Comportamento de amostras ambientais e clínicas de Cryptococcus neoformans frente a fungicidas de uso agronômico e ao fluconazol

Abstract

Avaliou-se a atividade de fungicidas azólicos de uso agronômico (epoxiconazol, difenoconazol e ciproconazol) em comparação ao antifúngico de uso terapêutico fluconazol sobre 23 amostras ambientais de Cryptococcus neoformans var neoformans isoladas de fezes de pombos, as quais foram coletadas em fazendas com práticas agrícolas empregando compostos azólicos e 11 amostras clínicas isoladas de pacientes portadores de criptococose. Os testes de sensibilidade foram realizados pela técnica de diluição em agar. A concentração inibitória mínima capaz de inibir 50% dos isolados ambientais (CIM 50) foi de 6,0µg/mL para epoxiconazol, 1,0µg/mL para difenoconazol, 2,0µg/mL para ciproconazol e 64,0µg/mL para fluconazol. Entre os isolados clínicos os valores de CIM 50 foram 2,0µg/mL, 0,38µg/mL, 1,0µg/mL e 16,0µg/mL para epoxiconazol, difenoconazol, ciproconazol e fluconazol, respectivamente. Os valores de CIM 50 em relação aos isolados de origem ambiental foram maiores do que os valores para os isolados de origem clínica. Em nosso estudo, frente ao mesmo antifúngico, as amostras ambientais apresentaram comportamento significativamente diferente em relação às amostras clínicas (p < 0,05). Diferenças (p<0,05) também foram observadas entre os valores de concentração inibitória apresentados pelo fluconazol e os outros antifúngicos de uso agronômico tanto no grupo dos isolados ambientais quanto clínicos.

Crossover between the control of fungal pathogens in medicine and the wider environment, and the threat of antifungal resistance

“…Environmental Cryptococcus spp. such as C. albidus, C. laurentii, C. terrestris, and C. flavescens are about as sensitive to ITZ and VCZ as C. neoformans, but much less sensitive to the agricultural azoles difenoconazole and epoxiconazole, and even to cyproconazole (Drummond et al, 2007;Takahashi et al, 2020), a fungicide known to be especially effective against basidiomycete plant pathogens. Therefore, agricultural azoles are considered as being too weak for Cryptococcus control and resistance selection under agricultural conditions, also because applied field rates and potential residue concentrations in soil are way too low for selecting resistance (Gisi, 2014).…”

“…Basidiomycete yeasts are generally much less, or not at all, sensitive to azoles as well as to 5-FC and (Drummond et al, 2007;Takahashi et al, 2020), a fungicide known to be especially effective against basidiomycete plant pathogens. Therefore, agricultural azoles are considered as being too weak for Cryptococcus control and resistance selection under agricultural conditions, also because applied field rates and potential residue concentrations in soil are way too low for selecting resistance (Gisi, 2014).…”

Is the emergence of fungal resistance to medical triazoles related to their use in the agroecosystems? A mini review

“…These studies suggested that the selection of fungicides with a similar mode of action as those used in human drug therapy for triazole-resistant isolates could contribute to the development of multi-resistant populations. 66 , 67 The development of cross-resistance to triazoles and the low number of triazoles recommended for human therapy relative to the high number of triazoles used in agriculture may affect triazole efficacy for human therapy. 6 , 10 For instance, the fungus Colletotrichum graminicola that causes anthracnose of corn plants is an emerging pathogen in humans.…”

Prevalencia y susceptibilidad de Cryptococcus neoformans aislados del suelo y excretas de palomas en la ciudad de Maceió - Al, Brasil

“…La resistencia de C. neoformans a los antifúngicos azoles fluconazol e itraconazol se ha informado en otros estudios. Drummond et al (2007) evaluaron la susceptibilidad de varias cepas de C. neoformans a esta clase de antifúngicos y evidenciaron que los aislamientos ambientales aumentaron la resistencia a estos medicamentos, suponiendo que la menor susceptibilidad se debe a la posible contaminación ambiental de estos compuestos. En otro estudio, Barbosa Júnior et al (2015) examinaron la susceptibilidad de los aislamientos clínicos de C. neoformans a los agentes antifúngicos para uso hospitalario y observaron una menor sensibilidad al fluconazol e itraconazol, siendo necesaria una concentración de 10 mg/ml (itraconazol) y 12 mg/ml (fluconazol) para promover la inhibición de la mayoría de aislamientos evaluados.…”