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School of Molecular & Biomedical Science
THE UNIVERSITY OF ADELAIDE
AUSTRALIA 5005

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Dr David Ellis

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Antifungal Susceptibility Profiles

Antifungal susceptibility profiles for common human pathogenic fungi.

Susceptibility based on at least 75% of clinical isolates being susceptible. Due to the marked influence of methodology on MIC values for different antifungals and lack of correlation between in vitro and in vivo results, the results of in-vitro studies should be interpreted with caution. This table is based on current treatment regimes and in vitro susceptibility data from both the literature and the WCH Mycology Unit. Currently, the most reliable data is for fluconazole and itraconazole against Candida infections; the least reliable data is for the moulds.

S = Susceptible; SDD = Susceptible but Dose Dependent; R = Resistant; V = Variable; I = Intermediate; N = No data.

Susceptible - Dose Dependent is a new category recently described by the NCCLS subcommittee on antifungal susceptibility testing for isolates where susceptibility is dependent on achieving the maximal possible blood level of the antifungal agent. For fluconazole doses of 400 mg/day or more may be required for adults with normal renal function and habitus. For itraconazole plasma concentration of >0.5 ug/ml may be required for optimal response. [see Rex et al. CID 1997; 24:235-247].

AmB = Amphotericin B; Flu = Fluconazole; Vori = Voriconazole; Itra = Itraconazole; Keto = Ketoconazole; Terb = Terbinafine [* topical only]; 5FC = 5-Fluorocytosine; Griseo =Griseoflvin.

Yeasts

Organism	AmB	Flu	Vori	Itra	Keto	Terb	5FC	Caspo
Candida albicans	S 0.5 ug/ml	S 0.5-1 ug/ml	S 0.06 ug/ml	S 0.25 ug/ml	S 0.25 ug/ml	V 0.03->128 ug/ml	S 1.0 ug/ml	S
Candida famata	S 0.5 ug/ml	SDD 4-8 ug/ml	S 0.06 ug/ml	S 0.25 ug/ml	S 0.25 ug/ml	N	S 1.0 ug/ml	S
Candida glabrata	S 0.5 ug/ml	SDD 2-32 ug/ml	S 1-2 ug/ml	SDD 0.5-1 ug/ml	V 1-4 ug/ml	R >128 ug/ml	S 0.5 ug/ml	S
Candida guilliermondii	S 0.5 ug/ml	SDD 4-8 ug/ml	S 0.25-0.5 ug/ml	S 0.5 ug/ml	S 0.5-1 ug/ml	V 6.25-100 ug/ml	S 0.125-0.2 ug/ml	S
Candida kefyr	S 0.5 ug/ml	S 0.5-1 ug/ml	S 0.03 ug/ml	S 0.25-0.5 ug/ml	S 0.25 ug/ml	R 0.5-50 ug/ml	V 0.03-16 ug/ml	S
Candida krusei	S 0.5-1 ug/ml	R 32-64 ug/ml	S 0.5-1 ug/ml	SDD 0.5 ug/ml	I 1.0 ug/ml	R 50->100 ug/ml	V 8-32 ug/ml	S
Candida lusitaniae	V 0.5-2 ug/ml	S 0.5-1 ug/ml	S 0.06 ug/ml	S 0.25 ug/ml	S 0.25 ug/ml	N	S 0.125 ug/ml	S
Candida parapsilosis	S 0.5-1 ug/ml	S 1-2 ug/ml	S 0.06 ug/ml	S 0.125-0.5 ug/ml	S 0.5 ug/ml	S 0.25-2 ug/ml	S 1.0 ug/ml	S
Candida tropicalis	S 0.5 ug/ml	SDD 1-8 ug/ml	S 0.25 ug/ml	S 0.25 ug/ml	V 0.5-1 ug/ml	V 10-128 ug/ml	S 1.0 ug/ml	S
*Cryptococcus neoformans*	S 0.5-1 ug/ml	SDD 2-8 ug/ml	S 0.25 ug/ml	SDD 0.5 ug/ml	S 0.25 ug/ml	S 0.25 ug/ml	S 2-8 ug/ml	R
Malassezia furfur	S	S	S	S	S	S*	S	N
*Saccharomyces cerevisiae*	S 0.5 ug/ml	S 2-8 ug/ml	S 0.03 ug/ml	S 0.5-1 ug/ml	S 0.5 ug/ml	N	S 0.125 ug/ml	N
Trichosporon beigellii	S 1.0 ug/ml	S 2-8 ug/ml	S 0.125 ug/ml	S 0.125 ug/ml	S 0.5 ug/ml	V 0.05-128 ug/ml	I 8-16 ug/ml	N

Dermatophytes

Organism	Terb	Flu	Itra	Keto	Griseo	Vori
Trichophyton sp.	S	S	S	S	S	S
Epidermophyton floccosum	S	S	S	S	S	S
Microsporum sp.	S	S	S	S	S	S

Moulds

Organism	AmB	Flu	Vori	Itra	Keto	Terb	5FC	Caspo
Aspergillus fumigatus	S 1.0 ug/ml	R >100 ug/ml	S 0.5 ug/ml	SDD 0.5 ug/ml	R 8 .0 ug/ml	S 0.5 ug/ml	R >64 ug/ml	S
Aspergillus flavus	S 1-2 ug/ml	R >100 ug/ml	S 0.5-1 ug/ml	SDD 0.5-1 ug/ml	R 8.0 ug/ml	S 0.5 ug/ml	R > 64 ug/ml	S
Pseudallescheria boydii [=Scedosporium apiospermun].	V 1-16 ug/ml	V 8-64 ug/ml	S 0.5 ug/ml	V 0.5-4 ug/ml	V 1-4 ug/ml	R 10-100 ug/ml	R > 64 ug/ml	N
Scedosporium prolificans	R >16 ug/ml	R > 64 ug/ml	S 0.5-1 ug/ml	R > 8 ug/ml	R >16 ug/ml	R >100 ug/ml	R >64 ug/ml	N
*Fusarium sp*	I 1-4 ug/ml	R > 64 ug/ml	S 1-4 ug/ml	R > 8 ug/ml	R > 16 ug/ml	R 0.5-128 ug/ml	R >64 ug/ml	N
*Bipolaris sp*	S 0.25 ug/ml	R > 64 ug/ml	S 0.25-0.5 ug/ml	S 0.5 ug/ml	S 0.5 ug/ml	S 0.5-1 ug/ml	R > 64 ug/ml	N
*Cladophialophora sp*	S 1.0 ug/ml	V 4-64 ug/ml	S 1.0 ug/ml	S 0.125 ug/ml	V	S 0.25-1 ug/ml	S 0.25 ug/ml	N
*Exophiala sp*	S 0.25 ug/ml	R 64 ug/ml	S 0.25 ug/ml	S 0.5 ug/ml	V 0.5-2 ug/ml	S 0.06-2 ug/ml	V 4-64 ug/ml	N
*Phialophora sp*	S 0.5-1 ug/ml	R 16-64 ug/ml	S 0.25 ug/ml	S 0.5 ug/ml	V 0.5 ug/ml	S 1.0 ug/ml	N	N
*Paecilomyces sp*	V 0.5- 16 ug/ml	R 64 ug/ml	S 0.5-1 ug/ml	V 0.5- 8 ug/ml	N	V 1-64 ug/ml	V 0.5-64 ug/ml	N
*Penicillium sp*	S 0.5-1 ug/ml	V 4-64 ug/ml	S 0.5 ug/ml	S 0.5 ug/ml	S 1.0 ug/ml	S 0.5-4 ug/ml	V 0.5 ug/ml	N

Dimorphic moulds

Organism	AmB	Flu	Vori	Itra	Keto	Terb	5FC	Caspo
Histoplasma capsulatum	S 0.25 ug/ml	SDD 8-32 ug/ml	S 0.25 ug/ml	S 0.25 ug/ml	S 0.25-0.5 ug/ml	S 0.25 ug/ml	V 0.125->64 ug/ml	N
Coccidioides immitis	S 0.5 ug/ml	SDD 8-32 ug/ml	S 0.125 ug/ml	S 0.5-1 ug/ml	S 0.5-1 ug/ml	S 0.5 ug/ml	R > 64 ug/ml	N
Sporothrix schenckii	S 1-2 ug/ml	R > 64 ug/ml	S 4-8 ug/ml	S 0.5-1 ug/ml	S 0.5 ug/ml	S 0.5-2 ug/ml	V 2-> 64 ug/ml	N

Zygomycetes

Organism	AmB	Flu	Vori	Itra	Keto	Terb	5FC	Caspo
Absidia, Apophysomyces, Mucor, Rhizomucor, Rhizopus, Saksenaea	S 0.25-2 ug/ml	R > 64 ug/ml	R 2-32 ug/ml	R 2-8 ug/ml	R 4-16 ug/ml	R 1->100 ug/ml	R > 64 ug/ml	N

Breakpoints [Rex et al. CID 1997; 24:235-47].

Amphotericin B MIC

Susceptible < 1 ug/ml
Intermediate 2 ug/ml
Resistant > 4 ug/ml

Comments: MIC's for Candida species tightly cluster at 0.25-1.0 ug/ml. The detection of resistance using the NCCLS M27A susceptibility test method for Amphotericin B may be unreliable on RPMI media. An MIC of > 1 ug/ml is likely to be resistant. Antibiotic Medium 3 may enhance the detection of resistance, but this medium is not standardised and substancial lot-to-lot variability is possible.

Fluconazole MIC

Susceptible < 8 ug/ml
Susceptible Dose dependent 16-32 ug/ml
Resistant > 64 ug/ml

Itraconazole MIC

Susceptible < 0.125 ug/ml
Susceptible Dose dependent 0.25-0.5 ug/ml
Resistant > 1 ug/ml

5 Fluorocytosine MIC

Susceptible < 4 ug/ml
Intermediate 8-16 ug/ml
Resistant >32 ug/ml

Comments: Breakpoints based on historical data and drug pharmacokinetics.