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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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Published in: | Medical mycology (Oxford) 2015-01, Vol.53 (1), p.34-41 |
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creator | Ishida, Kelly de Castro, Rafaela Alves Borba Dos Santos, Luana Pereira Quintella, Leonardo Pereira Lopes-Bezerra, Leila M Rozental, Sonia |
description | 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. |
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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.</description><identifier>ISSN: 1369-3786</identifier><identifier>EISSN: 1460-2709</identifier><identifier>DOI: 10.1093/mmy/myu050</identifier><identifier>PMID: 25306202</identifier><language>eng</language><publisher>England</publisher><subject>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</subject><ispartof>Medical mycology (Oxford), 2015-01, Vol.53 (1), p.34-41</ispartof><rights>The Author 2014. 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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.</description><subject>Amphotericin B - therapeutic use</subject><subject>Animals</subject><subject>Antifungal Agents - therapeutic use</subject><subject>Colony Count, Microbial</subject><subject>Disease Models, Animal</subject><subject>Drug Therapy - methods</subject><subject>Itraconazole - therapeutic use</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Sporothrix</subject><subject>Sporothrix - drug effects</subject><subject>Sporotrichosis - drug therapy</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><issn>1369-3786</issn><issn>1460-2709</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNo9kc9u3CAQh1HUqPnXSx4g4lhVcXcAL2uOyappK62UQ5KzhfGgJcLGBTaN8y5519Bu2hOI-fhGMz9Czhl8ZaDEYhjmxTDvYAkH5JjVEiq-AvWh3IVUlVg18oicpPQIwFaKi4_kiC8FSA78mLxeDdM2ZIzOuJFeX1Ltw4g0RGqD9-E39rSbqctRmzDql-CR5i1GPc2X1CWK1qLJ7glp-V0KtFA5Bk-Dpfg8Fe2AY9ae9i4lHNyoczGmKcSQS8ttSEVSGtz9fdlG90y7qJPzDsdSOiOHVvuEn97PU_Jw8-1-_aPa3H7_ub7aVIY3MlfLRhlhOoYI3PRc9h2yXjfcqI7JlRamtzWvuaoRmFVMoGlAGNFALZWxHRen5PPeO8Xwa4cpt4NLBr3XI4ZdasveQMlGKCjolz1qYkgpom2nMqSOc8ug_RNHW-Jo93EU-OLdu-sG7P-j__Yv3gBrHovj</recordid><startdate>201501</startdate><enddate>201501</enddate><creator>Ishida, Kelly</creator><creator>de Castro, Rafaela Alves</creator><creator>Borba Dos Santos, Luana Pereira</creator><creator>Quintella, Leonardo Pereira</creator><creator>Lopes-Bezerra, Leila M</creator><creator>Rozental, Sonia</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope></search><sort><creationdate>201501</creationdate><title>Amphotericin B, alone or followed by itraconazole therapy, is effective in the control of experimental disseminated sporotrichosis by Sporothrix brasiliensis</title><author>Ishida, Kelly ; de Castro, Rafaela Alves ; Borba Dos Santos, Luana Pereira ; Quintella, Leonardo Pereira ; Lopes-Bezerra, Leila M ; Rozental, Sonia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-589c3cb1ee02cd26dbe1da82c9b167a3cdf424294e01f913ec803c380469cfb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amphotericin B - therapeutic use</topic><topic>Animals</topic><topic>Antifungal Agents - therapeutic use</topic><topic>Colony Count, Microbial</topic><topic>Disease Models, Animal</topic><topic>Drug Therapy - methods</topic><topic>Itraconazole - therapeutic use</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Sporothrix</topic><topic>Sporothrix - drug effects</topic><topic>Sporotrichosis - drug therapy</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishida, Kelly</creatorcontrib><creatorcontrib>de Castro, Rafaela Alves</creatorcontrib><creatorcontrib>Borba Dos Santos, Luana Pereira</creatorcontrib><creatorcontrib>Quintella, Leonardo Pereira</creatorcontrib><creatorcontrib>Lopes-Bezerra, Leila M</creatorcontrib><creatorcontrib>Rozental, Sonia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Medical mycology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishida, Kelly</au><au>de Castro, Rafaela Alves</au><au>Borba Dos Santos, Luana Pereira</au><au>Quintella, Leonardo Pereira</au><au>Lopes-Bezerra, Leila M</au><au>Rozental, Sonia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amphotericin B, alone or followed by itraconazole therapy, is effective in the control of experimental disseminated sporotrichosis by Sporothrix brasiliensis</atitle><jtitle>Medical mycology (Oxford)</jtitle><addtitle>Med Mycol</addtitle><date>2015-01</date><risdate>2015</risdate><volume>53</volume><issue>1</issue><spage>34</spage><epage>41</epage><pages>34-41</pages><issn>1369-3786</issn><eissn>1460-2709</eissn><abstract>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. 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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.</abstract><cop>England</cop><pmid>25306202</pmid><doi>10.1093/mmy/myu050</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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 |
title | Amphotericin B, alone or followed by itraconazole therapy, is effective in the control of experimental disseminated sporotrichosis by Sporothrix brasiliensis |
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