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

Abstract

e Candida species other than Candida albicans are increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared the in vitro activities of all three echinocandins against biofilms formed by different common and infrequently identified Candida isolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates of C. albicans (15 strains), Candida parapsilosis (6 strains), Candida lusitaniae (16 strains), Candida guilliermondii (5 strains), and Candida 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 all Candida species 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 the Candida species. Thus, C. lusitaniae and C. guilliermondii biofilms were highly recalcitrant to all echinocandins, with MICs of >32 mg/ liter. In contrast, the MICs of all three echinocandins for C. albicans and C. krusei biofilms were relatively low (MICs < 1 mg/ liter). While echinocandins exhibited generally high MICs against C. parapsilosis biofilms, 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 against C. albicans and C. parapsilosis biofilms but not against C. krusei, C. lusitaniae, or C. guilliermondii. While nonalbicans Candida planktonic cells were susceptible to all echinocandins, there were drug-and species-specific differences in susceptibility among biofilms of the various Candida species, with C. lusitaniae and C. guilliermondii exhibiting profiles of high MICs of the three echinocandins.

Caspofungin at Catheter Lock Concentrations Eradicates Mature Biofilms of Candida lusitaniae and Candida guilliermondii

“…With the exception of the planktonic MIC of ANID for C. guilliermondii that was six 2-fold dilutions (64-fold) higher than the corresponding MIC for C. albicans M61, the MICs of all four antifungal agents against planktonic cells of the Candida species studied displayed good in vitro activity with comparable susceptibility profiles (Table 1, 0.06 to 1 mg/liter), as also previously documented by us and others (13,14,18,19). However, mature biofilms of C. lusitaniae and C. guilliermondii showed higher MICs to the three echinocandins than their corresponding planktonic cells ( Table 1; P Ͻ 0.01).…”

“…While Candida biofilms are generally recalcitrant to conventional antifungal agents, liposomal amphotericin B and echinocandins have demonstrated good antibiofilm activities which are both species and drug specific (10)(11)(12)(13)(14). Candida lusitaniae and Candida guilliermondii are known to have relatively high MICs to echinocandins (10,13,14) that may create greater challenges in eradication of their biofilms from vascular catheters (15).…”

“…Candida lusitaniae and Candida guilliermondii are known to have relatively high MICs to echinocandins (10,13,14) that may create greater challenges in eradication of their biofilms from vascular catheters (15). We have previously shown that caspofungin at high concentrations (Ն64 mg/liter) was able to cause damage to the highly recalcitrant biofilm structures of C. lusitaniae and C. guilliermondii by 70% to 96% (14). These findings indicated that caspofungin could be an effective agent for antifungal lock therapy, especially against C. lusitaniae and C. guilliermondii.…”

“…C. guilliermondii and C. lusitaniae strains were isolated from catheter-associated bloodstream infections (14) and C. albicans M61 from an infected intravascular catheter (12). Anidulafungin (Pfizer), caspofungin (Merck), micafungin (Astellas), and liposomal amphotericin B (Gilead) were obtained from their manufacturers.…”

Micafungin at Physiological Serum Concentrations Shows Antifungal Activity against Candida albicans and Candida parapsilosis Biofilms

“…Recent in vitro and in vivo models designed to assess the antifungal susceptibility of Candida biofilms (19,21,(23)(24)(25)(26)(27)(28)(29) showed that the echinocandins, particularly micafungin, had the highest antifungal activities (30)(31)(32)(33)(34). However, the studies are limited by the inclusion of a low number of clinical isolates; furthermore, the concentration of antifungal necessary to inactivate sessile cells is unknown.…”