Miltefosine-based regimen as salvage therapy in Lomentospora prolificans bone and joint infection

Quaesaet, Luc; Stindel, Éric; Williams, T.; Jaffuel, S.; Moalic, E.; Hermoso, Dea Garcia; Lortholary, Olivier; Ansart, Séverine

doi:10.1016/j.medmal.2017.10.005

Cited by 13 publications

(9 citation statements)

References 10 publications

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“…Miltefosine has also been used successfully in a limited number of cases of the extremely rare highly lethal brain infection by the amoeba Naegleria fowleri and, in the United States, has orphan drug status for the treatment of other amebic infections [62]. Our group and others have previously described the antifungal activity of miltefosine [63][64][65][66][67][68]. Iodoquinol (also referred to as diiodohydroxyquinoline) is an halogenated quinoline derivative (see Supplementary Figure S1) that is used as an intestinal antiparasitic drug, mainly in the treatment of Entamoeba histolytica infections [69], apparently acting by chelation of ferrous ions essential for metabolism.…”

Section: Discussionmentioning

confidence: 99%

Repositionable Compounds with Antifungal Activity against Multidrug Resistant Candida auris Identified in the Medicines for Malaria Venture’s Pathogen Box

Wall

Herrera

Lopez-Ribot

2019

JoF

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Background. Candida auris has spread rapidly around the world as a causative agent of invasive candidiasis in health care facilities and there is an urgent need to find new options for treating this emerging, often multidrug-resistant pathogen. Methods. We screened the Pathogen Box® chemical library for inhibitors of C. auris strain 0390, both under planktonic and biofilm growing conditions. Results. The primary screen identified 12 compounds that inhibited at least 60% of biofilm formation or planktonic growth. After confirmatory dose-response assays, iodoquinol and miltefosine were selected as the two main leading repositionable compounds. Iodoquinol displayed potent in vitro inhibitory activity against planktonic C. auris but showed negligible inhibitory activity against biofilms; whereas miltefosine was able to inhibit the growth of C. auris under both planktonic and biofilm-growing conditions. Subsequent experiments confirmed their activity against nine other strains C. auris clinical isolates, irrespective of their susceptibility profiles against conventional antifungals. We extended our studies further to seven different species of Candida, also with similar findings. Conclusion. Both drugs possess broad spectrum of activity against Candida spp., including multiple strains of the emergent C. auris, and may constitute promising repositionable options for the development of novel therapeutics for the treatment of candidiasis.

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Section: Discussionmentioning

confidence: 99%

Repositionable Compounds with Antifungal Activity against Multidrug Resistant Candida auris Identified in the Medicines for Malaria Venture’s Pathogen Box

Wall

Herrera

Lopez-Ribot

2019

JoF

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“…After a 6-month course of voriconazole, terbinafine, and miltefosine, the symptoms improved, without any evidence of further relapse during a 2-year period of follow-up. 7 Our patient had AML with remission after induction chemotherapy. Before recovery of the neutrophil count, disseminated Lomentospora prolificans infection developed with persistent fungemia despite targeted antifungal therapy with voriconazole + terbinafine.…”

Section: Discussionmentioning

confidence: 67%

Disseminated Lomentospora prolificans Infection in a Patient With Acute Myeloid Leukemia

Wilson

Mackenzie

2022

Infect Dis Clin Pract

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We report a patient with acute myeloid leukemia treated with induction chemotherapy who developed disseminated Lomentospora prolificans infection, with persistent fungemia despite antifungal therapy with voriconazole and terbinafine. Clinical improvement occurred with the addition of miltefosine. The patient survived several months despite further sites of infection developing, but succumbed to relapsed leukemia. There are a handful of reports of the successful use of miltefosine for L. prolificans infection, and this agent seems worthy of further study as an antifungal agent for this organism.

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“…Moreover, nephrotoxicity is rare (Sundar et al, 2002;Chrusciak-Talhari et al, 2011;Dorlo et al, 2012b;Sampaio et al, 2019;Wall et al, 2019). In addition, preliminary studies and case reports presenting promising results have also used miltefosine to treat patients with bone and joint infections caused by L. prolificans, which demonstrate that it could be applied in the clinic with no significant side effects (Kesson et al, 2009;Quaesaet et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

Rollin-Pinheiro

Almeida

Rochetti

et al. 2021

Front. Cell. Infect. Microbiol.

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Scedosporium and Lomentospora species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the in vitro antifungal activity of miltefosine against Scedosporium and Lomentospora species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different Scedosporium and Lomentospora species at 2–4 µg/ml and reduced biofilm formation. The loss of membrane integrity in Scedosporium aurantiacum caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and Scedosporium and Lomentospora cells, highlighting its potential use as new antifungal drug in the future.

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Miltefosine-based regimen as salvage therapy in Lomentospora prolificans bone and joint infection

Cited by 13 publications

References 10 publications

Repositionable Compounds with Antifungal Activity against Multidrug Resistant Candida auris Identified in the Medicines for Malaria Venture’s Pathogen Box

Repositionable Compounds with Antifungal Activity against Multidrug Resistant Candida auris Identified in the Medicines for Malaria Venture’s Pathogen Box

Disseminated Lomentospora prolificans Infection in a Patient With Acute Myeloid Leukemia

Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

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