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Epidemiological survey of the pattern of colonization and infection caused by species of the Candida genus in Hospitals of the Lisbon area: emphasis on azole resistance and emergence of non-conventional species
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Até hoje já foram conduzidos em Portugal alguns estudos epidemiológicos focados na caracterização da candidemia invasiva, no entanto, pouco se sabe sobre qual o padrão de colonização das espécies do género Candida em nichos considerados não estéreis onde estas espécies podem existir como comensais. Estudos recentes têm demonstrado o papel importante que as populações comensais podem desenvolver enquanto focos de infeção invasiva. Nesse sentido, neste trabalho foi analisada a frequência de isolamentos de Candida spp. em mais de 1000 isolados recolhidos de amostras estéreis e não estéreis em 5 grandes centros hospitalares e num conjunto de Postos de Recolha da área de Lisboa. Para além da caracterização da frequência dos isolados das espécies nos diferentes produtos, foi analisada a suscetibilidade de um conjunto alargado destes isolados a 3 antifúngicos com relevância na prática clínica, anfotericina B, fluconazol e voriconazol. No geral, os resultados obtidos confirmam a elevada prevalência de C. albicans enquanto espécie colonizadora de amostras estéreis e não estéreis. Apesar disso, uma percentagem significativa de isolados (26 %) pertencentes a espécies Candida não-albicans foi observada, com ênfase para as espécies C. glabrata (14 %), C. parapsilosis (5 %) e C. tropicalis (4 %). Esta distribuição é consistente com os resultados reportados em estudos epidemiológicos desenvolvidos anteriormente em Portugal e ao redor do mundo. A prevalência de resistência aos antifúngicos observada foi baixa em todas as espécies (0,36 %) tendo sido possível identificar pelo menos 1 isolado de C. glabrata, recolhido de exsudado vaginal, resistente a fluconazol e voriconazol. Tentou-se verificar se este fenótipo de resistência estaria subjacente à existência de mutações de ganho de função na sequência do regulador transcricional CgPdr1 tendo-se identificado 3 mutações, nomeadamente, V91I, L98S e D243N.
To date, some epidemiological studies focused on cases of invasive candidemia have been conducted in Portugal, however, little is known about what the pattern of colonization of species of the genus Candida in niches considered non-sterile where this species can exist as commensals. Recent studies have shown the important role that commensal population can develop as foci of invasive infections. In this sense, in this work it was examined the frequency of isolation of Candida spp. in more than 1000 isolates collected from sterile and non-sterile samples in 5 major hospital centers and in a set of Collection stations of the Lisbon area. Besides the characterization of the frequency of species isolates in the different products, it was also tested the susceptibility to 3 antifungals with relevance in the clinical practice, amphotericin B, fluconazol and voriconazol. In general, the results obtained confirmed the high prevalence of C. albicans while colonizer species in sterile and non-sterile samples. Nevertheless, a significant percentage of isolates (26 %) belonging to non-Candida albicans Candida species was also observed with emphasis on C. glabrata (14 %), C. parapsilosis (5 %) and C. tropicalis (4 %). This distribution is consistent with the results reported in other epidemiological surveys undertaken in Portugal and worldwide. The incidence of resistance to antifungals observed was low in every species (0,36 %) and it was possible to identify at least 1 C. glabrata isolate, from a vaginal niche, resistant to fluconazol and voriconazol. It was attempted to verify if this phenotype of resistance would be underlying the existence of gain of functions mutations in the transcriptional regulator CgPDR1 sequence and 3 mutations were identified, namely, V91I, L98S e D243N.
To date, some epidemiological studies focused on cases of invasive candidemia have been conducted in Portugal, however, little is known about what the pattern of colonization of species of the genus Candida in niches considered non-sterile where this species can exist as commensals. Recent studies have shown the important role that commensal population can develop as foci of invasive infections. In this sense, in this work it was examined the frequency of isolation of Candida spp. in more than 1000 isolates collected from sterile and non-sterile samples in 5 major hospital centers and in a set of Collection stations of the Lisbon area. Besides the characterization of the frequency of species isolates in the different products, it was also tested the susceptibility to 3 antifungals with relevance in the clinical practice, amphotericin B, fluconazol and voriconazol. In general, the results obtained confirmed the high prevalence of C. albicans while colonizer species in sterile and non-sterile samples. Nevertheless, a significant percentage of isolates (26 %) belonging to non-Candida albicans Candida species was also observed with emphasis on C. glabrata (14 %), C. parapsilosis (5 %) and C. tropicalis (4 %). This distribution is consistent with the results reported in other epidemiological surveys undertaken in Portugal and worldwide. The incidence of resistance to antifungals observed was low in every species (0,36 %) and it was possible to identify at least 1 C. glabrata isolate, from a vaginal niche, resistant to fluconazol and voriconazol. It was attempted to verify if this phenotype of resistance would be underlying the existence of gain of functions mutations in the transcriptional regulator CgPDR1 sequence and 3 mutations were identified, namely, V91I, L98S e D243N.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Candidose, Candidemia, Colonização por Candida, Candida albicans, Espécies de Candida não-albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Resistência aos antifúngicos, Candida africana Mestrado Integrado - 2019