Evolution and epidemiology of extended-spectrum beta-lactamases (ESBLs) and ESBL-producing microorganisms

The rapid and irrepressible increase in antimicrobial resistance of pathoge nic bacteria that has been observed over the last two decades is widely acc epted to be one of the major problems of human medicine today, Several aspe cts of this situation are especially worrying. There are resistance mechani sms that eliminate the use of last-choice antibiotics in the treatment of v arious kinds of infection. Many resistance mechanisms that emerge and sprea d in bacterial populations are those of wide activity spectra, which compro mise all or a majority of drugs belonging to a given therapeutic group. Som e mechanisms of great clinical importance require specific detection proced ures, as they may not confer clear resistance in vitro on the basis of the interpretive criteria used in standard susceptibility testing. Finally, mul tiple mechanisms affecting the same and/or different groups of antimicrobia ls coexist and are even co-selected in more and more strains of pathogenic bacteria. The variety of beta -lactamases with wide spectra of substrate sp ecificity illustrates very well all the phenomena mentioned above. Being ab le to hydrolyze the majority of beta -lactams that are currently in use, to gether they constitute the most important resistance mechanism of Gram-nega tive rods. Three major groups of these enzymes are usually distinguished, c lass C cephalosporinases (AmpC), extended-spectrum beta -lactamases (ESBLs) and different types of beta -lactamases with carbapenemase activity of whi ch the so-called class B metallo-beta -lactamases (MBLs) are of the greates t concern. This review is focused on various aspects of the evolution and e pidemiology of ESBLs; it does not cover the problems of ESBL detection and clinical relevance of infections caused by ESBL-producing organisms.