Triazole phenotypes and genotypic characterization of clinical Aspergillus fumigatus isolates in China

Figures & data

Table 1 MIC/MEC ranges, modal of MICs/MECs, distribution of MICs/MECs (mg/L) obtained by testing the susceptibility of 159 A. fumigatus isolates to 10 antifungal agents and the percentage of non-WT isolates for the 159 isolates of A. fumigatus

Antifungal agent	MIC/MEC range	No. of isolates with MIC/MEC of												% of non-WT isolates
Triazoles		0.008	0.016	0.031	0.063	0.125	0.25	0.5	1	2	4	8	16
Itraconazole	0.063–>16				1		9	93	49				7	4.40
Voriconazole	0.063–2				1	17	103	24	13	1				0.63
Posaconazole	0.031–1			4	63	72	11	4	5					3.14
Isavuconazole	0.063–4				1	2	5	56	88	2	4			3.77
Ravuconazole	0.063–8				3	20	112	15	2	3	2	1		3.77
Echinocandins
Micafungin	≤0.008–0.5	19	61	58	19	1		1						0
Anidulafungin	≤0.008–0.063	5	52	64	38									0
Caspofungin	0.125–0.5					10	119	30						0
Polyenes
Amphotericin B	0.5–2							5	119	35				0
Allylamines
Terbinafine	0.25–4						1	1	12	79	66			Unknown

Abbreviations: minimum inhibitory concentration, MIC; minimum effective concentration, MEC; values in bold indicate modal or most frequent MICs, Modal MIC/MEC; wild type WT. MICs are shown for amphotericin B, itraconazole, posaconazole, voriconazole, ravuconazole, isavuconazole; MECs are shown for micafungin, caspofungin and anidulafungin.

Table 2 Comparisons of activities of eight antifungal drugs tested against A. fumigatus isolates in four geographic areas

Antifungal agents	Geometric mean (MIC90/MEC90) (mg/L) for isolates from:
	East (n=37)	South-east (n=39)	North (n=61)	West (n=22)
Itraconazole	0.894 (16)^#	0.752 (1)	0.658 (1)^#	0.485 (1)*
Voriconazole	0.290 (0.5)	0.273 (1)	0.296 (0.5)	0.302 (0.5)
Posaconazole	0.116 (0.5)	0.113 (0.25)	0.091 (0.125)^#	0.137(0.25)*
Ravuconazole	0.290 (2)^#	0.264 (0.25)^#	0.228 (0.25)^#	0.401 (0.5)*
Isavuconazole	0.894 (2)^#	0.915 (1)^#	0.672 (1)*	0.624 (1)
Micafungin	0.029 (0.063)^#	0.023 (0.063)^#	0.022 (0.031)^#	0.014 (0.015)*
Anidulafungin	0.030 (0.063)^#	0.035 (0.063)^#	0.028 (0.063)^#	0.016 (0.015)*
Caspofungin	0.319 (0.5)^#	0.264 (0.25)^#	0.287 (0.5)^#	0.194 (0.25)*

Abbreviations: minimum effective concentration, MEC; minimum inhibitory concentration, MIC. Note: The one with * means that it had statistical difference (P<0.01) when compared with the one with #.

Table 3 MICs/MECs of seven triazole-resistant A. fumigatus isolates and their corresponding mutation type in the cyp51A gene region and geographical origin

Isolates	MICs/MECs (mg/L)										Mutation type in cyp51A gene	Geographical origin
	Amb	Itr	Vor	Pos	Isa	Rav	Anid	Mic	Cas	Ter
STJ0048	1	>16	1	1	4	2	0.015	0.03	0.25	2	TR34/L98H	South-eastern area
STJ0049	1	>16	1	1	4	2	0.03	≤0.008	0.25	2	TR34/L98H	South-eastern area
STJ0105	1	>16	1	1	4	2	0.06	0.03	0.25	2	—	Eastern area
STJ0107	1	>16	0.5	1	2	4	0.03	0.03	0.5	2	TR34/L98H/S297T	Eastern area
STJ0119	0.5	>16	0.125	0.5	1	0.125	0.03	0.03	0.5	1	G54V	Eastern area
STJ0140	0.5	>16	0.5	1	2	8	0.06	0.06	0.5	2	TR34/L98H/S297T	Eastern area
XJ138	1	16	2	0.5	4	4	0.015	0.015	0.125	2	TR34/L98H	Western area

Abbreviations: amphotericin B, Amb; anidulafungin, Anid; caspofungin, Cas; isavoconazole, Isa; itraconazole, Itr; minimum effective concentration, MEC; micafungin, Mic; minimum inhibitory concentration, MIC; posaconazole, Pos; ravuconazole, Rav; terbinafine, Ter; voriconazole, Vor.

Figure 1 Genotypic analysis of triazole-resistant Aspergillus fumigatus clinical isolates, including seven triazole-resistant isolates in this study, and analyses published previously from China and other countries. The dendrogram is based on a categorical analysis of nine microsatellite markers in combination with the unweighted Pair Group Method with arithmetic mean clustering. The scale bar indicates the percentage identity. *Denotes the seven clinical Chinese isolates in this study.