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 journalArticlepeer-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 languageEnglish
Article numbere02416-20
JournalAntimicrobial Agents and Chemotherapy
Volume65
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

Funding

FundersFunder number
SuperTrans Medical
National Science FoundationCHE-1566423
National Institutes of HealthNIH-CA031845
National Institute of General Medical SciencesR01GM117278
Stanford University

    Keywords

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

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