β -lactamase-mediated Resistance: A Biochemical, Epidemiological and Genetic Overview

Authors
Gutkind, Gabriel Osvaldo; Di Conza, José Alejandro; Power, Pablo; Radice, Marcela Alejandra
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
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 - lactams (like ampicillin, amoxicillin or cefalexin) provided a favorable scenario for the selection of gram-negative microorganisms producing broad spectrum -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 -lactamases (ESBLs) through point mutations in the existing broad-spectrum -lactamases, such as TEM and SHV enzymes. Overuse of extended-spectrum -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 -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 -lactams including the carbapenems.
Fil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina;
Fil: Di Conza, José Alejandro. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Departamento de Microbiologia General; Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina;
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina;
Fil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina;
Subject
ESBL
CTX-M
AmpC
Carbapenemases
Penicillinases
Cephalosporinases
Broad spectrum lactamases
Extended spectrum lactamases
Inhibitor resistant lactamases
Bioquímica y Biología Molecular
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Farmacología y Farmacia
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/1706