Limited Activity Of Miltefosine In Murine Models Of Cryptococcal Meningoencephalitis And Disseminated Cryptococcosis

Simple item page
dc.contributor.utaustinauthorWiederhold, Nathan P.en
dc.creatorWiederhold, Nathan P.en
dc.creatorNajvar, Laura K.en
dc.creatorBocanegra, Rosieen
dc.creatorKirkpatrick, William R.en
dc.creatorSorrell, Tania C.en
dc.creatorPatterson, Thomas F.en
dc.date.accessioned2015-09-09T15:50:38Zen
dc.date.available2015-09-09T15:50:38Zen
dc.date.issued2013-02en
dc.description.abstractMiltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.en
dc.description.departmentPharmaceutical Sciencesen
dc.description.sponsorshipen
dc.identifier.citationNathan P. Wiederhold, Laura K. Najvar, Rosie Bocanegra, William R. Kirkpatrick, Tania C. Sorrell, Thomas F. Patterson. Limited Activity Of Miltefosine In Murine Models Of Cryptococcal Meningoencephalitis And Disseminated Cryptococcosis. Antimicrobial Agents and Chemotherapy, (Feb. 2013) pp.745-750. DOI:10.1128/AAC.01624-12en
dc.identifier.doi10.1128/aac.01624-12en
dc.identifier.issn0066-4804en
dc.identifier.urihttp://hdl.handle.net/2152/31112en
dc.identifier.urlen
dc.language.isoEnglishen
dc.relation.ispartofserialAntimicrobial Agents and Chemotherapyen
dc.rightsAdministrative deposit of works to Texas ScholarWorks: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access or the publisher allows a PDF version of the article to be freely posted online. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.rights.holderen
dc.subjectindian visceral leishmaniasisen
dc.subjectworld cutaneous leishmaniasisen
dc.subjectamphotericin-ben
dc.subjectfungicidal activityen
dc.subjectoral miltefosineen
dc.subjectin-vitroen
dc.subjectmeningitisen
dc.subjectfluconazoleen
dc.subjecthexadecylphosphocholineen
dc.subjectflucytosineen
dc.subjectmicrobiologyen
dc.subjectpharmacology & pharmacyen
dc.titleLimited Activity Of Miltefosine In Murine Models Of Cryptococcal Meningoencephalitis And Disseminated Cryptococcosisen
dc.typeArticleen

Access full-text files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
LimitedActivityMiltefosine.pdf
Size:
821.18 KB
Format:
Adobe Portable Document Format
Download

Collections

UT Faculty/Researcher Works