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.
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo, 143-8540, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshizumi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: David M
authors.initials: DM
authors.lastname: Livermore
authors.forename: Neil
authors.initials: N
authors.lastname: Woodford
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Saga
authors.forename: Sohei
authors.initials: S
authors.lastname: Harada
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load / Q000187:drug effects; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D015378:Imipenem / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; D004492:Edetic Acid; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1