

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

abstract = "We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (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 (IPM) ≤1-2 μg/ml; meropenem (MEPM) ≤1-4 µg/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 × 10(3) CFU/liver, compared with 2.9 × 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.",

author = "Ayumi Yoshizumi and Yoshikazu Ishii and Livermore, {David M} and Neil Woodford and Soichiro Kimura and Tomoo Saga and Sohei Harada and Keizo Yamaguchi and Kazuhiro Tateda",

year = "2013",

month = oct,

doi = "10.1007/s10156-012-0528-y",

language = "English",

volume = "19",

pages = "992--5",

journal = "Journal of Infection and Chemotherapy",

issn = "1341-321X",

publisher = "Elsevier",

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TY - JOUR

T1 - Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase

AU - Yoshizumi, Ayumi

AU - Ishii, Yoshikazu

AU - Livermore, David M

AU - Woodford, Neil

AU - Kimura, Soichiro

AU - Saga, Tomoo

AU - Harada, Sohei

AU - Yamaguchi, Keizo

AU - Tateda, Kazuhiro

PY - 2013/10

Y1 - 2013/10

N2 - We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (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 (IPM) ≤1-2 μg/ml; meropenem (MEPM) ≤1-4 µg/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 × 10(3) CFU/liver, compared with 2.9 × 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.

AB - We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (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 (IPM) ≤1-2 μg/ml; meropenem (MEPM) ≤1-4 µg/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 × 10(3) CFU/liver, compared with 2.9 × 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.

U2 - 10.1007/s10156-012-0528-y

DO - 10.1007/s10156-012-0528-y

M3 - Article

C2 - 23233082

VL - 19

SP - 992

EP - 995

JO - Journal of Infection and Chemotherapy

JF - Journal of Infection and Chemotherapy

SN - 1341-321X

IS - 5

ER -