Diversidade genómica e perfil de resistência dos isolados clínicos de Mycobacterium avium circulantes em Portugal entre 2018 e 2022
Resumo
Introdução: Nos últimos anos, infeções oportunistas por micobactérias não tuberculosas (MNT), têm ganho uma importância crescente na saúde pública, sendo a espécie Mycobacterium avium, a principal responsável pelo aumento de casos de doença humana. Estas infeções manifestam-se principalmente a nível respiratório podendo também ocorrer, sobretudo em indivíduos imunocomprometidos, infeção disseminada. Atualmente, o modo de transmissão não está estabelecido, contudo, a exposição ambiental é considerada a principal fonte de infeção. Assim, é essencial a realização de estudos epidemiológicos para identificar possíveis focos de infeção e, deste modo, melhorar os métodos de vigilância, prevenção e controlo da doença.Objetivo: Avaliação da diversidade genómica e perfil de resistência de isolados clínicos de Mycobacterium avium circulantes em Portugal entre 2018 e 2022.
Métodos: Um conjunto de 42 estirpes de M. avium, isoladas entre 2018 e 2022, no Laboratório Nacional de Referência para Micobactérias (LNR-TB) do INSA, foi caracterizado quanto à sua diversidade genómica através da metodologia de tipagem molecular MIRU-VNTR. Adicionalmente, foram realizados testes de suscetibilidade fenotípica à claritromicina, moxifloxacina e linezolide em 40 (95%) estirpes e de suscetibilidade molecular por pesquisa de mutações nos genes 16S rRNA (rrs) e 23S rRNA (rrl), associados a resistência a aminoglicosídeos (AG) e macrólidos, respetivamente.
Resultados: Os testes de suscetibilidade fenotípica indicaram que 98% (39) das estirpes foram suscetíveis à claritromicina, enquanto apenas 25% (n=10) e 27,5% (n=11) foram suscetíveis ao linezolide e moxifloxacina. Verificou-se uma elevada correlação entre os resultados de testes de suscetibilidade fenotípica e genotípica relativamente aos macrólidos. A genotipagem por MIRU-VNTR revelou uma grande diversidade genética entre as estirpes. Usando threshold de 1 locus e 2 loci de permissão de diferença entre as estirpes, observou-se o agrupamento de dois clusters moleculares e 37 singletons e oito clusters e 20 singletons, respetivamente. No global, a metodologia MIRU-VNTR obteve um índice discriminatório de 0.9988.
Conclusão: Embora tenham sido detetados clusters mo- leculares, a análise dos perfis MIRU-VNTR é insuficiente para estabelecer relações epidemiológicas concretas. Para além dos dados demográficos dos doentes são necessários dados clínicos, o que pode requerer a ponderação de um sistema de notificação obrigatória para uma vigilância laboratorial da doença por M. avium mais assertiva.
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