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Lack of correlation of 24‐ vs. 48‐h itraconazole minimum inhibitory concentrations with microbiological and survival outcomes in a guinea pig model of disseminated candidiasis
Author(s) -
Odabasi Zekaver,
Paetznick Victor L.,
Rodriguez Jose R.,
Chen Enuo,
Rex John H.,
Leitz Gerhard J.,
OstroskyZeichner Luis
Publication year - 2010
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1111/j.1439-0507.2009.01733.x
Subject(s) - itraconazole , fluconazole , minimum inhibitory concentration , azole , microbiology and biotechnology , dosing , mycosis , biology , pharmacology , medicine , antifungal , antibiotics , immunology
Summary A ‘trailing’ effect has been commonly observed when azole antifungals are tested against Candida spp. Previous experience with fluconazole indicates that 24‐h minimum inhibitory concentration (MIC) values are more compatible endpoints when compared with clinical outcomes. We evaluated the trailing effect of Candida isolates tested with itraconazole in a guinea pig model of systemic candidiasis. Survival and organ burden were only significantly affected by using a higher dose of itraconazole, irrespective of the MIC differences at 24 and 48 h. A fluconazole‐resistant strain with susceptible dose‐dependent MICs to itraconazole was successfully treated with high‐dose itraconazole. Our data suggests that survival and microbiological response depend more on drug dosing than on the trailing phenotype of the isolates.