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. 2021 Mar 18;65(4):e02416-20.
doi: 10.1128/AAC.02416-20. Print 2021 Mar 18.

In Vivo Targeting of Escherichia coli with Vancomycin-Arginine

Lewis F Neville  1 , Itamar Shalit  2 , Peter A Warn  3 , Marc H Scheetz  4 , Jiuzhi Sun  5 , Madeline B Chosy  5 , Paul A Wender  5   6 , Lynette Cegelski  5 , Jacob T Rendell  2
Affiliations

In Vivo Targeting of Escherichia coli with Vancomycin-Arginine

Lewis F Neville et al. Antimicrob Agents Chemother. .

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 β-lactamase expressing Ambler classes A, B, and D, was 8 to 16 μg/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 × 10-10). 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: Escherichia coli; Gram-negative bacteria; antibiotic resistance; arginine; cationic peptides; multidrug resistance; vancomycin conjugate.

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Figures

FIG 1
FIG 1
Vancomycin and vancomycin-d-arginine (V-r).
FIG 2
FIG 2
Time-kill of vancomycin-arginine (V-r) and vancomycin against E. coli uropathogens UTI89 and NCTC 13441.
FIG 3
FIG 3
Efficacy of V-r in reducing E. coli UTI89 burden in a 24-h thigh muscle infection model in neutropenic CD-1 mice.
See this image and copyright information in PMC

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