In vitro inhibitory effect of miltefosine against strains of Histoplasma capsulatum var. capsulatum and Sporothrix spp.

Abstract

Miltefosine (MIL), originally developed for use in cancer chemotherapy, has been shown to have important antifungal activity against several pathogenic fungi. Our aim in this study was to determine the in vitro activity of MIL against the dimorphic fungi Histoplasma capsulatum and Sporothrix spp. This was done using the broth microdilution method. MIL had an in vitro inhibitory effect against all strains of H. capsulatum var. capsulatum and Sporothrix spp. analyzed. The minimal inhibitory concentrations (MIC) varied from 0.25 μg/ml to 2 μg/ml for H. capsulatum var. capsulatum in the filamentous phase and from 0.125 μg/ml to 1 μg/ml in the yeast phase. The MIC interval for Sporothrix spp. in the filamentous phase was 0.25-2 μg/ml. The minimal fungicidal concentrations (MFCs) were ≤4 μg/ml for isolates of both analyzed species. This study demonstrates that MIL has an antifungal effect in vitro against two potentially pathogenic fungi and that more studies should be performed in order to evaluate its applicability in vivo.

Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

“…Additionally, PCZ also showed low MICs against 2 out of 3 clinical isolates of the rare species S. mexicana , including CBS 132928 (MIC = 1 μg/mL) and CBS 132927 (MIC = 2 μg/mL). Only a few strains of S. mexicana have been described in the literature [1,10], and the species has been reported as tolerant to most commercially available drugs [14,33]. …”

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis

“…Recently, some reports have attributed the development of resistance to miltefosine during the treatment of visceral leishmaniasis to the overexpression of an ABC transporter (Leishmania tropica MDR1 [LtrMDR1]) and to changes in membrane sterol composition (25,26). The broad-spectrum antifungal activity of miltefosine has been demonstrated in vitro against planktonic cells of several medically important fungi, including dermatophytes, Candida sp., Cryptococcus sp., Aspergillus sp., Fusarium sp., Scedosporium sp., Histoplasma capsulatum, Rhizopus sp., and Sporothrix schenckii (27)(28)(29)(30)(31)(32), and no reports about resistance development have been made so far.…”

<i>Paracoccidioides lutzii</i> e outros fungos de importância médica: desenvolvimento de vacina terapêutica e tratamento alternativo com compostos sintéticos no controle das micoses sistêmicas.

“…Para quantificar a produção de melanina produzida pelas leveduras após a MLT é um fármaco de fosfolípido de alquilo, um análogo de fosfocolina, que dispõe tem um amplo espectro de atividade contra parasitas (123,124), leveduras, fungos filamentosos e leveduras dimórficas. (128)(129)(130)134). No presente estudo foi explorado pela primeira vez a atividade da MLT contra espécies de Paracoccidioides.…”

“…Sporothrix spp., H. capsulatum, and C. immitis,(128)(129)(130)135), no presente estudo foi visto que a MLT também foi fungicida para Paracoccidioides spp. Paracoccidioides spp.…”

“…assim como também foi observado em leveduras de C. albicans tratadas ou não com inibidores da biossíntese de ergosterol (147,148) e S. brasiliensis(130,135). Recentemente, foi visto que a MLT reduz ergosterol da membrana de C. posadasii e H. capsulatum(128) e também altera a permeabilidade da membrana citoplasmática de C. posadasii, H. capsulatum, e S. brasiliensis, na qual resulta no rompimento da membrana (128)(129)(130)…”