BACHMANN SP, PEREA S, KIRKPATRICK WR, PATTERSON TF, LOPEZ-RIBOT JL; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 352.
Univ. of Texas Health Sci. Ctr., San Antonio, TX
BACKGROUND: Cancidas is a fungicidal, water-soluble semisynthetic echinocandin that inhibits synthesis of 1,3-b-D glucan, a key step in the fungal cell wall biosynthesis. Because their different mode of action and molecular structure, it is very unlikely that cross-resistance between azoles (targeting ergosterol synthesis) and echinocandins occurs.METHODS: C. albicans isolates were recovered from 11 patients who developed fluconazole resistance. DNA-typing techniques were used to determine strain identity. Expression of genes encoding lanosterol demethylase (ERG11) and multidrug efflux pumps (MDR and CDR) was monitored in matched sets of fluconazole susceptible (n=11) and resistant (n=19) isolates. The nucleotide sequences of ERG11 genes were determined. Susceptibility testing against Cancidas and clinically used fluconazole, itraconazole and amphotericin B was performed by NCCLS techniques using a broth microdilution method and reading of endpoints at 24 and 48 h. For Cancidas, both RPMI 1640 and Antibiotic Medium 3 (AM3) were used as test media.RESULTS: Cancidas demonstrated high efficacy against all C. albicans isolates tested, with 48h MICs ranging from 0.25 to 2 microg/ml in RPMI medium (mean=0.587 microg/ml) and = 0.015 to 0.03 microg/ml in AM3 (mean=0.015 microg/ml). These included azole-resistant isolates where overexpression of ERG11 or point mutations in the ERG11 genes were detected but also isolates overexpressing multidrug efflux pumps. Conclusion: Cancidas is highly active against azole resistant isolates irrespective of the underlying molecular mechanism(-s) of azole resistance and may constitute an effective therapeutic option for the treatment of C. albicans infections. This study also confirms differences in Cancidas MIC values according to test medium.KEYWORDS: Candida spp.; Echinocandin; Efficacy
Publication Types:
Keywords:
- Amphotericin B
- Antifungal Agents
- Antigens, Fungal
- Azoles
- Candida
- Candida albicans
- Candidiasis
- Case-Control Studies
- Ergosterol
- Fluconazole
- Fungi
- Humans
- In Vitro
- Itraconazole
- Microbial Sensitivity Tests
- Peptides, Cyclic
- caspofungin
- immunology
Other ID:
UI: 102247009
From Meeting Abstracts