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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

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 × 10³ CFU/liver, compared with 2.9 × 10⁴ 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)	992-995
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

Bibliographical note

Funding Information:
Acknowledgments This study was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 22591113 to Y.I.).

Keywords

Antibiotic resistance
Calcium-EDTA
Metallo-β-lactamase inhibitor
NDM-1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10156-012-0528-y

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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 × 103 CFU/liver, compared with 2.9 × 104 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.",

keywords = "Antibiotic resistance, Calcium-EDTA, Metallo-β-lactamase inhibitor, NDM-1",

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",

note = "Funding Information: Acknowledgments This study was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 22591113 to Y.I.).",

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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

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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 × 103 CFU/liver, compared with 2.9 × 104 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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