Caracterização molecular de Escherichia coli e Klebsiella pneumoniae produtoras de β-lactamases de amplo espectro de origem clínica humana
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2012
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A introdução de agentes antimicrobianos na prática clínica é, normalmente,
seguida de um rápido aparecimento de estirpes bacterianas resistentes a esses mesmos
agentes. Este facto leva ao esgotamento de antibióticos eficazes no tratamento de
infecções bacterianas, sendo sugerido que o século XXI se poderá assemelhar à era préantimicrobiana.
Apesar do estudo da resistência a antibióticos incidir, maioritariamente,
sobre microrganismos patogénicos, deve ter-se também em conta que o problema da
resistência se aplica, também, a bactérias não patogénicas. Estas são capazes de adquirir
e, posteriormente, transmitir genes de resistência a outras bactérias potencialmente
patogénicas e de interesse clínico. No tratamento de infecções bacterianas, antibióticos
β-lactâmicos apresentam-se como uma das classes terapêuticas mais importantes, sendo
as mais usadas em medicina humana e veterinária. Contudo, vários estudos indicam que
a resistência a estes antibióticos está a aumentar. Escherichia coli e Klebsiella
pneumoniae multi-resistentes produtoras de β-lactamases de amplo espectro (BLAE)
ocupam o topo da lista dos seis patogénicos mais preocupantes para a saúde humana.
Neste trabalho realizou-se o estudo da sensibilidade a agentes antimicrobianos
de isolados clínicos de E. coli e K. pneumoniae, obtidos de amostras de urina de
pacientes do Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE (CHTMAD),
verificando-se elevadas percentagens de resistência a 16 antibióticos de uso clínico
comum, bem como uma elevada prevalência de multi-resistência. Efectuou-se um
estudo genotípico dos isolados, observando-se uma relação positiva entre determinados
genes e fenótipo resistente, bem como a influência de mutações nucleotídicas e
consequentes alterações aminoacídicas na aquisição de resistência. Verificou-se a
associação dos isolados de E. coli a grupos filogenéticos correspondentes a estirpes
virulentas extra-intestinais.
Com a realização deste trabalho, foi possível obter uma visão sobre o panorama
das resistências antimicrobianas em pacientes do CHTMAD, perspectivando-se a
necessidade de contínuos estudos para o conhecimento dos padrões de resistência e
presença de genes associados não só em recintos hospitalares, mas a nível global.
The introduction of antimicrobial agents in clinical practice is usually followed by a fast emergence of bacteria resistant to those drugs. This leads to a depletion of effective antibiotics, being suggested that the 21st century may resemble the preantimicrobial era. Despite the study of drug resistance being focused mainly on pathogens, we must also have in mind that the resistance problem also applies to nonpathogenic bacteria. These are capable of acquiring and transmitting resistance genes to other potentially pathogenic and of clinical interest bacteria. In treating bacterial infections, β-lactams are one of the major therapeutic classes, being the most used in human and veterinary medicine. Nevertheless, several studies indicate that resistance to this kind of antibiotics is rising. Multi-resistant extended-spectrum β-lactamase (ESBL) -producing Escherichia coli and Klebsiella pneumoniae are on the top of the list of the six most worrying pathogens for human health. This work intended to study the susceptibility of clinical isolates of E. coli and K. pneumoniae, obtained from urine samples of patients from the Hospital Center of Trás-os-Montes and Alto Douro, EPE (CHTMAD). High percentages of resistance to 16 common-clinically-used antibiotics were observed, as well as a high prevalence of multi-resistant isolates. A genotypic study was performed and a positive relationship between certain genes and resistant phenotype was detected, the influence of nucleotidic mutations and the consequent aminoacid changes on the acquisition of resistance was also identified. The association of the E. coli isolates to phylogenetic groups corresponding to virulent extra-intestinal strains has been shown. With this work, a vision on the antimicrobial resistance in patients of CHTMAD was obtained, being showed the need of continuous studies to obtain knowledge on resistance patterns and presence of associated genes not only on hospital facilities, but also in a global level.
The introduction of antimicrobial agents in clinical practice is usually followed by a fast emergence of bacteria resistant to those drugs. This leads to a depletion of effective antibiotics, being suggested that the 21st century may resemble the preantimicrobial era. Despite the study of drug resistance being focused mainly on pathogens, we must also have in mind that the resistance problem also applies to nonpathogenic bacteria. These are capable of acquiring and transmitting resistance genes to other potentially pathogenic and of clinical interest bacteria. In treating bacterial infections, β-lactams are one of the major therapeutic classes, being the most used in human and veterinary medicine. Nevertheless, several studies indicate that resistance to this kind of antibiotics is rising. Multi-resistant extended-spectrum β-lactamase (ESBL) -producing Escherichia coli and Klebsiella pneumoniae are on the top of the list of the six most worrying pathogens for human health. This work intended to study the susceptibility of clinical isolates of E. coli and K. pneumoniae, obtained from urine samples of patients from the Hospital Center of Trás-os-Montes and Alto Douro, EPE (CHTMAD). High percentages of resistance to 16 common-clinically-used antibiotics were observed, as well as a high prevalence of multi-resistant isolates. A genotypic study was performed and a positive relationship between certain genes and resistant phenotype was detected, the influence of nucleotidic mutations and the consequent aminoacid changes on the acquisition of resistance was also identified. The association of the E. coli isolates to phylogenetic groups corresponding to virulent extra-intestinal strains has been shown. With this work, a vision on the antimicrobial resistance in patients of CHTMAD was obtained, being showed the need of continuous studies to obtain knowledge on resistance patterns and presence of associated genes not only on hospital facilities, but also in a global level.
Descrição
Dissertação de Mestrado em Genética Molecular Comparativa e Tecnológica
Palavras-chave
Escherichia coli , Klebsiella pneumoniae , Resistência microbiana a medicamentos , Genes de resistência