Comparison of CLSI and EUCAST Antifungal Susceptibility Profile with Therapeutic Outcome in HIV-positive Cryptococcosis Patients Due to Cryptococcus neoformans var. grubii in India

S. Kathuria, A. Prakash, J. F. Meis, A. Chowdhary

Author address: 

Vallabhbhai Patel Chest Inst., Univ. of Delhi, Delhi, INDIA; Canisius Wilhelmina Hosp., Nijmegen, NETHERLANDS; Radboud Univ. Nijmegen Med. Ctr., Nijmegen, NETHERLANDS.


Background: To report comparison between CLSI and EUCAST antifungal susceptibility testing of C. neoformans var. grubii from 45 HIV-positive Indian patients with their therapeutic outcome. Materials and methods: From 2008 through 2012, 45 patients with culture proven cryptococcosis were included in a prospective study. Of 96 isolates, 75 originated from CSF, 9 blood, 8 sputum, 2 urine and one from a bronchial aspirate. Twenty nine patients received combination of amphotericin B and fluconazole whereas 16 patients in addition received flucytosine. Genotyping was done with AFLP and microsatellite typing. Susceptibility was determined for amphotericin B (AMB), flucytosine (FC), fluconazole (FLU), voriconazole (VRC), posaconazole (POS), isavuconazole (ISA) and itraconazole (ITC) by CLSI and EUCAST methods. Statistical differences between mean MICs of CLSI and EUCAST were assessed, using Student’s t-test. Discrepancies of more than two dilutions among MIC results were used to calculate the Essential agreement. Results: Microsatellite typing of 96 C. neoformans var. grubii AFLP1/VNI, showed that the majority belonged to microsatellite cluster (MC) MC1 (n=64;66%), followed by MC3 (n=21;22%) and MC2 (n=8;8.3%). Three (3.1%) isolates could not be linked to known MC. All isolates showed goodin vitro activities for all antifungals except two which had high MICs of FC. The mean MICs were significantly higher by CLSI for AMB, (P=0.0001), ITC (P=0.035) and POS (P=0.003) whereas by EUCAST for FLU (P=0.022) and VRC (P=0.001). Essential agreement between two methods was highest for VRC (94.5%) followed by FLU (89%), ITC (89%), AMB (87.3%), POS (82%), and FC (70%). The mortality rates were equal in both treatment groups with higher fatalities among patients with disseminated cryptococcosis Conclusions: This is the first study comparing the CLSI and EUCAST methods for C. neoformans var. grubii. There was good concordance (97% EA) between the two methods. Two microsatellite types dominate in India and exhibit low MICs for FLU and AMB. The low MICs were associated with successful treatment in 67% of cases.

abstract No: 


Full conference title: 

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC, 53rd (2013)