title: 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.
abstract: 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.
authors.affiliation: Laboratory of Mycology Research, Division of Infectious Diseases, University of Texas, Houston Medical School, Houston, TX, USA. zekaver@marmara.edu.tr
authors.forename: Zekaver
authors.initials: Z
authors.lastname: Odabasi
authors.forename: Victor L
authors.initials: VL
authors.lastname: Paetznick
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez
authors.forename: Enuo
authors.initials: E
authors.lastname: Chen
authors.forename: John H
authors.initials: JH
authors.lastname: Rex
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Leitz
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D015725:Fluconazole