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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 56, n. 2 AUG 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/19374-9 - Echinocandins in the control of infections associated to polymicrobial biofilms of Candida spp. and bacteria such as Stapholococcus aureus and Pseudomonas aeruginosa
• Grantee: Kelly Ishida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 18/03708-8 - Antifungal efficacy of miltefosine in alginate nanocarrier in the treatment of aspergillosis
• Grantee: Thayná Lopes Barreto
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/15226-5 - Analysis of the antifungal effect of synthetic compounds on Cryptococcus spp.
• Grantee: Aline Luiza Duarte de Freitas
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/02203-7 - Multidisciplinary and international network to characterize microbiological aspects and natural history of invasive fungal infections due Candida spp
• Grantee: Arnaldo Lopes Colombo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/19095-2 - Investigation of the virulence and immune response against Candida auris using alternative model Caenorhabditis elegans
• Grantee: Luana Rossato
• Support Opportunities: Scholarships in Brazil - Post-Doctoral