Abstract
The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors to be used in conjunction with carbapenems and other β-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-β-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.
Keywords:
NDM-1; VIM-2; antibiotic resistance; efficacy; meropenem; metallo-β-lactamase inhibitor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / pharmacology*
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Carbapenem-Resistant Enterobacteriaceae / drug effects*
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Carbapenems / pharmacology
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Crystallography, X-Ray
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Drug Resistance, Multiple, Bacterial*
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Enterobacteriaceae Infections / drug therapy*
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Inhibitory Concentration 50
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Meropenem / pharmacology
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Microbial Sensitivity Tests
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Picolinic Acids / chemistry
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Picolinic Acids / pharmacology
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Protein Binding
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Structure-Activity Relationship
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beta-Lactamase Inhibitors / chemistry*
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beta-Lactamase Inhibitors / pharmacology
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beta-Lactamases
Substances
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Anti-Bacterial Agents
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Carbapenems
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Picolinic Acids
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beta-Lactamase Inhibitors
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beta-Lactamases
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Meropenem
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picolinic acid