Low In Vitro Antifungal Activity of Tavaborole against Yeasts and Molds from Onychomycosis

Mahdi Abastabar; Iman Haghani; Tahereh Shokohi; Mohammad Taghi Hedayati; Seyed Reza Aghili; Ali Jedi; Sulmaz Dadashi; Shafigheh Shabanzadeh; Tahereh Hosseini; Narges Aslani; Jacques F. Meis; Hamid Badali

doi:10.1128/AAC.01632-18

DOI: 10.1128/AAC.01632-18

Article Figures & Data

Tables

TABLE 1

In vitro susceptibilities of five antifungal drugs against different fungal isolates from patients with onychomycosis^a

Genus	Species (no. of isolates)	MIC parameter	MIC (µg/ml) for:
Genus	Species (no. of isolates)	MIC parameter	Tavaborole	Voriconazole	Itraconazole	Fluconazole	Terbinafine
Candida	C. parapsilosis (27)	Range	2 to >16	0.008 to >16	0.125 to >16	0.0625 to >64	4 to >4
		MIC₅₀	16	0.016	1	0.5	4
		MIC₉₀	16	0.25	2	8	4
		GM	14.49	0.06	2.46	1.71	4
	C. tropicalis (10)	Range	8 to >16	0.0625 to >0.5	1 to >8	0.25 to >64	4 to >4
		MIC₅₀	16	0.032	2	2	4
		MIC₉₀	16	0.25	4	16	4
		GM	14.49	0.06	2.46	1.71	4
	C. albicans (7)	Range	4 to >16	0.008 to >0.016	0.25 to 16	0.125 to >4	4 to >4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	C. krusei (4)	Range	8 to 16	0.0625 to 0.016	0.5 to 1	0.5 to 16	4 to >4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	C. orthopsilosis (2)	Range	16	0.016	1	0.25 to 1	4 to >4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	C. guilliermondii (1)	Range	16	0.125	4	4	>4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	C. glabrata (1)	Range	16	0.125	4	2	>4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	All Candida strains (52)	Range	2 to >16	0.008 to >16	0.125 to >16	0.0625 to >16	4 to >4
		MIC₅₀	16	0.032	1	1	4
		MIC₉₀	16	0.25	4	8	4
		GM	12.58	0.03	0.77	0.74	4
Aspergillus	A. flavus (36)	Range	0.5 to 16	0.0625 to 0.5	0.0625 to 1	16 to >64	0.032 to 8
		MIC₅₀	2	0.25	0.125	64	0.5
		MIC₉₀	4	0.5	0.25	64	4
		GM	1.8	0.21	0.13	45.25	0.59
	A. terreus (21)	Range	1 to 4	0.125 to 1	0.0625 to 0.25	64	0.032 to 8
		MIC₅₀	2	0.25	0.016	64	4
		MIC₉₀	4	1	0.125	64	8
		GM	2.4	0.33	0.03	64	1.8
	A. niger (17)	Range	0.5 to 16	0.0625 to 2	0.0625 to >16	32 to >64	0.125 to 8
		MIC₅₀	1	0.25	0.032	32	0.5
		MIC₉₀	16	0.5	1	64	4
		GM	1.92	0.25	0.2	42.25	0.81
	A. tubingensis (8)	Range	1 to 8	0.125 to 1	0.25 to 1	64	0.25 to 8
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	A. oryzae (3)	Range	1 to 8	0.0625 to 0.125	0.032 to 0.125	32 to 64	0.0625 to 1
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	A. fumigatus (2)	Range	2 to 16	0.0625 to 0.25	0.0625 to 0.5	64 to >64	4 to >4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	A. uvarum (1)	Range	0.5	0.125	0.016	>64	4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	All Aspergillus strains (88)	Range	0.5 to 16	0.0625 to 2	0.016 to >16	0.5 to >64	0.032 to >4
		MIC₅₀	2	0.25	0.125	64	1
		MIC₉₀	4	0.5	0.5	64	4
		GM	2	0.24	0.1	50.79	0.92
Dermatophytes	T. interdigitale (8)	Range	4 to 16	0.016 to 0.0625	0.0625 to 0.125	16 to 32	0.008 to 4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	T. rubrum (5)	Range	8 to 16	0.016 to >16	0.016 to >16	2 to 16	0.008 to >4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	T. tonsurans (1)	Range	8	0.032	0.032	16	0.004
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	All dermatophyte strains (14)	Range	4 to 16	0.016 to >16	0.016 to >16	2 to 32	0.004 to >4
		MIC₅₀	8	0.032	0.0625	16	0.004
		MIC₉₀	16	0.032	0.0625	32	0.008
		GM	9.28	0.02	0.03	10.24	0.007
Fusarium	F. proliferatum (8)	Range	16 to >16	1 to 4	>16	64 to >64	>4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	F. verticillioides (2)	Range	8-16	1->16	8->16	>64	0.032- >4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	F. solani (2)	Range	16 to >16	0.5 to 2	>16	>64	>4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	Fusarium sp. (2)	Range	16	2	>16	>64	>4
		MIC₅₀	ND	ND	ND	ND	ND
		MIC₉₀	ND	ND	ND	ND	ND
		GM	ND	ND	ND	ND	ND
	All Fusarium strains (14)	Range	8 to >16	0.5 to >16	8 to >16	64 to >64	0.032 to >4
		MIC₅₀	16	2	8	64	4
		MIC₉₀	16	4	8	64	4
		GM	14.67	2	8	64	4

↵^aGM, geometric mean; MIC₅₀, concentration at which 50% of the isolates were inhibited; MIC₉₀, concentration at which 90% of the isolates were inhibited; ND, not determined.

TABLE 2

In vitro susceptibilities of 5 antifungal drugs against 170 fungal isolates from different patients with onychomycosis^b

Antifungal drug	MIC (µg/ml)^a															MIC range	MIC₅₀	MIC₉₀	GM
Antifungal drug	0.004	0.008	0.016	0.031	0.063	0.125	0.25	0.5	1	2	4	8	16	32	>64	MIC range	MIC₅₀	MIC₉₀	GM
Tavaborole								5	20	45	18	19	63			0.5 to 16	4	16	4.44
Voriconazole		4	27	14	16	30	30	25	8	9	4		3			0.008 to >16	0.125	1	0.13
Itraconazole			19	10	18	23	20	20	24	7	8	2	19			0.016 to >16	0.25	2	0.2
Fluconazole					1	7	5	11	7	10	5	2	12	8	102	0.0625 to >64	4	64	3.67
Terbinafine	10	9		3	1	12	10	13	11	11	89	1				0.004 to >4	2	4	0.74

↵a Numbers in boldface are modal values.
↵b GM, geometric mean; MIC₅₀, concentration at which 50% of the isolates were inhibited; MIC₉₀, concentration at which 90% of the isolates were inhibited.