{"id":114649,"date":"2018-03-11T10:42:46","date_gmt":"2018-03-11T10:42:46","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-mecanismos-de-resistencia-a-fluoroquinolonas-de-localizacion-plasma%c2%addica-en-aislamientos-cla%c2%adnicos-de-enterobacterias-en-la-region-de-murcia\/"},"modified":"2018-03-11T10:42:46","modified_gmt":"2018-03-11T10:42:46","slug":"estudio-de-mecanismos-de-resistencia-a-fluoroquinolonas-de-localizacion-plasma%c2%addica-en-aislamientos-cla%c2%adnicos-de-enterobacterias-en-la-region-de-murcia","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/microbiologia-clinica\/estudio-de-mecanismos-de-resistencia-a-fluoroquinolonas-de-localizacion-plasma%c2%addica-en-aislamientos-cla%c2%adnicos-de-enterobacterias-en-la-region-de-murcia\/","title":{"rendered":"Estudio de mecanismos de resistencia a fluoroquinolonas de localizaci\u00f3n plasm\u00eddica en aislamientos cl\u00ednicos de enterobacterias en la regi\u00f3n de murcia"},"content":{"rendered":"

Tesis doctoral de Miriam Albert Hernandez <\/strong><\/h2>\n

Objectivos: el principal objectivo de este estudio fue conocer la preValencia de los mecanismos pl\u00e1smidicos de resistencia a fluoroquinolonas (rpfqs) en aislamientos cl\u00ednicos de enterobacterias tanto productoras como no productoras de ?-Lactamasas de espectro extendido (blees) en la regi\u00f3n de murcia. metodolog\u00eda: se estudiaron 312 aislamientos cl\u00ednicos de enterobacterias consecutivos, no duplicados obtenidos en el servicio de microbiolog\u00eda del hospital universitario virgen de la arrixaca de murcia durante noviembre y diciembre de 2010. Los genes qnra, qnrb, qnrc, qnrs, qepa y aac (6') ib-cr fueron amplificados mediante pcr. Las blees fueron caracterizadas mediante pcr y secuenciaci\u00f3n del adn. En todos los aislamientos portadores de genes de rpfqs se estudiaron mutaciones en la qrdr de los genes gyra, gyrb, parc y pare. La relaci\u00f3n clonal entre los aislamientos con genes de rpfqs se evalu\u00f3 mediante rep-pcr y rflp-pfge. Se realizaron experimentos de selecci\u00f3n in vitro de mutantes resistentes a fluoroquinolonas de primer y segundo escal\u00f3n en aislamientos portadores de determinantes de rpfqs pero sin mutaciones en los genes de las topoisomerasas. resultados: un 11.2% (35\/312) de los aislamientos fueron productores de blees. Ctx-m-14 fue el tipo de blee m\u00e1s frecuente (14\/35 aislamientos, 40%). Los mecanismos de rpfqs se detectaron en 20 aislamientos (6.4%) (9 e.Coli, 5 k. Pneumoniae, 2 c. Freundii, 3 e. Cloacae y 1 s. Enteritidis), y fueron claramente m\u00e1s prevalentes en aislamientos productores de blees (28.6% vs. 3.6%). Un 65% de los aislamientos fueron portadores de genes qnr como \u00fanico mecanismo de rpfqs, en 3 aislamientos (15%) se detect\u00f3 aac(6')-ib-cr y 4 aislamientos presentaron genes qnr y aac(6')-ib-cr combinados. Las enterobacterias no productoras de blees fueron portadoras siempre de genes qnr, mientras que en los aislamientos productores de blees, se detect\u00f3 aac(6')-ib-cr en 7 de 10 aislamientos (70%), s\u00f3lo o combinado con genes qnr. Las dos cepas de k. Pneumoniae portadoras de genes aac(6')-ib-cr y qnr en ausencia de mutaciones en las topoisomerasas, fueron resistentes a ciprofloxacino. Un 45% (9\/20) de los aislamientos con genes de rpfqs mostraron mutaciones en las topoisomerasas y un 55% de ellos acumul\u00f3 4 o m\u00e1s mutaciones. El estudio de relaci\u00f3n clonal entre los aislamientos portadores de determinantes de rpfqs mostr\u00f3 diferentes patrones de bandas de adn en la mayor\u00eda de ellos, indicando que no estaban relacionados clonalmente. Sin embargo, 3 cepas de e. Coli mostraron id\u00e9nticos patrones de bandas, portaban el mismo perfil de mutaciones en las topoisomeras pero diferente mecanismo de rpfqs y diferentes blee. La frecuencia de selecci\u00f3n de mutantes a ciprofloxacino fue de 1.4×10-6 a 2.2×10-8. No se detectaron mutaciones en las topoisomerasas en los aislamientos seleccionados portadores de genes de rpfqs pero se observ\u00f3 un incremento significativo en los valores de cmi de ciprofloxacino (de 4 a 128 veces) y de ofloxacino (de 16 a 256 veces). conclusiones: los determinantes de rpfqs son mucho m\u00e1s frecuentes en enterobacterias productoras de blees (28.6% vs. 3.6%) pero con diferentes caracter\u00edsticas. Las productoras de blees y portadoras de genes de rpfqs se localizan en la mayor\u00eda de casos en las especies de e. Coli or k.Pneumoniae portando determinantes qnr y\/o aac(6')-ib-cr, m\u00faltiples mutaciones en los genes de las topoisomerasas y elevadas cmis de ciprofloxacino. Sin embargo, los determinantes de rpfqs en ausencia de blees aparecen en un grupo de especies m\u00e1s heterog\u00e9neo, los determinantes qnr son predominantes, las mutaciones en los genes de las topoisomerasas son infrecuentes (aparecen s\u00f3lo en e. Coli) y son normalmente sensibles a ciprofloxacino. Los determinantes de rpfqs no conducen a resistencia a fluoroquinolonas de alto nivel por s\u00ed mismos, pero la asociaci\u00f3n de dos determinantes de rpfqs diferentes en el mismo aislamientos podr\u00eda derivar en ella. objectives: the main objective of this study was to know the prevalence of plasmid-mediated quinolone-resistance (pmqr) in extended-spectrum ?-Lactamases (esbl)-non-producing enterobacteria clinical isolates obtained in murcia (spain), and determine the differences with esbl-producing enterobacteria. methods: we studied 312 consecutive, non-duplicated enterobacteria clinical isolates, obtained in the department of microbiology of university hospital virgen de la arrixaca of murcia during november and december 2010. Qnra, qnrb, qnrc, qnrs, qepa and aac (6') ib-cr genes were amplified by pcr. Esbls were characterized by pcr and dna sequencing. Mutations in the gyra, gyrb, parc and pare genes qrdr were studied in pmqr-positive isolates. Clonal proximity among pmqr-positive isolates was evaluated by rep-pcr and rflp-pfge. First and second-step in vitro selection of fluoroquinolone-resistant mutants experiments were performed in pmqr-positive isolates with no mutations in topoisomerases genes. results: thirty-five isolates (11.2%) were esbl-producers. Ctx-m-14 was the most frequent esbl (14\/35 isolates, 40%). Pmqr mechanisms were detected in 20 isolates (6.4%) (9 e.Coli, 5 k. Pneumoniae, 2 c. Freundii, 3 e. Cloacae y 1 s. Enteritidis), and were clearly more prevalent in esbl-producing isolates (28.6% vs. 3.6%). Thirteen isolates (65%) harbored qnr genes as the only pmqr mechanism, 3 isolates (15%) harbored aac(6')-ib-cr and 4 isolates combined qnr and aac(6')-ib-cr genes. Esbl-non producing enterobacteria harbored always qnr genes, while esbl-producing isolates, harboured aac(6')-ib-cr in 7 out of 10 isolates (70%), alone or combined to qnr genes. The two k. Pneumoniae isolates combining aac(6')-ib-cr and qnr genes in absence of topoisomerases mutations, were shown ciprofloxacin-resistant. Nine (45%) pmqr-positive isolates showed topoisomerases mutations. 55% of them accumulated 4 or more topoisomerase mutations. Clonal relatedness study among the pmqr-positive isolates showed different dna patterns in most isolates, indicating that they were not clonally related. However, three e. Coli isolates showed identical dna patterns, harboring the same topoisomerase mutations profile but different pqmr mechanism and esbls presence. Ciprofloxacin-mutants selection frequency was from 1.4×10-6 to 2.2×10-8. Topoisomerases mutations were absent after fluoroquinolone selection from pmqr-positive strains but it was observed a significant increase in quinolones mics (4 to 128-fold for ciprofloxacin and 16 to 256-fold for ofloxacin). conclusions: pmqr determinants are much more frequent in esbl-producing enterobacteria (28.6% vs. 3.6%) but with different features. Pmqr-, esbl-harboring enterobacteria are in most cases e. Coli or k.Pneumoniae harboring qnr and\/or aac(6')-ib-cr determinants, multiple topoisomerase genes mutations and high mics of ciprofloxacin. Meanwhile, pmqr determinants in absence of esbls appear in a more heterogeneous group of species, qnr determinants are largely predominant, topoisomerases genes mutations are infrequent (appear only in e. Coli) and are usually ciprofloxacin-susceptible. Pmqr determinants do not lead to fluoroquinolone resistance by themselves, but two different pmqr determinants combined in the same isolate might do it.<\/p>\n

 <\/p>\n

Datos acad\u00e9micos de la tesis doctoral \u00abEstudio de mecanismos de resistencia a fluoroquinolonas de localizaci\u00f3n plasm\u00eddica en aislamientos cl\u00ednicos de enterobacterias en la regi\u00f3n de murcia<\/strong>\u00ab<\/h3>\n
    \n
  • T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de mecanismos de resistencia a fluoroquinolonas de localizaci\u00f3n plasm\u00eddica en aislamientos cl\u00ednicos de enterobacterias en la regi\u00f3n de murcia <\/li>\n
  • Autor:<\/strong>\u00a0 Miriam Albert Hernandez <\/li>\n
  • Universidad:<\/strong>\u00a0 Murcia<\/li>\n
  • Fecha de lectura de la tesis:<\/strong>\u00a0 18\/09\/2013<\/li>\n<\/ul>\n

     <\/p>\n

    Direcci\u00f3n y tribunal<\/h3>\n
      \n
    • Director de la tesis<\/strong>\n
        \n
      • Manuel Segovia Hernandez<\/li>\n<\/ul>\n<\/li>\n
      • Tribunal<\/strong>\n
          \n
        • Presidente del tribunal: Jos\u00e9 angel Garc\u00eda rodr\u00edguez <\/li>\n
        • carme Salvador garcia (vocal)<\/li>\n
        • Juan Luis Mu\u00f1oz bellido (vocal)<\/li>\n
        • Antonio c\u00e1ndido G\u00f3mez Garc\u00eda (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n

           <\/p>\n","protected":false},"excerpt":{"rendered":"

          Tesis doctoral de Miriam Albert Hernandez Objectivos: el principal objectivo de este estudio fue conocer la preValencia de los mecanismos […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[597,8235],"tags":[9630,214710,9876,25841,3373,227172],"class_list":["post-114649","post","type-post","status-publish","format-standard","hentry","category-microbiologia-clinica","category-murcia","tag-antonio-candido-gomez-garcia","tag-carme-salvador-garcia","tag-jose-angel-garcia-rodriguez","tag-juan-luis-munoz-bellido","tag-manuel-segovia-hernandez","tag-miriam-albert-hernandez"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/114649","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=114649"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/114649\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=114649"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=114649"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=114649"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}