Abstract

This study analyzed the in vitro drug sensitivity of Cryptococcus spp. from Guangxi, Southern China. One hundred three strains of Cryptococcus were recovered from 86 patients; 14 were HIV positive and 72 were HIV negative. Ninety-two strains were identified as Cryptococcus neoformans var. grubii, while 11 strains were identified as Cryptococcus gattii (5 C. gattii sensu stricto and 6 Cryptococcus deuterogattii). The recovered strains were tested against commonly used antifungal drugs (fluconazole, amphotericin B, 5-fluorocytosine, itraconazole, and voriconazole) and to novel antifungal drugs (posaconazole and isavuconazole) using CLSI M27-A4 method. The results showed that all isolates were susceptible to most antifungal drugs, of which the minimum inhibitory concentration (MIC) ranges were as follows: 0.05–4 μg/ml for fluconazole, 0.25–1 μg/ml for amphotericin B; 0.0625–2 μg/ml for 5-fluorocytosine, 0.0625–0.25 μg/ml for itraconazole, 0.0078–0.25 μg/ml for voriconazole, 0.0313–0.5 μg/ml for posaconazole, 0.0020–0.125 μg/ml for isavuconazole for C. neoformans var. grubii isolates, and 1–16 μg/ml for fluconazole, 0.125–1 μg/ml for 5-fluorocytosine, 0.25–1 μg/ml for amphotericin B, 0.0625–0.25 μg/ml for itraconazole, 0.0156–0.125 μg/ml for voriconazole, 0.0156–0.25 μg/ml for posaconazole, and 0.0078–0.125 μg/ml for isavuconazole for C. gattii isolates. Furthermore, some C. neoformans var. grubii isolates were found to be susceptible-dose dependent to 5-fluorocytosine and itraconazole. In addition, a reduction in the potency of fluconazole against C. gattii is possible. We observed no statistical differences in susceptibility of C. neoformans var. grubii and C. gattii in the tested strains. Continuous observation of antifungal susceptibility of Cryptococcus isolates is recommended to monitor the emergence of resistant strains.

Highlights

  • Cryptococcosis is a common opportunistic invasive fungal infection caused mainly by Cryptococcus neoformans (C. neoformans, serotypes A, AD, and D) and Cryptococcus gattii (C. gattii serotypes B and C) (Guinea et al, 2010)

  • The incidence of cryptococcosis has declined with the introduction of highly active antiretroviral therapy (HAART), immunocompromised individuals remain at risk, and mortality rate remain unacceptably high despite the continued research on cryptococcosis (Park et al, 2009; Selb et al, 2019)

  • C. neoformans var. grubii The minimum inhibitory concentration (MIC) ranges of the 92 C. neoformans var. grubii strains for the 7 drugs were as follows: FLC, 0.05–4 μg/ml; amphotericin B (AmB), 0.25– 1 μg/ml; 5-FC, 0.0625–2 μg/ml; ITC, 0.0625–0.25 μg/ml; VOC, 0.0078–0.25 μg/ml; POS, 0.0313–0.5 μg/ml; and ISA, 0.0020– 0.125 μg/ml

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Summary

Introduction

Cryptococcosis is a common opportunistic invasive fungal infection caused mainly by Cryptococcus neoformans (C. neoformans, serotypes A, AD, and D) and Cryptococcus gattii (C. gattii serotypes B and C) (Guinea et al, 2010). The latter mainly affects otherwise healthy individuals, whereas C. neoformans is more common in immunocompromised patients (Park et al, 2009; Guinea et al, 2010; Maziarz and Perfect, 2016). New antifungal agents have been introduced, suggesting that the Abbreviations: FLC, fluconazole; AmB, amphotericin B; ITC, itraconazole; 5-FC, 5-flucytosine; VOC, voriconazole; POS, posaconazole; ISA, isavuconazole; SDA, Sabouraud dextrose agar medium; CGB, L-canavanine-glycine-bromothymol blue; MALDI-TOF MS, matrix-assisted laser desorption ionization-time of flight mass spectrometry; ECVs, epidemiological cutoff values

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