The ongoing emergence of bacterial strains resistant to even third- and fourth-generation β-lactam antibiotics is
one of the most pressing and challenging issues in clinical therapy. Furthermore, under the pressure of antibiotics used
ubiquitously over the last 80 years, functional mutations and new resistances are continuously increasing. Therefore, new
drugs and new approaches to the infections produced by multidrug-resistant Gram-negative bacteria are categorically necessary
and expected by the scientific community. This review describes the most deleterious known extended-spectrum β-
lactamases and the molecules now available for targeting bacterial infections. The active-site chemical and geometric
properties that are potentially exploitable for the design of both broad-spectrum and selective compounds are described.
Keywords: β-lactam antibiotics, β-lactamase binding site, β-lactamase inhibitors, carbapenemase, extended spectrum β-
lactamases, molecular interaction fields, resistance.
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