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dc.creatorWiederhold, Nathan P.en
dc.creatorNajvar, Laura K.en
dc.creatorBocanegra, Rosie A.en
dc.creatorKirkpatrick, William R.en
dc.creatorPatterson, Thomas F.en
dc.date.accessioned2015-09-09T15:51:50Zen
dc.date.available2015-09-09T15:51:50Zen
dc.date.issued2011-07en
dc.identifier.citationWiederhold, N. P., Najvar, L. K., Bocanegra, R. A., Kirkpatrick, W. R., & Patterson, T. F. Caspofungin Dose Escalation For Invasive Candidiasis Due To Resistant Candida Albicans. Antimicrobial Agents and Chemotherapy, (Jul., 2011) 55(7), 3254-3260. DOI: 10.1128/aac.01750-10en
dc.identifier.issn0066-4804en
dc.identifier.urihttp://hdl.handle.net/2152/31264en
dc.description.abstractPrevious in vivo studies have reported caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 -> 3)-beta-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 -> 3)-beta-D-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1 -> 3)-beta-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain.en
dc.description.sponsorshipen
dc.language.isoEnglishen
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.subjectreduced echinocandin susceptibilityen
dc.subjectdouble-blind trialen
dc.subjectamphotericin-ben
dc.subjectin-vitroen
dc.subjectaspergillus-fumigatusen
dc.subjectmicafungin fk463en
dc.subjectadult patientsen
dc.subjectimmune-systemen
dc.subjectmurine modelen
dc.subjectglabrataen
dc.subjectmicrobiologyen
dc.subjectpharmacology & pharmacyen
dc.titleCaspofungin Dose Escalation For Invasive Candidiasis Due To Resistant Candida Albicansen
dc.typeArticleen
dc.rights.holderen
dc.description.departmentPharmacyen
dc.identifier.doi10.1128/aac.01750-10en
dc.identifier.urlen
dc.contributor.utaustinauthorWiederhold, Nathan P.en
dc.relation.ispartofserialAntimicrobial Agents and Chemotherapyen


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