In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts

F. Sabatelli; R. Patel; P. A. Mann; C. A. Mendrick; C. C. Norris; R. Hare; D. Loebenberg; T. A. Black; P. M. McNicholas

doi:10.1128/AAC.00163-06

DOI: 10.1128/AAC.00163-06

Article Figures & Data

Tables

TABLE 1.

In vitro activities of posaconazole, itraconazole, fluconazole, voriconazole, and amphotericin B against all fungi, molds, and yeasts tested

Antifungal agent	In vitro activity against^a:
	All fungi			All molds			All yeasts
	n	MIC (μg/ml)		n	MIC (μg/ml)		n	MIC (μg/ml)
	n	50%	90%	n	50%	90%	n	50%	90%
POS	22,850	0.063	1.0	4,499	0.125	1.0	18,351	0.063	1.0
ITC	18,877	0.125	1.0	3,204	0.5	4.0	15,673	0.125	1.0
FLC	17,884	0.5	128.0	1,779	256.0	256.0	16,105	0.5	16.0
VRC	9,598	0.031	0.5	1,826	0.25	2.0	7,772	0.031	0.5
AMB	16,567	1.0	1.0	3,013	1.0	2.0	13,554	1.0	1.0

↵ a n is the number of MICs determined. 50% and 90%, MIC₅₀ and MIC₉₀, respectively.

TABLE 2.

Comparative in vitro activities of posaconazole, itraconazole, voriconazole, and amphotericin B against mold isolates

Organism	No. of MICs	MIC (μg/ml)^a
		POS		ITC		VRC		AMB
		50%	90%	50%	90%	50%	90%	50%	90%
All molds	1,702	0.25	1.0	0.5	2.0	0.25	2.0	0.5	2.0
All hyaline molds^b	1,636	0.25	1.0	0.5^c	2.0^c	0.25	1.0	0.5	2.0
All Aspergillus spp.	1,423	0.125	0.5	0.5	2.0	0.25	0.5	0.5	1.0
A. flavus	89	0.25	0.5	0.5	1.0	0.5	1.0	1.0	2.0
A. fumigatus	1,119	0.125	0.5	0.5	1.0	0.25	0.5	0.5	1.0
A. niger	101	0.25	0.5	1.0	2.0	0.5	2.0	0.125	1.0
A. terreus	22	0.25	0.25	0.5	0.5	0.25	0.5	2.0	2.0
Other Aspergillus spp.^d	92	0.125	1.0	0.5	2.0	0.25	1.0	1.0	2.0
All zygomycetes	86	0.5	4.0	1.0	32.0	16.0	128.0	0.25	2.0
Rhizopus spp.	32	1.0	8.0	4.0	32.0	16.0	128.0	1.0	2.0
Mucor spp.	18	1.0	16.0	2.0	32.0	64.0	128.0	0.25	1.0
Absidia spp.	16	0.125	0.25	0.125	0.5	16.0	128.0	0.25	0.5
Cunninghamella spp.	6	0.031-1.0	0.031-1.0	0.125-2.0	0.125-2.0	8.0-128.0	8.0-128.0	0.125-2.0	0.125-2.0
Apophysomyces spp.	5	0.031-4.0	0.031-4.0	0.031-8.0	0.031-8.0	16.0-128.0	16.0-128.0	0.031-4.0	0.031-4.0
Saksenaea spp.	4	0.016-2.0	0.016-2.0	0.016-0.125	0.016-0.125	0.5-4.0	0.5-4.0	0.063-0.5	0.063-0.5
Rhizomucor spp.	3	0.016-0.25	0.016-0.25	0.016-0.25	0.016-0.25	2.0-16.0	2.0-16.0	0.063-0.125	0.063-0.125
Cokeromyces spp.	2	0.25-4.0	0.25-4.0	0.25-8.0	0.25-8.0	16.0-64.0	16.0-64.0	0.125-0.5	0.125-0.5
All dimorphic fungi	151	0.063	0.25	0.031	0.25	ND	ND	0.25	0.5
Histoplasma spp.	53	0.019	0.25	0.019	0.063	ND	ND	0.25	0.5
Blastomyces spp.	38	0.063	0.125	0.031	2.0	ND	ND	0.125	0.5
Coccidioides spp.	25	0.125	0.25	0.125	0.25	ND	ND	0.5	0.5
Paracoccidioides spp.	13	0.063	0.125	0.016	0.063	ND	ND	0.125	0.25
Penicillium marneffei	12	0.016	0.016	0.008	0.063	ND	ND	0.5	4.0
Sporothrix spp.	10	0.5	1.0	0.25	0.5	ND	ND	0.5	1.0
All Fusarium spp.	67	16.0	32.0	16.0^e	32.0^e	16.0	32.0	8.0	32.0
F. solani	39	32.0	32.0	ND	ND	16.0	32.0	16.0	32.0
F. oxysporum	12	2.0	4.0	ND	ND	4.0	32.0	8.0	16.0
F. moniliforme	2	1.0	1.0	ND	ND	1.0	1.0	1.0-4.0	1.0-4.0
Other Fusarium spp.^f	14	16.0	16.0	ND	ND	4.0	16.0	1.0	2.0
Agents of chromoblastomycosis, mycetoma, and phaeohyphomycosis	241	0.25	16.0	1.0	64.0	ND	ND	2.0	32.0
Scedosporium prolificans	80	16.0	32.0	64.0	64.0	ND	ND	16.0	32.0
Scedosporium apiospermum	26	0.25	1.0	1.0	32.0	ND	ND	2.0	8.0
Pseudallescheria spp.	41	0.25	1.0	0.5	1.0	ND	ND	2.0	4.0
Aspergillus nidulans	20	0.063	0.25	0.25	0.5	ND	ND	1.0	2.0
Exophiala spp.	14	0.25	0.5	0.5	1.0	ND	ND	0.5	1.0
Alternaria spp.	13	0.125	0.25	0.5	1.0	ND	ND	0.5	4.0
Cladosporium spp.	11	0.063	16.0	0.125	16.0	ND	ND	1.0	4.0
Bipolaris spp.	10	0.063	0.125	0.063	0.25	ND	ND	0.25	0.25
Other^g	26	0.125	0.25	0.25	1.0	ND	ND	0.5	1.0
Other molds^h	58	0.25	0.5	0.063	1.0	0.25	0.5	0.25	2.0

↵ a 50% and 90%, MIC₅₀ and MIC₉₀, respectively. When n is <10, the MICs shown are ranges. ND, not determined.
↵ b Includes Aspergillus spp. and Fusarium spp. (MIC data for which are shown below), and other various species, including strains of Acremonium, Basidiomycetes, Bjerkandera, Coprinus, Paecilomyces, Pseudallescheria, and Schizophyllum.
↵ c Fewer isolates (n = 1,501) were tested against ITC; therefore, the values for ITC cannot be compared directly.
↵ d Includes strains of A. glaucus, A. nidulans, A. oryzae, Aspergillus spp., A. sydowii, A. ustus, and A. versicolor.
↵ e Fewer isolates (n = 23) were tested against ITC; therefore, the values for ITC cannot be compared directly.
↵ f Unspeciated Fusarium.
↵ g Includes strains of Cladophialophora, Curvularia, Exserohilum, Fonsecaea, Pithomyces, Ramichloridium, Ulocladium, and Wangiella.
↵ h Includes strains of Acremonium, Basidiomycetes, Bjerkandera, Coprinus, Paecilomyces, Pseudallescheria, Schizophyllum, and Trichophyton.

TABLE 3.

Comparative in vitro activities of posaconazole, itraconazole, and fluconazole against isolates of dermatophytes

Organism	No. of MICs	MIC (μg/ml)^a
		POS		ITC		FLC
		50%	90%	50%	90%	50%	90%
All dermatophytes	180	0.031	0.25	0.063	0.25	4.0	64.0
Trichophyton rubrum	91	0.063	0.125	0.063	0.25	2.0	32.0
T. mentagrophytes	29	0.016	0.125	0.031	0.25	8.0	64.0
T. tonsurans	23	0.031	0.25	0.031	0.063	4.0	32.0
Other Trichophyton spp.^b	5	0.063-0.5	0.063-0.5	0.031-4.0	0.031-4.0	1.0-128.0	1.0-128.0
Microsporum spp.^c	16	0.016	0.125	0.016	0.5	2.0	128.0
Epidermophyton floccosum	15	0.016	0.25	0.016	0.25	2.0	2.0
Arthroderma benhamiae	1	0.031	0.031	0.031	0.031	1.0	1.0

↵ a 50% and 90%, MIC₅₀ and MIC₉₀, respectively. When n is <10, the MICs shown are ranges.
↵ b Includes strains of T. krajdeneii, T. raubitschekii, T. soudanense, and T. terrestre.
↵ c Includes strains of M. canis, M. gypseum, and M. persicolor.

TABLE 4.

Comparative in vitro activities of posaconazole, itraconazole, fluconazole, voriconazole, and amphotericin B against isolates of Candida spp. and Cryptococcus spp.

Organism	No. of MICs	MIC (μg/ml)^a
		POS		ITC		FLC		VRC		AMB
		50%	90%	50%	90%	50%	90%	50%	90%	50%	90%
All Candida spp.	6,965	0.063	1.0	0.125	1.0	0.5	16.0	0.031	0.5	1.0^b	1.0^b
C. albicans	3,535	0.031	0.063	0.063	0.25	0.25	2.0	0.008	0.063	1.0^b	1.0^b
C. glabrata	1,218	1.0	2.0	1.0	4.0	8.0	64.0	0.25	2.0	1.0^b	1.0^b
C. parapsilosis	970	0.063	0.25	0.25	0.5	1.0	4.0	0.031	0.125	1.0	1.0
C. tropicalis	719	0.063	0.25	0.125	0.5	1.0	4.0	0.063	0.5	1.0	1.0
C. krusei	189	0.5	1.0	1.0	1.0	32.0	64.0	0.25	0.5	1.0	2.0
C. lusitaniae	84	0.063	0.25	0.25	2.0	1.0	4.0	0.031	0.063	1.0	2.0
C. guilliermondii	26	0.25	1.0	0.5	4.0	4.0	32.0	0.063	8.0	0.5	1.0
C. dubliniensis	164	0.031	0.125	0.063	0.5	0.25	32.0	0.016	0.125	0.5	1.0
Other Candida spp.^c	60	0.25	2.0	0.5	1.0	4.0	16.0	0.063	0.25	1.0	1.0
Cryptococcus spp.^d	271	0.125	0.25	0.125	0.5	4.0	8.0	0.063	0.125	1.0	1.0

↵ a 50% and 90%, MIC₅₀ and MIC₉₀, respectively.
↵ b The number of strains of C. albicans and C. glabrata tested against AMB was slightly less (for all Candida spp., n = 6,921; for C. albicans, n = 3,517; and for C. glabrata, n = 1,192).
↵ c Includes strains of C. famata, C. kefyr, C. lipolytica, C. pelliculosa, C. pseudotropicalis, C. rugosa, C. sphaerica, C. stellatoidea, and C. zeylanoides.
↵ d Includes strains of C. laurentii and C. neoformans.

TABLE 5.

Comparative in vitro activities of posaconazole, itraconazole, fluconazole, and voriconazole, against isolates of Candida spp. exhibiting resistance to itraconazole, fluconazole, and voriconazole

Isolates (resistance level)	No. of MICs^a	MIC (μg/ml)^b
		POS		ITC		FLC		VRC
		50%	90%	50%	90%	50%	90%	50%	90%
FLC resistant (MIC, >32 μg/ml)
All Candida	446	1.0	16.0	2.0	32.0	128.0	256.0	2.0	32.0
C. albicans	167	0.5	16.0	2.0	32.0	128.0	256.0	2.0	32.0
C. glabrata	149	2.0	16.0	4.0	16.0	256.0	256.0	4.0	8.0
Other Candida spp.	130	0.5	4.0	1.0	32.0	128.0	128.0	0.5	32.0
ITC resistant (MIC, >0.5 μg/ml)
All Candida	1,151	1.0	4.0	1.0	16.0	16.0	128.0	0.5	4.0
C. albicans	176	1.0	16.0	4.0	32.0	64.0	256.0	2.0	32.0
C. glabrata	719	1.0	4.0	1.0	8.0	16.0	128.0	0.5	4.0
Other Candida spp.	256	0.5	2.0	1.0	8.0	32.0	128.0	0.5	16.0
VRC resistant (MIC, >2 μg/ml)
All Candida	234	4.0	16.0	8.0	32.0	128.0	256.0	8.0	32.0
C. albicans	101	2.0	16.0	8.0	32.0	128.0	256.0	8.0	32.0
C. glabrata	88	4.0	16.0	16.0	32.0	128.0	256.0	4.0	16.0
Other Candida spp.	45	2.0	32.0	2.0	32.0	128.0	128.0	32.0	32.0
With POS MIC of >2 μg/ml
All Candida	176	8.0	32.0	16.0	32.0	128.0	256.0	4.0	32.0
C. albicans	62	8.0	32.0	16.0	32.0	128.0	256.0	16.0	64.0
C. glabrata	86	8.0	16.0	16.0	32.0	128.0	256.0	4.0	8.0
Other Candida spp.	28	16.0	32.0	8.0	32.0	128.0	128.0	32.0	32.0

↵ a The data set is the same as that used in Table 4. There were a total of 6,595 MICs for all four drugs.
↵ b 50% and 90%, MIC₅₀ and MIC₉₀, respectively.