Publication: Caracterización de levaduras causantes de fungemia: identificación y sensibilidad antifúngica, epidemiología molecular y factores de patogenicidad
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2018-02-15
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Universidad Complutense de Madrid
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Abstract
El estudio de la infección profunda causada por levaduras, en especial la fungemia, ha sido abordado históricamente bajo el análisis de los pacientes que la sufrían. Determinar los factores predisponentes de la infección, estudiar el tratamiento antifúngico más efectivo, y analizar el pronóstico de los pacientes ha sido la motivación principal del estudio en esta área de las infecciones fúngicas. Sin embargo, el estudio integral del patógeno desde diferentes puntos de vista microbiológicos, sin tener en cuenta al paciente afectado, ha recibido menos atención. Parece razonable pues que, además del paciente infectado y su manejo médico, las características propias del patógeno tengan una contribución y protagonismo especial. Esta tesis ha pretendido estudiar las cepas causantes de fungemia en pacientes ingresados en un gran hospital de Madrid desde diferentes puntos de vista microbiológicos, algunos de ellos poco representados en la literatura médica, estructurándose en los siguientes cuatro bloques: (1) Identificación y sensibilidad a antifúngicos de levaduras causantes de fungemia, (2) Caracterización genotípica y estudio de la diversidad clonal de las principales especies de Candida causantes de candidemia, (3) Estudio de la formación de biopelículas de aislados de Candida spp. causantes de fungemia y determinación de su susceptibilidad antifúngica, y (4) Estudio de la patogenicidad de Candida spp. en base a la letalidad sobre un modelo de G. mellonella El estudio preciso de la epidemiología de las especies causantes de fungemia es clínicamente relevante ya que permite elegir de la manera más precisa posible la terapia antifúngica empírica cuando aún no se cuenta con la identificación a nivel de especie. Esto se debe a que la especie se relaciona, con frecuencia, con un perfil de sensibilidad característico. Además, la distribución de especies causantes de fungemia muestra diferencias geográficas marcadas...
The study of deep-seated infections caused by yeasts, especially fungemia, has been historically done by studying the host risk factors. The determination of the predisposing factors of the infection, the study of the most effective antifungal treatment, and the analysis of the prognosis of patients has been the main motivation of research in this area. However, the study of the pathogen from different microbiological points of view, without considering the host factors, has received less attention. It seems logical then that, together with the study of the infected patients and their medical management, the characteristics of the pathogen receive also the attention. In this thesis strains causing fungemia in patients admitted to a large hospital in Madrid have been studied from different microbiological points of view, some of them poorly represented in the medical literature. The project has been structured in the following four chapters: (1) Molecular identification and antifungal susceptibility testing (2) Genotypic characterization and study of the clonal diversity of the main Candida species causing candidemia, (3) Study of the biofilm formation of Candida spp. isolates causing fungemia and study of the biofilms antifungal susceptibility, and (4) Study of the virulence of Candida spp. on a G. mellonella model. The precise study of the epidemiology of the species causing fungemia is clinically relevant since it allows establishing empirical antifungal therapy as accurate as possible when there is no identification at the species level yet, because of the well-known species and antifungal susceptibility profile...
The study of deep-seated infections caused by yeasts, especially fungemia, has been historically done by studying the host risk factors. The determination of the predisposing factors of the infection, the study of the most effective antifungal treatment, and the analysis of the prognosis of patients has been the main motivation of research in this area. However, the study of the pathogen from different microbiological points of view, without considering the host factors, has received less attention. It seems logical then that, together with the study of the infected patients and their medical management, the characteristics of the pathogen receive also the attention. In this thesis strains causing fungemia in patients admitted to a large hospital in Madrid have been studied from different microbiological points of view, some of them poorly represented in the medical literature. The project has been structured in the following four chapters: (1) Molecular identification and antifungal susceptibility testing (2) Genotypic characterization and study of the clonal diversity of the main Candida species causing candidemia, (3) Study of the biofilm formation of Candida spp. isolates causing fungemia and study of the biofilms antifungal susceptibility, and (4) Study of the virulence of Candida spp. on a G. mellonella model. The precise study of the epidemiology of the species causing fungemia is clinically relevant since it allows establishing empirical antifungal therapy as accurate as possible when there is no identification at the species level yet, because of the well-known species and antifungal susceptibility profile...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Microbiología II, leída el 27-06-2017