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Exploring the In Vitro Resistance of Candida parapsilosis to Echinocandins
Francieli Chassot1,2, Tarcieli Pozzebon Venturini3, Fernanda Baldissera Piasentin3
1Health Sciences Centre, Federal University of Santa Maria, Santa Maria, RS, Brazil. francielichassot@gmail.com.
Abstract:
The naturally high minimum inhibitory concentration exhibited by echinocandins against Candida parapsilosis has been known since the first introduction of these antifungal agents. Despite this awareness, clinical failures have not been reported; consequently, the resistance of C. parapsilosis to echinocandins remains unexplored. We exposed 30 isolates of C. parapsilosis to echinocandins (caspofungin, micafungin, and anidulafungin) in vitro and studied the effects of this exposure. After 60 exposures, 80, 67, and 60 % of the isolates changed from susceptible to non-susceptible to caspofungin, micafungin, and anidulafungin, respectively. In addition, four strains exhibited cross-resistance to all three echinocandins. Based on the M27-A3 (CLSI, 2008) and M27-S4 (CLSI, 2012) techniques, the susceptibility of the resistant strains to other antifungal agents was assayed. All of the tested echinocandin-resistant strains were susceptible to amphotericin B, and the resistance rate to fluconazole, voriconazole, and flucytosine was 73.3, 43.3, and 20 %, respectively. The exposure of C. parapsilosis to the three echinocandins generated cross-resistant strains and an unexpected in vitro resistance to azoles and flucytosine.
Insights
Candida parapsilosis developed resistance to echinocandin antifungal drugs after repeated exposure. This study reveals emerging resistance to caspofungin, micafungin, and anidulafungin, alongside cross-resistance to other antifungals.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Echinocandins are crucial antifungal agents, but Candida parapsilosis exhibits naturally high minimum inhibitory concentrations.
- Despite known high MICs, clinical failures linked to echinocandin resistance in C. parapsilosis have not been widely reported, leaving resistance mechanisms unexplored.
Purpose of the Study:
- To investigate the in vitro development of echinocandin resistance in Candida parapsilosis isolates.
- To assess the emergence of cross-resistance to other antifungal agents following echinocandin exposure.
Main Methods:
- Exposing 30 Candida parapsilosis isolates to echinocandins (caspofungin, micafungin, anidulafungin) over 60 passages in vitro.
- Assaying the susceptibility of resistant strains to other antifungal agents (amphotericin B, fluconazole, voriconazole, flucytosine) using CLSI M27-A3 and M27-S4 techniques.
Main Results:
- Significant proportions of isolates developed non-susceptibility to caspofungin (80%), micafungin (67%), and anidulafungin (60%) after repeated exposure.
- Four strains exhibited cross-resistance to all three echinocandins.
- Echinocandin-resistant strains remained susceptible to amphotericin B, but showed high resistance rates to fluconazole (73.3%), voriconazole (43.3%), and flucytosine (20%).
Conclusions:
- Repeated in vitro exposure to echinocandins can induce resistance in Candida parapsilosis.
- This induced resistance can lead to cross-resistance not only among echinocandins but also unexpectedly to azoles and flucytosine.
- The findings highlight the potential for echinocandin resistance to emerge in C. parapsilosis and necessitate further investigation into clinical implications.
