Chapters
Part III: Guidelines for selected antimicrobial use
3.10 Antifungal agents
- The mechanism of action for the major antifungal classes is summarised in Table 3.2.
- It is important to note that there are significant within and between class variations in the antifungal spectrum of the agents (Table 3.3). They also differ in their pharmacokinetic properties and dosage adjustment in renal and hepatic dysfunction (Table 3.4).
- Echinocandins are not active or show very limited activity against Cryptococcus neoformans, Trichosporon beigelii, dematiaceous moulds, Zygomycetes, Fusarium spp. and dimorphic fungi (Blastomyces, Histoplasma, Coccidioides) because these fungi do not have the target for the echinocandins to act.
- Fluconazole shows activity against Candida albicans. It is also active against non-albicans Candida but MICs are higher, especially for C. glabrata.
- Analysis of fungaemia data in local hospitals showed that about 10% of the isolates were potentially resistant to fluconazole and the echinocandins (Figure 3.1).
- Table 3.5 showed a suggested scheme for choosing antifungals.
- Table 3.6 summarised the antifungal agents that have been evaluated in randomised controlled trials for their five major indications. In general, the different agents were non-inferior to each other for the major outcomes. In several studies, superior results were demonstrated for certain outcomes.
Table 3.2 Mechanisms of antifungal action
Table 3.3 General patterns of antifungal susceptibility
S, susceptible; S-DD, susceptibility is dose-dependent; I, intermediate; R, resistant
Amphotericin B (AMB); 5-flucytosine (5FC); fluconazole (FLU); itraconazole (ITR); posaconazole (POS); voriconazole (VOR); caspofungin (CAS); anidulafungin (AFG); micafungin (MFG)
Note:
1 Sporadic cases of breakthrough C. glabrata and C. parapsilosis infection have been reported in the literature Reference: (169–179).
Table 3.4 Comparison of selected pharmacokinetic parameters for the azoles and caspofungin
Table 3.5 A suggested scheme for systemic antifungal agents
Table 3.6 Selected clinical trials conducted on licensed antifungals
Note:
AML, acute myelogenous leukaemia
HSCT, haematopoietic stem cell transplantation
MDS, myelodysplastic syndromes
Agent with superior results for some outcomes is underlined.
Figure 3.1 Distribution by species for 595 episodes of fungaemia in HA, 2015-20161
Note:
- 1Each species from each patient is only counted once.
- 2Including one each of Candida doobushaemulonii, Candida guilliermondii, Candida haemulonii, Candida novegensis, Cryptococcus spp., Fusarium solani and Malassezia furfur.