New beta-lactamases: a paradigm for the rapid response of bacterial evolution in the clinical setting

Production of beta-lactamases is one of the most common mechanisms of bacterial resistance to beta-lactam antibiotics. In the clinical setting, the introduction of new classes of beta-lactams has invariably been followed by the emergence of new beta-lactamases capable of degrading them, as a paradigmatic example of rapid bacterial evolution under a rapidly changing selective environment. The scope of this article is to provide an overview on the recent evolution of beta-lactamase-mediated resistance among bacterial pathogens. Focus is on the mechanisms of evolution and dissemination of enzymes of greater clinical impact, including the extended-spectrum beta-lactamases, the AmpC-type beta-lactamases and the carbapenemases, which are currently responsible for emerging resistance to the most recent and powerful beta-lactams (the expanded-spectrum cephalosporins and the carbapenems) among major Gram-negative pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter.