Amphotericin B, alone or followed by itraconazole therapy, is effective in the control of experimental disseminated sporotrichosis by Sporothrix brasiliensis

Sporothrix brasiliensis is a highly virulent member of the S. schenckii complex, which is responsible for the emergence of the epidemic sporotrichosis in southeastern Brazil over the last two decades. There are no in vivo studies on the sensitivity of S. brasiliensis to the therapeutic regimens used...

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Bibliographic Details
Published in:Medical mycology (Oxford) 2015-01, Vol.53 (1), p.34-41
Main Authors: Ishida, Kelly, de Castro, Rafaela Alves, Borba Dos Santos, Luana Pereira, Quintella, Leonardo Pereira, Lopes-Bezerra, Leila M, Rozental, Sonia
Format: Article
Language:English
Subjects:
Amphotericin B - therapeutic use
Animals
Antifungal Agents - therapeutic use
Colony Count, Microbial
Disease Models, Animal
Drug Therapy - methods
Itraconazole - therapeutic use
Male
Mice, Inbred BALB C
Sporothrix
Sporothrix - drug effects
Sporotrichosis - drug therapy
Survival Analysis
Treatment Outcome
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Summary:Sporothrix brasiliensis is a highly virulent member of the S. schenckii complex, which is responsible for the emergence of the epidemic sporotrichosis in southeastern Brazil over the last two decades. There are no in vivo studies on the sensitivity of S. brasiliensis to the therapeutic regimens used to treat sporotrichosis. Here, we evaluated the efficacy and safety of antifungal treatments against S. brasiliensis using a murine model of disseminated sporotrichosis. In vitro, S. brasiliensis yeasts were sensitive to low concentrations of amphotericin B-deoxycholate (AMB-d) and itraconazole (ITZ), the latter having greater selectivity toward the fungus. The following treatment regimens were tested in vivo: intravenous AMB-d for 7 days post-infection (p.i.), oral ITZ for up to 30 days p.i., and AMB-d followed by ITZ (AMB-d/ITZ). AMB-d and AMB-d/ITZ led to 100% survival of infected mice at the end of the 45-day experimental period. Although all treatments extended mice survival, only AMB-d and AMB-d/ITZ significantly reduced fungal load in all organs, but AMB-d/ITZ led to a more consistent decrease in overall fungal burden. No treatment increased the levels of serum toxicity biomarkers. Taken together, our results indicate that AMB-d/ITZ is the best therapeutic option for controlling disseminated sporotrichosis caused by S. brasiliensis.
ISSN:1369-3786
1460-2709
DOI:10.1093/mmy/myu050