Fluconazole and itraconazole susceptibility of clinical isolates of Cryptococcus neoformans at a tertiary care centre in India:: a need for care

Objectives: In cryptococcosis, fluconazole is a standard prophylactic, therapeutic and maintenance option, particularly in the expanding HIV/AIDS group. However, its excessive use may lead to resistance in Cryptococcus neoformans. Variations in clinical response to fluconazole have already been noted elsewhere, and cases of post-therapy relapse are not uncommon. To assess azole antifungal susceptibility profiles of clinical cryptococcal isolates in India, the All India Institute of Medical Sciences (AIIMS) has recently initiated preliminary studies using NCCLS M27-A. Materials and methods: Twenty-eight randomly chosen AIIMS clinical isolates (spanning 1997-2000), 16 isolates from other institutions in North India, and six reference strains of C. neoformans were subjected to susceptibility testing to fluconazole and itraconazole. Results: Among clinical isolates, susceptibilities to fluconazole and itraconazole were 84.1% and 93.2%, respectively. MICs for all clinical isolates were 0.25-32 mg/L for fluconazole and <0.03-0.25 mg/L for itraconazole. MIC50 and MIC90 values for fluconazole were 4 and 16 mg/L, respectively, and those for itraconazole were 0.032 and 0.125 mg/L, respectively. Out of 28 AIIMS clinical isolates, 22 had minimum fungicidal concentrations (MFCs) of fluconazole at greater than or equal to128 mg/L. Moderately high fluconazole MICs (16-32 mg/L) were observed in 16% of clinical isolates-probably the first such report from India. MIC/MFC ratios for fluconazole and itraconazole were 1:32 or more in 16 AIIMS clinical isolates, indicating possible azole tolerance. There was good agreement between MIC values obtained by the micro- and macro-broth dilution techniques of M27-A compared in this study. Conclusions: The observed MIC data warrant continued surveillance of susceptibility values of clinical cryptococcal isolates in India.