In vivo targeting of escherichia coli with vancomycin-arginine

Lewis F. Neville; Itamar Shalit; Peter A. Warn; Marc H. Scheetz; Jiuzhi Sun; Madeline B. Chosy; Paul A. Wender; Lynette Cegelski; Jacob T. Rendell

doi:10.1128/AAC.02416-20

In vivo targeting of escherichia coli with vancomycin-arginine

Lewis F. Neville^*, Itamar Shalit, Peter A. Warn, Marc H. Scheetz, Jiuzhi Sun, Madeline B. Chosy, Paul A. Wender, Lynette Cegelski, Jacob T. Rendell

^*Corresponding author for this work

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

19 Scopus citations

Abstract

The ability of vancomycin-arginine (V-r) to extend the spectrum of activity of glycopeptides to Gram-negative bacteria was investigated. Its MIC towards Escherichia coli, including b-lactamase expressing Ambler classes A, B, and D, was 8 to 16 mg/ml. Addition of 8 times the MIC of V-r to E. coli was acutely bactericidal and associated with a low frequency of resistance (,2.32 × 102¹⁰). In vivo, V-r markedly reduced E. coli burden by .7 log₁₀ CFU/g in a thigh muscle model. These data warrant further development of V-r in combatting E. coli, including resistant forms.

Original language	English
Article number	e02416-20
Journal	Antimicrobial Agents and Chemotherapy
Volume	65
Issue number	4
DOIs	https://doi.org/10.1128/AAC.02416-20
State	Published - Apr 2021
Externally published	Yes

Keywords

Antibiotic resistance
Arginine
Cationic peptides
Escherichia coli
Gram-negative bacteria
Multidrug resistance
Vancomycin conjugate

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10.1128/AAC.02416-20

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title = "In vivo targeting of escherichia coli with vancomycin-arginine",

abstract = "The ability of vancomycin-arginine (V-r) to extend the spectrum of activity of glycopeptides to Gram-negative bacteria was investigated. Its MIC towards Escherichia coli, including b-lactamase expressing Ambler classes A, B, and D, was 8 to 16 mg/ml. Addition of 8 times the MIC of V-r to E. coli was acutely bactericidal and associated with a low frequency of resistance (,2.32 × 10210). In vivo, V-r markedly reduced E. coli burden by .7 log10 CFU/g in a thigh muscle model. These data warrant further development of V-r in combatting E. coli, including resistant forms.",

keywords = "Antibiotic resistance, Arginine, Cationic peptides, Escherichia coli, Gram-negative bacteria, Multidrug resistance, Vancomycin conjugate",

author = "Neville, {Lewis F.} and Itamar Shalit and Warn, {Peter A.} and Scheetz, {Marc H.} and Jiuzhi Sun and Chosy, {Madeline B.} and Wender, {Paul A.} and Lynette Cegelski and Rendell, {Jacob T.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Neville et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.",

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doi = "10.1128/AAC.02416-20",

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AU - Neville, Lewis F.

AU - Shalit, Itamar

AU - Warn, Peter A.

AU - Scheetz, Marc H.

AU - Sun, Jiuzhi

AU - Chosy, Madeline B.

AU - Wender, Paul A.

AU - Cegelski, Lynette

AU - Rendell, Jacob T.

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AB - The ability of vancomycin-arginine (V-r) to extend the spectrum of activity of glycopeptides to Gram-negative bacteria was investigated. Its MIC towards Escherichia coli, including b-lactamase expressing Ambler classes A, B, and D, was 8 to 16 mg/ml. Addition of 8 times the MIC of V-r to E. coli was acutely bactericidal and associated with a low frequency of resistance (,2.32 × 10210). In vivo, V-r markedly reduced E. coli burden by .7 log10 CFU/g in a thigh muscle model. These data warrant further development of V-r in combatting E. coli, including resistant forms.

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KW - Cationic peptides

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KW - Multidrug resistance

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In vivo targeting of escherichia coli with vancomycin-arginine

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Keywords

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