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      Mecanismos de resistencia a carbapenems en P. aeruginosa, Acinetobacter y Enterobacteriaceae y estrategias para su prevención y control Translated title: Resistance mechanisms to carabapenems in P. aeuriginosa, Acinetobacter baumannii and Enterobacteriaceae and strategies for prevention and control

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          Abstract

          La resistencia a carbapenem es un evento poco común, especialmente en miembros de la familia Enterobacteriaceae. Sin embargo, en los últimos años han aumentado los reportes de cepas de Enterobacteriaceae resistentes a carbapenem. Por otro lado, la resistencia a carbapenem es más frecuente en Pseudomonas aeruginosa y Acinetobacter baumannii. Las investigaciones han demostrado que para adquirir resistencia a los carbapenem se requiere de la combinación de varios mecanismos de resistencia. La combinación más importante reportada hasta el momento ha sido la producción de una ß-lactamasa junto a la disminución de la permeabilidad de la membrana externa por la pérdida de porinas. Las ß-lactamasas implicadas en la resistencia han sido principalmente AmpC y carbapenemasas. Las estrategias actuales para el control de la resistencia dentro de los hospitales siguen basandose en la estricta implementación de las barreras de contacto y el lavado de manos junto con el uso adecuado de los antibióticos disponibles.

          Translated abstract

          Resistance to carbapenems is rare, particularly among members of the Enterobacteriaceae family. However, over the last years, reports of Enterobacteriaceae strains resistant to carbapenems have increased. On the other hand, carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii is much more frequent. Research on the topic has demonstrated that to acquire carbapenem resistance, a combination of various resistance mechanisms is needed. The most important combination described to date has been the production of a ß-lactamase together with a decreased permeability through the outer membrane secondary to the loss of porins. The ß-lactamases involved in this resistance have been mainly the AmpC type ß-lactamases and the carbapenemases. Current strategies for resistance control within hospitals are still based on a strict implementation of contact barriers and hand washing associated with a correct use of the available antibiotics.

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          Most cited references54

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          Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare?

          Pseudomonas aeruginosa carries multiresistance plasmids less often than does Klebsiella pneumoniae, develops mutational resistance to cephalosporins less readily than Enterobacter species, and has less inherent resistance than Stenotrophomonas maltophilia. What nevertheless makes P. aeruginosa uniquely problematic is a combination of the following: the species' inherent resistance to many drug classes; its ability to acquire resistance, via mutations, to all relevant treatments; its high and increasing rates of resistance locally; and its frequent role in serious infections. A few isolates of P. aeruginosa are resistant to all reliable antibiotics, and this problem seems likely to grow with the emergence of integrins that carry gene cassettes encoding both carbapenemases and amikacin acetyltransferases.
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            Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae.

            A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 microg/ml. The beta-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three beta-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla(SHV) and bla(TEM) genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies with Escherichia coli showed that the beta-lactamase with a pI of 6.7, KPC-1 (K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene, bla(KPC-1), was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing beta-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing beta-lactamase, Sme-1, from Serratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing beta-lactamase, KPC-1, although alterations in porin expression may also play a role.
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              Emerging carbapenemases in Gram-negative aerobes.

              Carbapenemases may be defined as beta-lactamases that significantly hydrolyze at least imipenem or/and meropenem. Carbapenemases involved in acquired resistance are of Ambler molecular classes A, B, and D. Class A, clavulanic acid-inhibited carbapenemases are rare. They are either chromosomally encoded (NMC-A, Sme-1 to Sme-3, IMI-1) in Enterobacter cloacae and Serratia marcescens, or plasmid encoded, such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa, the latter being a point-mutant of the clavulanic acid-inhibited extended-spectrum beta-lactamase GES-1. The class B enzymes are the most clinically significant carbapenemases. They are metalloenzymes of the IMP or VIM series. They have been reported worldwide but mostly from South East Asia and Europe. Metalloenzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. Finally, the class D carbapenemases are increasingly reported in Acinetobacter baumannii but compromise imipenem and meropenem susceptibility only marginally. The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to the spread of plasmid- or integron-borne genes. Because most of these carbapenemases confer only reduced susceptibility to carbapenems in Enterobacteriaceae, they may remain underestimated as a consequence of the lack of their detection.
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                Author and article information

                Journal
                inf
                Infectio
                Infect.
                Asociación Colombiana de Infectología. (Bogotá, Distrito Capital, Colombia )
                0123-9392
                June 2006
                : 10
                : 2
                : 85-93
                Affiliations
                [01] Cali orgnameCentro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM Colombia
                Article
                S0123-93922006000200006 S0123-9392(06)01000206
                4590e8bf-907d-402b-b547-d3bf881ebc67

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 25 April 2004
                : 21 December 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 54, Pages: 9
                Product

                SciELO Colombia

                Self URI: Texto completo solamente en formato PDF (ES)
                Categories
                Artículo de revisión

                Enterobacteriaceae,Acinetobacter baumannii,Pseudomonas aeruginosa,ß-lactams,carbapenemases,bacterial resistance,carbapenems,ß -lactámicos,carbapenemasas,carbapenem, resistencia bacteriana

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