A carregar...
Publicação
Caracterização do micobioma em unidades de cuidados intensivos
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 28.2 MB | Adobe PDF |
Orientador(es)
Resumo(s)
O micobioma é um componente importante do microbioma humano. Apesar da sua relevância tem sido pouco estudado, especialmente em doentes internados em unidades de cuidados intensivos (UCI). Neste contexto, este estudo prospetivo multicêntrico, realizado entre 2020 e 2022 em doentes em UCI na área metropolitana de Lisboa teve como objetivo avaliar a importância do ambiente nosocomial na colonização fúngica da pele, com especial enfoque no género Candida e particularmente C. auris. Mais especificamente, avaliar a dinâmica da colonização fúngica e os factores de risco associados tanto na admissão (D1) quanto ao longo do internamento, ao 5º (D5) e 8º dia (D8). A análise incluiu a caracterização do micobioma, os perfis de susceptibilidade aos principais antifúngicos utilizados na prática clínica e o impacto nos índices de sobrevivência.
De 675 doentes foram obtidos 988 exsudados combinados bilaterais das regiões intertriginosas axilar e inguinal, especificamente: 675, 203 e 110 amostras em D1, D5 e D8 respetivamente. A micobiota (n=371) foi identificada por métodos fenotípicos, MALDI-TOF MS e PCR, e verificou-se que o género Candida foi dominante (n=355). C. albicans foi a espécie mais prevalente (52,1%) seguida por C. parapsilosis (30,7%). Porém, identificou-se um desvio nesta coorte, de C. albicans para espécies de Candida não-albicans, dependente da unidade hospitalar (p= 0,011). Os resultados evidenciaram a ausência de C. auris apesar da sua pesquisa por PCR em tempo real e métodos convencionais, aos quais se adicionou um meio de cultura seletivo, desenvolvido neste estudo, o Manitol Salt Agar Auris.
A colonização fúngica observada foi de 184/675 (27,3%), 87/203 (42,8%) e 58/110 (52,7%) no D1, D5 e D8, respetivamente. A dinâmica da colonização por Candida spp. foi significativamente associada ao tipo de UCI (Odds Ratio (OR)= 2,03, IC 95% 1,22- 3,39, p= 0,007), infeção respiratória (OR= 1,74, IC 95% 1. 17-2,58, p= 0,006),
hemodiálise (OR = 2,19, IC 95% 1,17-4,10, p= 0,014), COVID-19 (OR = 0,37, IC 95%
0,14-0,99, p= 0,048) e a uma menor taxa de sobrevivência a 3 meses (p= 0,008). O grau de colonização por Candida spp. foi elevado (superior a 100 UFC/mL) em 77,2% dos doentes.
O micobioma das amostras dos doentes em UCI (D1 e D8) obtido por metasequenciação evidenciou diversidade genética, com predomínio marcado do género Candida, mas sem associação significativa com o internamento na UCI (p= 0,499).
Os perfis de susceptibilidade antifúngica in vitro para o fluconazol, voriconazol, anfotericina B e anidulafungina, foram obtidos através do método epsilométrico (Etest®) e mostraram que a resistência continua a ser pouco comum entre os isolados de Candida spp. nas UCI investigadas, sem alterações significativas ao longo do tempo de internamento ou entre unidades hospitalares.
Destaca-se deste estudo, a utilização da colonização da pele por Candida spp. como uma ferramenta de alerta precoce para informar sobre os factores de risco e índices de sobrevivência dos doentes em estado crítico. Perspetiva-se que o conhecimento da dinâmica do micobioma da pele em doentes internados em UCI seja fundamental para compreender as alterações associadas à colonização, bem como a possível infeção dos doentes.
The mycobiome is an important component of the human microbiome. Despite its significance, it has been under-researched, particularly in patients hospitalized in intensive care units (ICU). In this context, this multicentre prospective study, carried out between 2020 and 2022 in patients admitted to ICUs in the Lisbon metropolitan area, aimed to assess the importance of the nosocomial environment in fungal colonisation of the skin, with a special focus on the Candida genus and particularly C. auris. Specifically, to assess the dynamics of fungal colonisation and its risk factors on admission (D1) and for the length of ICU stay, at day 5 (D5) and 8 (D8). The analysis included the characterization of the mycobiome, susceptibility profiles to the main antifungals drugs used in clinical practice, and the impact on survival rates. From 675 patients, 988 bilateral combined axillary/inguinal swabs were collected, particularly, 675, 203 and 110 samples on D1, D5 and D8 respectively. The mycobiota (n=371) was identified by phenotypic methods, MALDI-TOF MS and PCR and it was found that Candida spp. was dominant (n=355). C. albicans was the most prevalent species (52.1%) followed by C. parapsilosis. However, a shift was identified in this cohort from C. albicans to non-albicans Candida species, depending on the hospital unit (p= 0.011). The results showed the absence of C. auris despite its detection by real time PCR and culture-based methods, to which a selective culture medium developed in this study, Mannitol Salt Agar Auris, was added. The fungal colonisation observed was 184/675 (27.3%), 87/203 (42.8%) and 58/110 (52.7%) on D1, D5 and D8, respectively. The dynamics of colonisation by Candida spp. was significantly associated with the type of ICU (odds ratio (OR) = 2.03, 95% CI 1.22- 3.39, p= 0.007), respiratory infection (OR = 1.74, 95% CI 1. 17-2.58, p= 0.006), haemodialysis (OR = 2.19, 95% CI 1.17-4.10, p= 0.014), COVID-19 (OR = 0.37, 95% CI 0.14-0.99, p= 0.048) and a lower survival rate at 3 months (p= 0.008). The degree of colonisation by Candida spp. was high (> 100 CFU/mL) in 77.2% of patients. The mycobiome obtained by metasequencing patients in the ICU (D1 and D8) showed genetic diversity, with a marked predominance of the Candida spp., but no significant association with all length of ICU stay (p= 0.499). In vitro antifungal susceptibility profiles for fluconazole, voriconazole, amphotericin B and anidulafungin were obtained using the epsilometric method (Etest®) and showed that resistance continues to be uncommon among Candida spp. isolates in the ICUs investigated, with no significant changes over the length of stay or between hospital units. This study highlights the clinical investigation of skin colonisation by Candida spp. as an early warning tool to provide information on risk factors and survival rates in critically ill patients. Clarifying the dynamics of the skin mycobiome in ICU patients is anticipated to be fundamental in understanding the changes associated with colonization and the potential for patient infection.
The mycobiome is an important component of the human microbiome. Despite its significance, it has been under-researched, particularly in patients hospitalized in intensive care units (ICU). In this context, this multicentre prospective study, carried out between 2020 and 2022 in patients admitted to ICUs in the Lisbon metropolitan area, aimed to assess the importance of the nosocomial environment in fungal colonisation of the skin, with a special focus on the Candida genus and particularly C. auris. Specifically, to assess the dynamics of fungal colonisation and its risk factors on admission (D1) and for the length of ICU stay, at day 5 (D5) and 8 (D8). The analysis included the characterization of the mycobiome, susceptibility profiles to the main antifungals drugs used in clinical practice, and the impact on survival rates. From 675 patients, 988 bilateral combined axillary/inguinal swabs were collected, particularly, 675, 203 and 110 samples on D1, D5 and D8 respectively. The mycobiota (n=371) was identified by phenotypic methods, MALDI-TOF MS and PCR and it was found that Candida spp. was dominant (n=355). C. albicans was the most prevalent species (52.1%) followed by C. parapsilosis. However, a shift was identified in this cohort from C. albicans to non-albicans Candida species, depending on the hospital unit (p= 0.011). The results showed the absence of C. auris despite its detection by real time PCR and culture-based methods, to which a selective culture medium developed in this study, Mannitol Salt Agar Auris, was added. The fungal colonisation observed was 184/675 (27.3%), 87/203 (42.8%) and 58/110 (52.7%) on D1, D5 and D8, respectively. The dynamics of colonisation by Candida spp. was significantly associated with the type of ICU (odds ratio (OR) = 2.03, 95% CI 1.22- 3.39, p= 0.007), respiratory infection (OR = 1.74, 95% CI 1. 17-2.58, p= 0.006), haemodialysis (OR = 2.19, 95% CI 1.17-4.10, p= 0.014), COVID-19 (OR = 0.37, 95% CI 0.14-0.99, p= 0.048) and a lower survival rate at 3 months (p= 0.008). The degree of colonisation by Candida spp. was high (> 100 CFU/mL) in 77.2% of patients. The mycobiome obtained by metasequencing patients in the ICU (D1 and D8) showed genetic diversity, with a marked predominance of the Candida spp., but no significant association with all length of ICU stay (p= 0.499). In vitro antifungal susceptibility profiles for fluconazole, voriconazole, amphotericin B and anidulafungin were obtained using the epsilometric method (Etest®) and showed that resistance continues to be uncommon among Candida spp. isolates in the ICUs investigated, with no significant changes over the length of stay or between hospital units. This study highlights the clinical investigation of skin colonisation by Candida spp. as an early warning tool to provide information on risk factors and survival rates in critically ill patients. Clarifying the dynamics of the skin mycobiome in ICU patients is anticipated to be fundamental in understanding the changes associated with colonization and the potential for patient infection.
Descrição
Palavras-chave
Ciências biomédicas Microbiologia Micobioma Cuidados intensivos Candida spp Candida auris