20–22 The KPC enzymes exhibit universal distribution, and generically hydrolyze carbapenems, penicillins, cephalosporins and monobactams. The class A beta-lactamases with carbapenemase activity are mainly represented by the KPC family, and to a lesser extent by GES (not all their variants possess carbapenemase activity), SME, IMI and other variants. 14 The class C enzymes can degrade penicillins and cephalosporins such as cefotaxime and ceftazidime, and although they do not hydrolyze carbapenems effectively (with some exceptions, such as CMY-10 or ACT-28), when the enzyme is hyper-produced in strains with additional mechanisms (see below), clinically important resistance levels can be reached. 15 The level of resistance of the microorganism to each beta-lactam depends on the amount of enzyme (beta-lactam induction capacity or enzyme derepression state) and the resistance of each compound to enzyme hydrolysis. 18 Most plasmidic cephamycinases are produced at a high level. 16,17 Mutations in regulator genes 17 can condition high-level production of enzyme even if there is no inducing beta-lactam the corresponding strains are therefore referred to as derepressed strains. Basal conditions are characterized by a low production of AmpC (repression state), though certain beta-lactams are more or less effective in inducing the production of the enzyme, and when the compound disappears, such induction ceases. coli), the production of chromosomal AmpC is regulated by a complex system of genes. ![]() 15 As a norm, they are not inhibited by clavulanic acid (neither tazobactam nor sulbactam), but are susceptible to new inhibitors such as avibactam. The class C beta-lactamases include both AmpC enzymes coded for by chromosomal genes 14 and variants coded for by plasmids (plasmidic cephamycinases). 6,7 From the clinical perspective, the enzymes of greatest interest in enterobacteria correspond to three groups: ESBL, class C enzymes and carbapenemases. 5 On the other hand, the beta-lactamases can be classified into three functional groups (1, 2 and 3) according to their capacity to hydrolyze different substrates and their inhibition by different compounds ( Table 1). 4 The enzyme activity depends on a serine group in classes A, C and D, and on one or two zinc ions in class B as a result, the latter are also known as metallo-β-lactamases. 2,3 Four classes of beta-lactamases have been established, based on their molecular structure (A, B, C and D). The principal mechanism of resistance to beta-lactams in Enterobacterales is the production of beta-lactamases – enzymes that hydrolyze the beta-lactam ring, inhibiting its antibacterial activity. Enterobacterales Resistance to betalactams baumannii and also Stenotrophomonas maltophilia. The present study provides a succinct review of the principal mechanisms of resistance of Enterobacterales, P. 1 Moreover, these microorganisms usually present resistance to other groups/families of antimicrobials commonly used in clinical practice. In this context, a critical concern refers to Enterobacterales resistant to carbapenems or producing extended-spectrum beta-lactamase (ESBL) and non-fermenting species ( Pseudomonas aeruginosa, Acinetobacter baumannii) resistant to carbapenems. The World Health Organization (WHO) has published a list of priorities referred to bacteria for which the development of new antimicrobials is an urgent need. Resistance to antimicrobials is one of the main healthcare problems worldwide, particularly in relation to multiresistant microorganisms. Se presentará información actualizada sobre la importancia en la resistencia de mecanismos de modificación de antimicrobianos (incluyendo betalactamasas de clase C de espectro extendido, carbapenemasas y enzimas modificadoras de aminoglucósidos), alteraciones de la permeabilidad por trastornos en la expresión de porinas o del lipopolisacárido, producción de bombas de expulsión activa, alteraciones de la diana o protección de la misma y expresión de sistemas de doble componente. ![]() En esta revisión se abordarán los principales mecanismos de resistencia de los Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii y Stenotrophomonas maltophilia a betalactámicos, quinolonas, aminoglucósidos y polimixinas. Los Enterobacterales resistentes a carbapenémicos o productores de betalactamasas de espectro extendido (BLEE) y los no fermentadores resistentes a carbapenémicos presentan resistencia a muchos de los antimicrobianos comúnmente empleados en la práctica clínica, y han sido reconocidos por la Organización Mundial de la Salud como una prioridad crítica para el desarrollo de nuevos antimicrobianos.
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