Extended-spectrum beta-lactamases: definition, history, an update on their genetic environment and detection methods

Bacterial resistance remains a major challenge in the therapeutic field. Beta-lactam antibiotics are widely used to treat Enterobacteriaceae, especially third-generation cephalosporins (3GCs), which are used in infections caused by bacteria resistant to first- and second-line antibiotics. However, these bacteria have been able to develop resistance against the used antibiotics through the production of extended-spectrum beta-lactamase (ESBL) enzymes. These enzymes inactivate 3GCs and are sensitive to beta-lactamase inhibitors such as clavulanic acid. This resistance is acquired by plasmids (IncF, IncI, IncK…) which carry mobile genetic elements (insertion sequence, transposon…) with genes coding for these enzymes, namely, the bla _CTX-M, bla _SHV and bla _TEM, which code for the most frequent types of ESBL (CTX-M, SHV and TEM). Unfortunately, when ESBLs are not identified in time, appropriate treatment is delayed, reducing the chances of cure. Current data highlight the spread and dangerousness of ESBL-producing bacteria worldwide and confirm the priority given to these bacteria by the World Health Organization, which insists on vigilance in identifying them, both in patients and through surveillance studies. The aim of the current review is to provide a better understanding of ESBLs, to highlight their historical evolution and to show the importance of their genetic environment in the dissemination and spread of these enzymes worldwide, as well as the techniques used to detect them in laboratory studies. Current data demonstrate the degree of danger posed by ESBL-producing bacteria and confirm the priority given to these bacteria by the World Health Organization for the development of new antimicrobial agents.