Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

Abstract

Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum b-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to lowlevel resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem. IntroductionThe traditional first-line available options for treating serious infections caused by enterobacteria include penicillins, cephalosporins, monobactams, carbapenems, fluorquinolones, and in certain situations, aminoglycosides. The frequency of resistance to these first-line agents has been rising worldwide during the last decades [Paterson 2006;Rhomberg and Jones 2009;Houghton et al. 2010;Nordmann, et al. 2011] and now reach high proportions in many areas of the world.

Multidrug-resistant Gram-negative bacteria-resistant infections: epidemiology, clinical issues and therapeutic options

“…b-lactamases are hydrolytic enzymes able to disrupt the b-lactam ring, thus inactivating different classes of b-lactams. 3,4 The most common enzymes in clinical practice are the extended-spectrum-b-lactamases (ESBLs), which are mostly expressed by Enterobacteriaceae. A novel type of class C b-lactamases also showing activity against cefepime and denominated extended spectrum AmpC b-lactamases has been described.…”

“…A novel type of class C b-lactamases also showing activity against cefepime and denominated extended spectrum AmpC b-lactamases has been described. 4 The consequent abuse of carbapenems, representing the first choice for ESBL infections, led to a progressive increase in carbapenem resistance, mainly due to the production of carbapenem-hydrolyzing b-lactamases, or carbapenemases, that usually confer clinical resistance to most b-lactams. 7 Table 1 summarizes the classification of b-lactamases.…”

“…A novel type of class C b-lactamases also showing activity against cefepime and denominated extended spectrum AmpC b-lactamases has been described. 4 The consequent abuse of carbapenems, representing the first choice for ESBL infections, led to a progressive increase in carbapenem resistance, mainly due to the production of carbapenem-hydrolyzing b-lactamases, or carbapenemases, that usually confer clinical resistance to most b-lactams.5,6 K. pneumoniae carbapenemases (KPCs) are the most relevant enzymes among Enterobacteriaceae, and confer resistance to all the blactams, including b-lactam/b-lactamase inhibitors combinations. Class B enzymes, named metallo-b-lactamases are expressed by both enterics and P. aeruginosa and confer resistance to all b-lactams with the exception of aztreonam.…”

Comparación de la prueba tridimensional con PCR múltiple, para detección de carbapenemasas

“…2 Por ello, las infecciones bacterianas a causa de enterobacterias resistentes a carbapenémicos, son de interés tanto desde el punto de vista clínico como en salud pública, debido a que actualmente los carbapenémicos hacen parte de los antibióticos de primera línea de tratamiento para infecciones severas por enterobacterias productoras de betalactamasas de espectro extendido (BLEES). 3 Dada la relevancia del problema para la salud pública, la vigilancia de la RAM es una prioridad a nivel mundial, puesto que permite establecer las medidas de intervención de manera oportuna, así como orientar el tratamiento de los pacientes y definir estrategias para el control de la resistencia; por lo tanto el aumento de infecciones por microorganismos multirresistentes conlleva un reto en la rápida identificación de cepas resistentes, mediante métodos costo efectivos, como las pruebas fenotípicas; que permitan tomar decisiones seguras para los pacientes 4 y que sean una alternativa frente al mayor costo que demandan las pruebas de biología molecular.…”

The New Metall-Beta-Lactamase’s Inhibitor Efficacy in a Model System in Vitro

“…Особого внимания заслуживают металло-бета-лактамазы (МБЛ), наличие которых об-уславливает устойчивость грамотрицательных микроорганизмов ко всем бета-лактамным антибиотикам (в некоторых случаях, кроме аз-треонама) [11,19,25].…”