Comparative analysis of antifungal susceptibility testing methods for echinocandins in candidemia isolates

Abstract

Background: The alarming rise in antifungal resistance during therapy, increased use of antifungals and the recognition of innate resistance in some fungal species has led to greater demand for antifungal susceptibility testing (AFST). Candida spp. are the most prevalent invasive fungal infections. Also, each species has its unique virulence potential, epidemiology and antifungal susceptibility patterns. One of the novel species, Candida auris (first described in 2009) has emerged as a cause of rapidly spreading nosocomial outbreaks, further it has reduced susceptibility to the major classes of antifungal agents. Our objective is to analyse various methods of AFST for testing MIC (Minimum inhibitory concentration) of echinocandins in candidemia isolates. Methods and materials: This study was conducted at Medanta-The Medicity, Haryana, India. We performed three methods of AFST on each of the 100 clinical bloodstream Candida isolates which were identified by Matrix Assisted Laser Desorption Ionization-Time of Fight Mass Spectrometry (MALDI-TOF MS) (Bruker Daltonics). The methods performed for detecting MIC of antifungal agents included VITEK 2 (bioMérieux), Etest (bioMérieux) and CLSI (Clinical and Laboratory Standards Institute) Broth Microdilution (BMD) following the M27-A3 guidelines. The echinocandins tested were caspofungin and micafungin. Results: Nonalbicans Candida (70/100) were more frequently isolated as compared to Candida albicans (30/100). The nonalbicans detected were Candida auris (28/70) followed by Candida tropicalis (24/100) and others. The MIC range of Caspofungin with VITEK 2, CLSI BMD and Estrip respectively for Candida albicans and Candida tropicalis (similar) ≤0.25–0.5, 0.03–0.125, 0.06–0.08; for Candida auris ≤0.25–0.5, 0.5–1, 0.5–1. Similarly, the MIC range of micafungin with VITEK 2, CLSI BMD and Estrip respectively for Candida albicans and Candida tropicalis ≤0.06–0.5, 0.03–0.06, 0.064–0.125; for Candida auris 0.12, 0.06–0.125, 0.064–0.125. The results suggest that the CLSI BMD and Estrip give similar results while Vitek 2 deviates, but the variation is not statistically significant. Conclusion: The clinical laboratories should have a clear approach about which method of AFST is feasible, reliable and cost effective to their setting. Identification of Candida to the species level and AFST helps in prompt management of difficult-to-treat cases of invasive candidiasis. Furthermore, epidemiological studies should also be done periodically to determine the antifungal resistance rates for individual centres.