Miltefosine as an alternative strategy in the treatment of the emerging fungus Candida auris

Autor(es)

Barreto, Thayna Lopes ^[1] ; Rossato, Luana ^[2] ; Duarte de Freitas, Aline Luiza ^[1] ; Meis, Jacques F. ^{[3, 4]} ; Lopes, Luciana Biagini ^[5] ; Colombo, Arnaldo Lopes ^[2] ; Ishida, Kelly ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Antifungal Chemotherapy, Dept Microbiol, Inst Biomed Sci, Prof Lineu Prestes Ave 1374, ICB 2, Lab 150, BR-05508000 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Special Lab Mycol, Sao Paulo - Brazil

^[3] Canisius Wilhelmina Hosp CWZ, Dept Med Microbiol & Infect Dis, Nijmegen - Netherlands

^[4] Radboudumc CWZ, Ctr Expertise Mycol, Nijmegen - Netherlands

^[5] Univ Sao Paulo, Lab Nanomed & Drug Delivery Syst, Dept Pharmacol, Inst Biomed Sci, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 56, n. 2 AUG 2020.
• Citações Web of Science: 0

Resumo

Objectives: Candida auris (C. auris) is an emerging fungal species that is able to develop multidrug resistance and outbreaks of invasive infections worldwide with high mortality rates. To increase the treatment options for C. auris infection this study assessed the efficacy of miltefosine (MFS), that has demonstrated a broad-spectrum antifungal action in vitro. This study aimed to: (i) evaluate the in vitro antifungal activity of MFS against C. auris clinical isolates in the planktonic and biofilm lifestyles; and (ii) compare the activity of MFS in its free form and encapsulated in alginate nanoparticles (MFS-AN) in Galleria mellonella larvae infected by C. auris. Methods: The antifungal susceptibility test was performed using broth microdilution method and the in vivo treatment in Galleria mellonella larval infection model. Results: MFS exhibited in vitro inhibitory effects at MICs ranging 1-4 mu g/mL and fungicidal activity against planktonic cells of C. auris clinical isolates. MFS antibiofilm activity was observed during biofilm formation (0.25-4 mu g/mL) and on pre-formed biofilms (16-32 mu g/mL). Moreover, the dispersed cells from C. auris biofilms had a similar susceptibility to those obtained for planktonic cells. Treatment with free MFS or MFS-AN resulted in significant improvements in the survival and morbidity rates of Galleria mellonella larvae infected by C. auris. In addition, reduction of fungal burden (0.5-1 log CFU/g) and granuloma formation were observed when compared with the untreated group. Conclusions: The findings suggest that both the free MFS and MFS-AN have potential for the treatment of fungal infections caused by the emerging C. auris. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. (AU)

• Processo FAPESP: 17/19374-9 - Equinocandinas no controle de infecções associadas a biofilmes polimicrobianos de Candida spp. e bactérias como Stapholococcus aureus e Pseudomonas aeruginosa
• Beneficiário: Kelly Ishida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/13877-1 - Nanocarreadores para a quimioprevenção e tratamento localizado de tumores de mama
• Beneficiário: Luciana Biagini Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 18/03708-8 - Eficácia antifúngica da miltefosina em nanocarreador de alginato no tratamento da aspergilose
• Beneficiário: Thayná Lopes Barreto
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/15226-5 - Análise do efeito antifúngico de compostos sintéticos sobre Cryptococcus spp.
• Beneficiário: Aline Luiza Duarte de Freitas
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/02203-7 - Rede multidisciplinar internacional para caracterização de aspectos microbiológicos e da história natural de Infecções Fúngicas Invasivas (IFI) por espécies do gênero Candida
• Beneficiário: Arnaldo Lopes Colombo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/19095-2 - Avaliação da virulência e resposta imune frente à Candida auris utilizando o modelo alternativo Caenorhabditis elegans
• Beneficiário: Luana Rossato
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado