El problema creciente de la resistencia antibiótica en bacilos gramnegativos: situación actualThe growing problem of antibiotic resistance in clinically relevant Gram-negative bacteria: current situation

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Resumen

La resistencia a los antimicrobianos en bacterias gramnegativas de importancia clínica es un problema creciente, que en los últimos años ha sobrepasado la barrera nosocomial para afectar también a pacientes no hospitalizados. En enterobacterias, los principales aspectos de esta situación incluyen la resistencia a β-lactámicos (causada por β-lactamasas intrínsecas, β-lactamasas de espectro extendido, cefamicinasas plasmídicas y carbapenemasas, en especial cuando se producen en cepas con trastornos de la permeabilidad por alteraciones en porinas), y la resistencia a quinolonas, un problema multifactorial en el que se está reconociendo la importancia de los mecanismos mediados por plásmidos (proteínas Qnr, acetilasa, bombas de expulsión). Varios estudios en España y en otros países indican que las cepas con estos mecanismos están creciendo, siendo particularmente preocupante la expansión de cepas de Escherichia coli y de otras especies que producen β-lactamasas de espectro extendido (sobre todo de la familia CTX-M), que afectan a pacientes de la comunidad. Es cada vez más frecuente que estos mecanismos no se observen de forma aislada, sino combinados en una misma cepa, lo que conduce a la multirresistencia. Este problema es también de gran trascendencia clínica en diversos bacilos gramnegativos no fermentadores, incluyendo Pseudomonas aeruginosa y Acinetobacter baumannii, y en menor medida Stenotrophomonas maltophilia y algunas otras especies. En este último grupo de microorganismos la multirresistencia es consecuencia de la presencia de mecanismos intrínsecos (producción de distintos tipos de β-lactamasas, baja permeabilidad y expresión de bombas de expulsión activa) y de la adquisición de genes exógenos. Las dificultades terapéuticas llegan a su extremo en casos de resistencia a carbapenems (de causa multifactorial) y a polimixinas. Es necesario desarrollar nuevos compuestos con actividad frente a bacilos gramnegativos multirresistentes que, junto con otras medidas, ayuden a controlar la grave situación actualmente existente.

Abstract

Resistance to antimicrobial agents in clinically relevant Gram-negative bacteria is an increasingly important problem, which in the last few years has spread from the hospital setting to the community. In enterobacteria, the main features of this situation include resistance to β-lactams and quinolones. β-Lactam resistance is caused by intrinsic β-lactamases, extended-spectrum β-lactamases, plasmid-mediated cephamycinases and carbapenemses, particularly when produced in strains with decreased permeability because of altered porin expression. Quinolone resistance is a multifactorial problem in which the importance of plasmid-mediated mechanisms (Qnr proteins, acetylase, active efflux pumps) is being recognized. Several studies in Spain and other countries show that strains with these resistance mechanisms are being isolated with increased frequency. Of particular concern is the spread of Escherichia coli and other species producing extended-spectrum β-lactamases (most frequently of the CTX-M family), affecting outpatients. Very commonly these mechanisms are simultaneously expressed within the same bacterial host, leading to a multiresistance phenotype. This problem is also of major clinical importance in non-fermenting Gramnegative rods, including Pseudomonas aeruginosa and Acinetobacter baumannii and, to a lesser extent, Stenotrophomonas maltophilia and some other species. Multiresistance in non-fermenting organisms results from the presence of intrinsic mechanisms (production of distinct β-lactamases, decreased permeability and expression of several active efflux pumps) and from the acquisition of exogenous genes. Therapeutic difficulties reach their maximum when bacteria express resistance to carbapenems (a multifactorial problem) or to polymyxins. New compounds with specific activity against multiresistant Gram-negative rods should be developed, which, together with other measures, would contribute to controlling the current serious situation.

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