Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios

Among Bacteroides fragilis group, Bacteroides fragilis constitutes the most frequently recovered specie in clinical specimens, partially because it is the most virulent specie of the group.\nMost of B. fragilis isolates result resistant to ?-lactam antibiotics, except carbapenems, being production o...

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Autor principal: Litterio, Mirta Rosa
Otros Autores: Cejas, Daniela
Formato: Tesis de maestría acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2016
Materias:
cfiA
Anaerobios
Metalobeta Lactamasa
Bacteroides fagilis
B-Lactamasas
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1918
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1918.dir/1918.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-HWA_1918
record_format dspace
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic cfiA
Anaerobios
Metalobeta Lactamasa
Bacteroides fagilis
B-Lactamasas
Ciencias de la vida
spellingShingle cfiA
Anaerobios
Metalobeta Lactamasa
Bacteroides fagilis
B-Lactamasas
Ciencias de la vida
Litterio, Mirta Rosa
Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
topic_facet cfiA
Anaerobios
Metalobeta Lactamasa
Bacteroides fagilis
B-Lactamasas
Ciencias de la vida
description Among Bacteroides fragilis group, Bacteroides fragilis constitutes the most frequently recovered specie in clinical specimens, partially because it is the most virulent specie of the group.\nMost of B. fragilis isolates result resistant to ?-lactam antibiotics, except carbapenems, being production of ?-lactamases the principal resistance mechanism. Three different ?-lactamases have been described in B. fragilis: - CepA, an endogenous cephalosporinase conferring resistance to the majority of the ?-lactam antibiotics with the exception of cephamycins,and carbapenems, and that is inhibited by ?-lactamase inhibitors. - CfxA which confers resistance to cephaloridine, cefoxitin, and others ?-lactams with the exception of imipenem. And CfiA, a metallo-?-lactamase which is active against penicilins, cephalosporins, including cephamycins, and carbapenems. CfiA is neither inhibited by clavulanic acid nor sulbactam. EDTA is a good inhibitor of CfiA and its activity could be recovered by the addition of Zn2+.\nThe activity of antimicrobial agents against Bacteroides fragilis group isolates remained unchanged through different survey studies performed in our country. However, in a surveillance study conducted between 2006 and 2009, 3 clinical isolates of gram negative rods of this group displaying high level resistance (CIM?32 ?g/ml) to carbapenems were detected.\nThis finding was the first report in our country in isolates of B. fragilis from clinical materials.\nThe presence of a metallo-?-lactamase in those isolates was suspected from inhibition tests with EDTA. The overall objective of this study was to analyze the presence of cfiA resistance marker in isolates recovered during the study previously mentioned and to analyze the genetic environment of this marker.\nThis is the first study in Argentina, in which 7 isolates of B. fragilis carring cfiA strains are informed. Three of them correspond to those isolates that showed high level resistance to carbapenems (CIM?32 ?g/ml). In 2/3 CfiA13 was identify and its coding gene was associated to an IS corresponding to IS1380 family, IS942 group. In the other resistant isolate CfiA4 was identified and its coding genes was associated to an IS belonging to family IS21 family.\nIn the 4 imipenem susceptible strains CfiA4, CfiA2 and two new variants related to CfiA4 and CfiA13 were identified. No IS elements were found upstream their coding genes. Promoter sequences -10 and -35 adjacent upstream cfiA2 were only identified in the doripenem intermediate isolate
author2 Cejas, Daniela
author_facet Cejas, Daniela
Litterio, Mirta Rosa
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Litterio, Mirta Rosa
author_sort Litterio, Mirta Rosa
title Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
title_short Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
title_full Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
title_fullStr Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
title_full_unstemmed Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
title_sort detección del determinante genético (cfia) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios
publisher Facultad de Farmacia y Bioquímica
publishDate 2016
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1918
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1918.dir/1918.PDF
work_keys_str_mv AT litteriomirtarosa detecciondeldeterminantegeneticocfiadelaresistenciaacarbapenemsysuentornomolecularenaislamientosclinicosdebacilosgramnegativosanaerobios
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spelling I28-R145-HWA_19182019-09-27 Among Bacteroides fragilis group, Bacteroides fragilis constitutes the most frequently recovered specie in clinical specimens, partially because it is the most virulent specie of the group.\nMost of B. fragilis isolates result resistant to ?-lactam antibiotics, except carbapenems, being production of ?-lactamases the principal resistance mechanism. Three different ?-lactamases have been described in B. fragilis: - CepA, an endogenous cephalosporinase conferring resistance to the majority of the ?-lactam antibiotics with the exception of cephamycins,and carbapenems, and that is inhibited by ?-lactamase inhibitors. - CfxA which confers resistance to cephaloridine, cefoxitin, and others ?-lactams with the exception of imipenem. And CfiA, a metallo-?-lactamase which is active against penicilins, cephalosporins, including cephamycins, and carbapenems. CfiA is neither inhibited by clavulanic acid nor sulbactam. EDTA is a good inhibitor of CfiA and its activity could be recovered by the addition of Zn2+.\nThe activity of antimicrobial agents against Bacteroides fragilis group isolates remained unchanged through different survey studies performed in our country. However, in a surveillance study conducted between 2006 and 2009, 3 clinical isolates of gram negative rods of this group displaying high level resistance (CIM?32 ?g/ml) to carbapenems were detected.\nThis finding was the first report in our country in isolates of B. fragilis from clinical materials.\nThe presence of a metallo-?-lactamase in those isolates was suspected from inhibition tests with EDTA. The overall objective of this study was to analyze the presence of cfiA resistance marker in isolates recovered during the study previously mentioned and to analyze the genetic environment of this marker.\nThis is the first study in Argentina, in which 7 isolates of B. fragilis carring cfiA strains are informed. Three of them correspond to those isolates that showed high level resistance to carbapenems (CIM?32 ?g/ml). In 2/3 CfiA13 was identify and its coding gene was associated to an IS corresponding to IS1380 family, IS942 group. In the other resistant isolate CfiA4 was identified and its coding genes was associated to an IS belonging to family IS21 family.\nIn the 4 imipenem susceptible strains CfiA4, CfiA2 and two new variants related to CfiA4 and CfiA13 were identified. No IS elements were found upstream their coding genes. Promoter sequences -10 and -35 adjacent upstream cfiA2 were only identified in the doripenem intermediate isolate Fil: Litterio, Mirta Rosa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Cejas, Daniela Facultad de Farmacia y Bioquímica Radice, Marcela Litterio, Mirta Rosa 2016-07-29 Bacteroides fragilis es la especie del grupo Bacteroides fragilis que se asila con mayor frecuencia de especímenes clínicos, debido, en parte, a que es la especie más virulenta del grupo.\nLa mayoría de los aislamientos de B. fragilis resultan resistentes a los antibióticos ?-lactámicos, excepto a los carbapenems, siendo el principal mecanismo de resistencia la producción de ?-lactamasas. En B. fragilis se han descripto 3 ?-lactamasas diferentes: - CepA, una cefalosporinasa endógena que le confiere resistencia a la mayoría de los antibióticos ?-lactámicos con excepción de las cefamicinas y carbapenems, y es inhibida por los inhibidores de ?-lactamasas. - CfxA la cual confiere resistencia a cefaloridina, cefoxitina y otros antibióticos ?-lactámicos excepto imipenem. Y una metalo-?-lactamasa CfiA con actividad frente a penicilinas, cefalosporinas, incluyendo las cefamicinas, y carbapenems. CfiA no es inhibida por el ácido clavulánico ni el sulbactam pero sí por EDTA y su actividad se recupera por el agregado de Zn2+.\nEn nuestro país, la actividad de los antimicrobianos frente a los aislamientos del grupo Bacteroides fragilis se ha mantenido inalterable a lo largo de diferentes relevamientos efectuados. Sin embargo en un estudio de vigilancia llevado a cabo entre los años 2006 y el 2009, en 363 aislamientos clínicos de bacilos gram negativos anaerobios pertenecientes a este grupo, se detectaron 3 aislamientos con alto nivel de resistencia (CIM?32 ?g/ml) a los carbapenems.\nEste hallazgo constituyó el primer reporte en nuestro país en aislamientos de B.\nfragilis procedentes de materiales clínicos.\nEn dichos aislamientos la presencia de una metalo-?-lactamasa fue\nsospechada a partir de ensayos de inhibición con EDTA\nEl objetivo general de este trabajo fue analizar la presencia del marcador de\nresistencia cfiA en aislamientos de B. fragilis recuperados durante el estudio de\nvigilancia mencionado previamente, así como analizar el entorno genético de\ndicho marcador.\nEste es el primer estudio en Argentina donde se informan 7 aislamientos de B.\nfragilis portadores de cfiA. Tres de ellos correspondieron a los aislamientos que\npresentaban resistencia a carbapenemes (CIM?32 ?g/ml). En 2/3 se identificó\nal gen codificante de CfiA13 asociado a IS pertenecientes a la familia IS1380,\ngrupo IS942. En el restante aislamiento resistente se identificó al gen\ncodificante de CfiA4 asociado a una IS perteneciente a la familia IS21.\nEn los 4 aislamientos sensibles a imipenem se identificaron las variantes CfiA\n4, CfiA 2 y dos nuevas variantes, de CfiA4 y CfiA13. No se hallaron IS en la\nregión upstream a los genes codificantes. Solo en el aislamiento que resultó\nintermedio para doripenem se identificaron las secuencias promotoras -10 y -35\nen la región adyacente a cfiA2. application/pdf Almuzara, Marisa Basualdo Farjat, Juan Ángel Smayevsky, Jorgelina cfiA Anaerobios Metalobeta Lactamasa Bacteroides fagilis B-Lactamasas spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Detección del determinante genético (cfiA) de la resistencia a carbapenems y su entorno molecular en aislamientos clínicos de bacilos gram negativos anaerobios info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1918 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1918.dir/1918.PDF

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