Part III: Guidelines for Selected Antimicrobial Use

3.16 Antifungal Drugs

The taxonomy of pathogenic yeasts is undergoing changes, with several antifungal-resistant yeast species being reclassified into different genera. [310–312] To avoid confusion among clinicians, this document maintains the familiar genus Candida for these organisms. Figure 3.1 illustrates the distribution of fungal species associated with fungaemia in the Hospital Authority from 2019 to 2023.
Table 3.1 provides a summary of the mechanisms of action for the major antifungal classes. The antifungal spectrum varies significantly within and among classes of antifungal agents, along with different pharmacokinetic properties necessitating dosage adjustments for patients with kidney or liver impairment.
Fluconazole demonstrates activity against Candida albicans and some non-albicans Candida. However, certain strains, particularly C. glabrata, may exhibit higher MICs or resistance. C. krusei is considered intrinsically resistant to fluconazole. [313]
Echinocandins lacks activity or demonstrated limited activity against Cryptococcus neoformans, dematiaceous moulds, Fusarium species, Trichosporon species, Zygomycetes, and dimorphic fungi (Blastomyces, Coccidioides, Histoplasma) because these fungi do not have the target necessary for echinocandins to exert their effects.
Invasive candidiasis

To treat non-neutropenic adults with candidaemia, an echinocandin is the preferred initial antifungal while fluconazole is an acceptable alternative when they are not critically ill and who are considered unlikely to have a fluconazole-resistant Candida species. [313–315]

To treat neutropenic adults with candidaemia, an echinocandin is the preferred initial antifungal while lipid formulation amphotericin B is an effective but less attractive alternative due to toxicity concerns. [313–315]

Invasive aspergillosis

For invasive pulmonary aspergillosis, voriconazole is the preferred first-line treatment. [316–318]

For invasive aspergillosis in solid-organ transplant recipients, voriconazole is the preferred choice, while isavuconazole or lipid formulation amphotericin B as alternative agents. [319]

Please consult a clinical microbiologist or infectious disease physician for invasive fungal infections.

Figure 3.1: Species Distribution of Fungaemia Patients in the Hospital Authority (2019–2023)

Table 3.1: Summary of the Mechanisms of Selected Antifungals and Their General Spectrum of Activity

Organism1,2	Triazoles	Echinocandins	Amphotericin B	5-flucytosine
Mechanism of action	Inhibit fungal ergosterol synthesis	Inhibit fungal 1,3-beta-D-glucan synthase	Damages fungal cell membrane by binding to ergosterol	Inhibits fungal RNA and DNA synthesis
Yeasts
Candida albicans	Susceptible	Susceptible	Susceptible	Susceptible
Candida auris	Variable	Variable	Variable	Variable
Candida glabrata	Variable	Susceptible	Susceptible	Susceptible
Candida krusei	Variable	Susceptible	Susceptible	Resistant
Candida parapsilosis	Susceptible	Variable	Susceptible	Susceptible
Candida tropicalis	Susceptible	Susceptible	Susceptible	Susceptible
Cryptococcus neoformans	Susceptible	Resistant	Susceptible	Susceptible
Trichosporon species	Variable	Resistant	Variable	Resistant
Mould
Aspergillus fumigatus	Variable	Susceptible	Susceptible	Resistant
Fusarium species	Variable	Resistant	Variable	Resistant
Scedosporium species	Variable	Resistant	Resistant	Resistant
Mucorales	Variable	Resistant	Susceptible	Resistant
Dimorphic fungus
Talaromyces marneffei	Variable	Resistant	Susceptible	Resistant

Footnotes:

1. The following fungi have been assigned new names: Candida auris as Candidozyma auris, Candida glabrata as Nakaseomyces glabratus, Candida krusei as Pichia kudriavzevii, Candida lusitaniae as Clavispora lusitaniae, Penicillium marneffei as Talaromyces marneffei. Tests routinely used in clinical laboratories may not be able to differentiate among members of the Candida albicans complex (C. albicans, Candida dubliniensis, and Candida africana), Candida parapsilosis complex (Candida parapsilosis, Candida metapsilosis, and Candida orthopsilosis).

2. The information provided serves as a general reference based on selected published articles in the literature. [135,314,320–333] Readers should keep in mind that antifungal resistance patterns can vary significantly within a group or genus of fungal pathogens, as well as across different geographical regions and clinical settings. Antifungal resistance can also emerge or evolve over time, making it essential to stay updated on current trends. When available, please refer to the antifungal susceptibility testing results. Beware that breakpoints may not be available for certain organisms. In the event of uncertainty, please consult a clinical microbiologist and infectious disease physician.