In Vitro Activity of Anidulafungin against Candida albicans Biofilms

Abstract

We tested the activity of anidulafungin against 30 Candida albicans isolates. The planktonic MICs for 50 and 90% of the isolates tested (MIC 50 and MIC 90 ) were <0.03 and 0.125 g/ml, respectively (MIC range, <0.03 to 2 g/ml). The sessile MIC 50 and MIC 90 were <0.03 and <0.03 g/ml, respectively (MIC range, <0.03 to >16 g/ml).Candida albicans infections seen in modern clinical practice, such as device-and intravascular catheter-related infections (2, 5), are associated with the growth of organisms in a biofilm state. Device removal is often necessary for a cure (7) since antimicrobials have traditionally been considered to be poorly active against microorganisms in biofilms. If, however, antimicrobials are active against microbial biofilms, device removal may be unnecessary. It has been proposed that antifungal agents that target cell wall synthesis may be active against C. albicans biofilms (1).We recently determined the in vitro antifungal activities of caspofungin and voriconazole against 30 clinical C. albicans isolates in their planktonic and sessile states. Susceptibility testing of the isolates in their planktonic and sessile forms revealed a marked rise in the voriconazole MIC for 90% of the isolates tested (MIC 90 ), which was much less marked for caspofungin (8). We also demonstrated that caspofungin was active in vivo in an experimental intravascular catheter infection model (9). Recently, Choi et al. reported that micafungin was active against biofilms formed by C. albicans (3), and Katragkou et al. reported that anidulafungin was active against two C. albicans strains in the biofilm state (6). The purpose of this study was to determine the in vitro activity of anidulafungin against our collection of C. albicans (8) grown in planktonic and sessile states.Thirty C. albicans clinical isolates obtained from sterile-site infections from October 2003 through October 2004 were studied (8). One isolate per patient was studied. Ten isolates were from blood cultures, including eight from patients with central venous catheters. The other 20 isolates were from peritoneal fluid (n ϭ 6), abscess fluid (n ϭ 5), soft tissue (n ϭ 5), bone (n ϭ 2), and pleural fluid and urine (n ϭ 1 each). C. albicans GDH2346 was used as a positive control. Anidulafungin concentrations ranging from 16 to 0.03 g/ml were tested.Planktonic MICs were determined by Clinical and Laboratory Standards Institute broth microdilution methods (4). The lowest concentration associated with a significant reduction in turbidity compared with the control well at 48 h was reported as the MIC (4). Isolates for which the MICs were Ͼ0.125 g/ml were retested and read at 24 and 48 h, as others have reported MICs after 24 h (6).Sessile MICs were determined with biofilms formed in 96-well flat-bottom microtiter plates as previously described (8). Yeast cells were grown overnight in yeast nitrogen base medium, washed twice in sterile phosphate-buffered saline (PBS), and standardized to 1 ϫ 10 7 CFU/ml in RPMI medium. Each well was filled with 100 l C. albican...

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).…”

In Vitro Activity of Micafungin against Planktonic and Sessile Candida albicans Isolates

“…Overall, anidulafungin was the most potent agent against C. albicans biofilms; the anidulafungin SMIC was previously determined to be Յ0.03 g/ml for 28/30 isolates (7). However, the remaining two isolates had anidulafungin SMIC values of Ͼ16 g/ml, one having the highest planktonic anidulafungin MIC (2 g/ml) observed (7). The two isolates with anidulafungin SMICs of Ͼ16 g/ml had caspo-fungin SMICs of Յ0.25 g/ml and micafungin SMICs of 0.25 g/ml (7,12).…”

In Vitro Activities of Anidulafungin and Other Antifungal Agents against Biofilms Formed by Clinical Isolates of Different Candida and Aspergillus Species

“…A recent study exploring the early transcriptional responses of mature Candida albicans biofilm exposed to various antifungal agents suggests that enhanced extracellularmatrix or beta-glucan synthesis during biofilm growth (18) might prevent fluconazole and amphotericin B from reaching biofilm cells, thus impairing their cell toxicity and the associated transcriptional responses (27). As echinocandins are noncompetitive inhibitors of beta-glucan synthesis (20), this may explain why the drugs have been shown to be effective against Candida biofilms (4,8,9,11,28). In another study, liposomal formulation of amphotericin B was shown to eradicate C. albicans biofilm in a continuous catheter flow model, whereas fluconazole and caspofungin were less effective (24).…”