• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-03032022-103443
Document
Author
Full name
Lauro Vieira Perdigão Neto
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Levin, Anna Sara Shafferman (President)
Pierrotti, Lígia Camera
Razzolini, Maria Tereza Pepe
Távora, Lara Gurgel Fernandes
Title in Portuguese
Microrganismos gram-negativos multirresistentes: mecanismos de resistência e alternativas terapêuticas
Keywords in Portuguese
Bactérias Gram-Negativas
Carbapenêmicos
Fosfomicina
Genes MDR
Polimixinas
Resistência Microbiana a Medicamentos
Sequenciamento Completo do Genoma
Sinergismo Farmacológico.
Testes de Sensibilidade Microbiana
Abstract in Portuguese
Gram negativos multirresistentes têm se tornado uma ameaça em todo o mundo. Os objetivos desse estudo foram apresentar o relato de caso de uma paciente colonizada por microrganismos distintos carreadores do gene mcr-1, descrever sensibilidade de microrganismos multirresistentes a alternativas terapêuticas e seus mecanismos de resistência e avaliar eficácia e segurança do uso de fosfomicina endovenosa. O estudo descreve o caso de uma paciente internada colonizada concomitantemente com E. coli ST744 e K. pneumoniae ST101, ambos portadores de mcr-1, presente em um plasmídeo de 33.304pb. Além disso, 50 microrganismos multirresistentes (14 A. baumannii, 1 P. aeruginosa, 8 S. marcescens e 27 K. pneumoniae), frequentemente produtores de carbapenemase blaKPC-2 (n=28; 56%), blaOXA-23 (n=11; 22%), e outros mecanismos, como enzimas modificadoras de aminoglicosídeos (n=49; 98%), foram avaliados quanto a opções terapêuticas a carbapenêmicos e polimixinas. Destacaram-se os desempenhos de tigeciclina (96% de sensibilidade); minociclina (100%) e doxiciclina (93%) em A. baumannii, ceftazidima/avibactam (96%) em K. pneumoniae e fosfomicina (88%) em S. marcescens. Por último, descrevemos uma série de 13 pacientes com infecções graves tratadas com fosfomicina. Oito pacientes (62%) foram curados. Sinergismo entre fosfomicina e meropenem foi descrito em nove (82%) isolados. Concluiu-se pela possível transmissão in vivo de mcr-1 em espécies distintas, que tigeciclina, minociclina, doxiciclina, ceftazidima/avibactam e fosfomicina podem ser úteis para tratamento de gram negativos multirresistentes, e que fosfomicina é um antimicrobiano seguro e eficaz, especialmente se combinada com o meropenem.
Title in English
Multiresistant Gram-negative microorganisms: mechanisms of resistance and therapeutic alternatives [
Keywords in English
Carbapenems
Drug Resistance; Microbial
Drug Synergism
Fosfomycin
Genes
Gram-Negative Bacteria
MDR
Microbial Sensitivity Tests
Polymyxins
Whole Genome Sequencing
Abstract in English
Multiresistant gram negatives have become a threat worldwide. The objectives of this study were to present the case report of a patient colonized by distinct microorganisms harboring mcr-1; to describe susceptibility of multiresistant microorganisms to therapeutic alternatives and their mechanisms of resistance; and to evaluate the efficacy and safety of intravenous fosfomycin. The study describes the case of an inpatient colonized concomitantly with E. coli ST744 and K. pneumoniae ST101; both carried mcr-1, present in a 33,304bp plasmid. In addition, 50 multiresistant microorganisms (14 A. baumannii, 1 P. aeruginosa, 8 S. marcescens and 27 K. pneumoniae), that frequently produce carbapenemases blaKPC-2 (n=28; 56%), blaOXA-23 (n= 11; 22%), and other mechanisms such as aminoglycoside modifying enzymes (n=49; 98%), were evaluated for therapeutic alternatives. The performances of tigecycline globally (96% susceptibility); minocycline (100%) and doxycycline (93%) in A. baumannii; as well as ceftazidime/avibactam (96%) in K. pneumoniae, and fosfomycin (88%) in S. marcescens were outstanding. Finally, we described a series of 13 patients with severe infections treated with fosfomycin. Eight patients (62%) were cured. Synergism between fosfomycin and meropenem was described in nine (82%) isolates. We concluded that there is a possible in vivo mcr-1 transmission; that tigecycline, minocycline, doxycycline, ceftazidime/avibactam, and fosfomycin may be helpful for treating gramnegative multiresistant, and that fosfomycin is a safe and effective antimicrobial, especially if combined with meropenem
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2022-03-03
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2024. All rights reserved.