Early after the introduction of the first (narrow spectrum) penicillins into clinical use, penicillinase-producing staphylococci
replaced (worldwide) the previously susceptible microorganisms. Similarly, the extensive use of broad-spectrum, orally administered β-
lactams (like ampicillin, amoxicillin or cefalexin) provided a favorable scenario for the selection of gram-negative microorganisms producing
broad spectrum β-lactamases almost 45 years ago. These microorganisms could be controlled by the introduction of the so called
“extended spectrum cephalosporins”. However, overuse of these drugs resulted, after a few years, in the emergence of extended-spectrum
β-lactamases (ESBLs) through point mutations in the existing broad-spectrum β-lactamases, such as TEM and SHV enzymes. Overuse of
extended-spectrum β-lactams also gave rise to chromosomal mutations in regulatory genes which resulted in the overproduction of chromosomal
AmpC genes, and, in other regions of the world, in the explosive emergence of other ESBL families, like the CTX-Ms. Carbapenems
remained active on microorganisms harboring these extended-spectrum β-lactamases, while both carbapenems and fourth generation
cephalosporins remained active towards those with derepressed (or the more recent plasmidic) AmpCs. However, microorganisms
countered this assault by the emergence of the so called carbapenemases (both serine- and metallo- enzymes) which, in some cases, are
actually capable of hydrolyzing almost all β-lactams including the carbapenems.
Although all these enzyme families (some of them represented by hundreds of members) are for sure pre-dating the antibiotic era in environmental
and clinically significant microorganisms, it was the misuse of these antibiotics that drove their evolution. This paper describes
in detail each major class of β-lactamase including epidemiology, genetic, and biochemical evaluations.