Thayná Lopes Barreto1, Luana Rossato2, Aline Luiza Duarte de Freitas1, Jacques F Meis3, Luciana Biagini Lopes4, Arnaldo Lopes Colombo2, Kelly Ishida5. 1. Laboratory of Antifungal Chemotherapy, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. 2. Special Laboratory of Mycology, Federal University of São Paulo, São Paulo, Brazil. 3. Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital (CWZ), Nijmegen, The Netherlands; Centre of Expertise in Mycology Radboudumc/CWZ, Nijmegen, The Netherlands. 4. Laboratory of Nanomedicine and Drug Delivery Systems, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. 5. Laboratory of Antifungal Chemotherapy, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: ishidakelly@usp.br.
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 µg/mL and fungicidal activity against planktonic cells of C. auris clinical isolates. MFS antibiofilm activity was observed during biofilm formation (0.25-4 µg/mL) and on pre-formed biofilms (16-32 µg/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.
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 µg/mL and fungicidal activity against planktonic cells of C. auris clinical isolates. MFS antibiofilm activity was observed during biofilm formation (0.25-4 µg/mL) and on pre-formed biofilms (16-32 µg/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.
Authors: Martin Hoenigl; Rosanne Sprute; Amir Arastehfar; John R Perfect; Cornelia Lass-Flörl; Romuald Bellmann; Juergen Prattes; George R Thompson; Nathan P Wiederhold; Mohanad M Al Obaidi; Birgit Willinger; Maiken C Arendrup; Philipp Koehler; Matteo Oliverio; Matthias Egger; Ilan S Schwartz; Oliver A Cornely; Peter G Pappas; Robert Krause Journal: Expert Opin Investig Drugs Date: 2022-06-15 Impact factor: 6.498
Authors: Thaila Fernanda Dos Reis; Maria Augusta Crivelente Horta; Ana Cristina Colabardini; Caroline Mota Fernandes; Lilian Pereira Silva; Rafael Wesley Bastos; Maria Vitória de Lazari Fonseca; Fang Wang; Celso Martins; Márcio L Rodrigues; Cristina Silva Pereira; Maurizio Del Poeta; Koon Ho Wong; Gustavo H Goldman Journal: mBio Date: 2021-08-10 Impact factor: 7.867