Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates

Abstract

ABSTRACTCandidaspecies other thanCandida albicansare increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared thein vitroactivities of all three echinocandins against biofilms formed by different common and infrequently identifiedCandidaisolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates ofC. albicans(15 strains),Candida parapsilosis(6 strains),Candida lusitaniae(16 strains),Candida guilliermondii(5 strains), andCandida krusei(12 strains) by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. Planktonic and biofilm MICs were defined as ≥50% fungal damage. Planktonic cells of allCandidaspecies were susceptible to the three echinocandins, with MICs of ≤1 mg/liter. By comparison, differences in the MIC profiles of biofilms in response to echinocandins existed among theCandidaspecies. Thus,C. lusitaniaeandC. guilliermondiibiofilms were highly recalcitrant to all echinocandins, with MICs of ≥32 mg/liter. In contrast, the MICs of all three echinocandins forC. albicansandC. kruseibiofilms were relatively low (MICs ≤ 1 mg/liter). While echinocandins exhibited generally high MICs againstC. parapsilosisbiofilms, MFG exhibited the lowest MICs against these isolates (4 mg/liter). A paradoxical growth effect was observed with CAS concentrations ranging from 8 to 64 mg/liter againstC. albicansandC. parapsilosisbiofilms but not againstC. krusei,C. lusitaniae, orC. guilliermondii. While non-albicans Candidaplanktonic cells were susceptible to all echinocandins, there were drug- and species-specific differences in susceptibility among biofilms of the variousCandidaspecies, withC. lusitaniaeandC. guilliermondiiexhibiting profiles of high MICs of the three echinocandins.