ABSTRACT
We evaluated the in vitro activity of miltefosine against 29 Pythium spp. and the in vivo therapeutic response of 2mg/kg/day of miltefosine given orally to rabbit with pythiosis induced experimentally. The MICs (in µg/mL) of miltefosine was medium-dependent and ranged from 0.5 to 2 and 32-64 on RPMI 1640 and Mueller Hinton broth, respectively. The treatment with miltefosine demonstrated significantly lower subcutaneous lesion areas compared to the control group but was not sufficient for the complete remission of the lesions. This study indicates that miltefosine has limited efficacy against pythiosis and furthers in vitro and in vivo studies are necessary to determine the possible potential of this drug in the treatment of pythiosis.
Subject(s)
Antifungal Agents/therapeutic use , Dermatomycoses/drug therapy , Phosphorylcholine/analogs & derivatives , Pythiosis/drug therapy , Animals , Dermatomycoses/microbiology , Dermatomycoses/pathology , Disease Models, Animal , Disease Progression , Dose-Response Relationship, Drug , Female , Humans , Microbial Sensitivity Tests , Phosphorylcholine/therapeutic use , Pythiosis/microbiology , Pythiosis/pathology , Pythium/isolation & purification , Pythium/pathogenicity , Rabbits , Subcutaneous Tissue/microbiology , Treatment OutcomeABSTRACT
This study evaluated the in vitro and in vivo activity of micafungin alone and in combination with the iron chelator deferasirox against Pythium insidiosum. Micafungin showed a poor in vitro activity when it was used alone, but synergistic interactions were observed for 88.2% of the strains when the drug was combined with deferasirox. Smaller lesions were observed in infected rabbits receiving the combination therapy, although it favored disease dissemination to the lungs. The present results show that micafungin alone is ineffective against P. insidiosum, and the combination micafungin-deferasirox might have deleterious effects for the host.