Parallel-resistance of azoles and echinocandines and their cross-resistance to flucytosine and amphotericin B in clinical yeast isolates

Schmalreck A., Becker K., Fegeler W.

Author address: 



Objectives: To evaluate the parallel-resistance (PR) of azoles (AZs) (fluconazole, FL; itraconazole, IT; voriconazole, VO; posaconazole, PO) and echinocandines (ECs) (caspofungin, CA; anidulafungin, AN) and their cross-resistance (CR) to flucytosine (FC) and amphotericin B (AM), the minimum inhibitory concentrations (MICs) of 1,355 clinical yeast isolates (CYIs) were analyzed by susceptibility pattern analysis (SPA). Methods: Testing of CYIs was performed by Etest® -strips on modified RPMI agar with 2% glucose and 0.5 mg methylene blue/L. All antifungal agents (AFAs) were tested in parallel from the same inoculum (10^5cfu/ml). SPAs of the individual susceptibility results for each AFA in each isolate were performed and the results were aligned to individual susceptibility patterns (SPs). Results: The CYIs comprised 9 genera: Candida (1266/93.4%, comprising 749 C. albicans, 358 C. glabrata, 88 C. tropicalis, 49 C. parapsilosis and 22 isolates of other species), Clavispora (11/0.8%), Magnusiomyces (8/0.6%), Filobasidiella (2/0.2%), Issatchenkia (29/2.0%), Kluyveromyces (15/1.1%), Pichia (10/0.7%), Saccharomyces (13/0.9%), and Trichosporon (1/0.1%). The percentage of resistant isolates differed considerably depending on the AFA and on the MIC-reading time (24 h vs. 48 h): FC, 8.6 vs. 11; AM, 0.6 vs. 4.9; FL, 5.9 vs. 19.4; IT, 27.7 vs. 33.5; VO, 2.2 vs. 6.5; PO, 15.1 vs. 27.6; CA, 1.6 vs. 3.5; AN, 3.1 vs. 4.8. The species-specific resistance rates (RRs) demonstrated large variations showing RRs for ECs of C. dubliniensis, C. parapsilosis, and Pichia from 10% to 85% and RRs for AZs of C. glabrata, Issatchenkia, and Pichia from 20% to 90%. CR of the AZs and ECs tested to FC and AM was not found in any isolate, even after 48 h of incubation. According to 24 h vs. 48 h incubation, 28 vs. 79 isolates showed complete PR to AZs (C. glabrata, 25 vs. 53; C. albicans, 2 vs. 23) and 776 (57.3%) vs. 681 (50.3%) strains exhibited susceptibility to all antifungals tested. PR with ECs was recorded in 18 (1.3%) vs. 29 (2.1%) of the strains. Conclusion: The MIC differences and the one-sided PR of the azoles underline the importance of analyzing the routine-results with different comparative analyzing tools. Susceptibility determination of AFA was found to be strongly species- and endpoint-reading dependent. Consequently, species-specific breakpoints for these agents should be established in order to achieve reliable in vitro results and qualified therapy recommendations.

abstract No: 

P 1301

Full conference title: 

19th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 19th (2009)