title: Characterization of caspofungin susceptibilities by broth and agar in Candida albicans clinical isolates with characterized mechanisms of azole resistance.
abstract: Caspofungin (CSP) susceptibilities of Candida albicans, as determined by broth microdilution methods, have not been found to be related to azole susceptibilities or resistance. In contrast, it has been observed that azole-resistant clinical isolates that overexpress the efflux pump gene CDR2 are less susceptible to CSP when tested using an agar dilution method commonly employed with Saccharomyces cerevisiae. The goal of this study was to further understand the effects of azole resistance mechanisms on CSP susceptibility testing. A collection of 69 isolates exhibiting known mechanisms of azole resistance and resistance-associated phenotypes were analyzed by broth microdilution methods to determine standard minimum inhibitory concentrations (MICs) for CSP. The same isolates were then analyzed as to their MIC to CSP by Etest strips, an agar-based method that has been shown generally to be comparable to broth methods. The MICs found with both methods were not significantly different. However, a collection of strains overexpressing the efflux pump CDR2 did exhibit a spectrum of CSP susceptibilities when examined by agar dilution susceptibility tests, ranging from standard to reduced susceptibilities. This work demonstrated that a change in CSP susceptibility with CDR2 overexpressing cells in agar dilution studies is a variable phenotype and it is not the result of growth conditions (i.e., broth versus agar).
authors.affiliation: Department of Pathobiology, School of Public Health and Community Medicine, University of Washington and Seattle Biomedical Research Institute, Seattle, Washington 98109-5219, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Silver
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.forename: Theodore C
authors.initials: TC
authors.lastname: White
mesh_terms: D000362:Agar / Q000032:analysis; D000935:Antifungal Agents / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002177:Candidiasis / Q000382:microbiology*; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides; D008668:Metallothionein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D001393:Azoles; C413336:Crd2 protein, Candida albicans; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D000362:Agar; D008668:Metallothionein; D000077336:Caspofungin