Differential Activities of Newer Antifungal Agents against Candida albicans and Candida parapsilosis Biofilms

Abstract

The activities of voriconazole, posaconazole, caspofungin, and anidulafungin against Candida albicans and Candida parapsilosis biofilms were evaluated. In contrast to planktonic cells, the MICs for voriconazole and posaconazole for the biofilms of the two species were high (>256 and >64 mg/liter, respectively) but relatively low for the echinocandins caspofungin and anidulafungin (<1 and <2 mg/liter, respectively).Candida spp. have frequently been associated with the formation of biofilms on biological and inert surfaces, such as intravascular catheters (15). Candida albicans and Candida parapsilosis are the most prevalent species related to the biofilm mode of growth (12). Resistance of Candida biofilms to conventional antifungal agents has been previously documented (2, 10, 16). Given that biofilm-associated infections are very difficult to cure without device removal, the demand for newer, more effective therapies has been developed.The goal of the present study was to examine the activities of newer antifungal agents against C. albicans and C. parapsilosis biofilms and compare them to their corresponding planktonic cells. Voriconazole (VRC; Pfizer, Groton, CT), posaconazole (PSC; Schering-Plough, Kenilworth, NJ), caspofungin (CAS; Merck, Whitehouse Station, NJ), and anidulafungin (AND; Pfizer), were examined.Documented biofilm-producing strains were used, including C. albicans M61, C. albicans GDH2346, and C. parapsilosis PA/71 (4, 5). Aliquots were maintained in 25% glycerol and 75% peptone at Ϫ35°C.Planktonic MICs were determined according to the Clinical and Laboratory Standards Institute M27-A2 method. MICs were determined as the lowest drug concentrations at which a prominent decrease in turbidity was observed, corresponding to ca. 50% inhibition in growth (8-10, 13). The MICs were recorded after incubation for 24 h.Biofilm MIC determination was based on modifications of methods previously described (5, 10, 16). Biofilms were grown on the surface of silicone elastomer disks (Bioplexus Corp., Saticoy, CA), pretreated with fetal bovine serum (Gibco, Paisley, Scotland), in 12-or 96-well plates for 48 h for C. albicans strains and 72 h for C. parapsilosis. In an effort to make our adopted model resemble in vivo conditions, organisms were grown on the surface of a silicone substrate coated with a fetal bovine serum-conditioning film under constant linear shaking (4). Mature biofilms were then incubated in RPMI 1640 containing VRC, PSC, CAS, or AND at doubling dilutions ( Fig. 1 and 2) for 24 h. Drugfree biofilms containing only RPMI 1640 served as controls. Four replicate biofilms were used for each condition. Biofilm MICs were determined as the minimum antifungal drug concentrations that caused Ն50% reduction in the metabolic activity of the biofilms compared to controls (10). Biofilm formation and antifungal activities were assessed by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide (XTT; 0.25 mg/ml) and coenzyme Q (40 g/ ml) assay spectrophotometrically at 450 nm with a reference wa...

Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin

“…Similarly to our study, the data of Jacobson et al (2008) showed the SMIC 50 for anidulafungin to be ¡0.03125 mg ml 21 in 28 of 30 C. albicans clinical isolates tested when the biofilm was formed in RPMI 1640 medium. In contrast to the work of Katragkou et al (2008), we did not observe any indication of paradoxical growth during caspofungin activity against a mature C. albicans biofilm, even when high concentrations (4-8 mg ml 21 ) of the drug were administered to biofilms (data not shown). C. glabrata cells forming mature biofilm were less susceptible than the diploid species to caspofungin and anidulafungin in both media tested, albeit with up to half the thickness of C. albicans biofilms.…”

“…However, caspofungin and anidulafungin were shown to have activity on mature C. albicans biofilms in vitro (Katragkou et al, 2008;Pemán et al, 2008) and in vivo (Shuford et al, 2006;Kucharíková et al, 2010a). Caspofungin was also shown to be active against mature C. glabrata biofilms formed in vitro (Choi et al, 2007).…”

Candida parapsilosis, an Emerging Fungal Pathogen

“…21,2008 CANDIDA PARAPSILOSIS 615 on May 11, 2018 by guest http://cmr.asm.org/ resistant as C. albicans biofilm to conventional antifungals, such as amphotericin B and azole compounds, (131,238). However, therapeutic levels of echinocandins can inhibit metabolic activities of C. parapsilosis biofilms (50,131,146), and lipid formulations of amphotericin B have shown activity against C. parapsilosis biofilm (146). Farnesol is a quorum-sensing agent in C. albicans that inhibits biofilm formation as well as filamentation (115,225).…”

Transcription factor Efg1 contributes to the tolerance of Candida albicans biofilms against antifungal agents in vitro and in vivo

“…Upon contact with various surfaces, C. albicans is known to form biofilms, which are a cause of infections associated with medical devices such as indwelling intravascular catheters. Those infections are particularly serious because biofilm-associated Candida cells display increased tolerance to a wide spectrum of antifungal drugs, including various azoles, such as fluconazole (MIC 50 ¢256 mg l 21 ) and miconazole (MIC 50 ¢256 mg l 21 ), and the newer generation of azoles, such as voriconazole (MIC 50 ¢256 mg l 21 ) and posaconazole (MIC 50 ¢64 mg l 21 ) (Lamfon et al, 2004;Ramage et al, 2009;Katragkou et al, 2008). Miconazole has moderate fungicidal activity against C. albicans biofilms, as 1-10 % sessile C. albicans cells can survive exposure to high doses (2080 mg l 21 ) of miconazole (Vandenbosch et al, 2010).…”