Antifungal Susceptibility Tests and the cyp51 Mutant Strains among Clinical Aspergillus fumigatus Isolates from Korean Multicenters

Figures & data

Table 1. Amino acid substitutions in cyp51A, cyp51B and in vitro antifungal susceptibility testing results for 84 A. fumigatus clinical isolates in Korea.

Category	Minimum inhibitory concentration (μg/mL)				Amino acid substitutions in cyp51 genes		No. (%) of isolates
	Itraconazole	Voriconazole	Posaconazole	Amphotericin B	cyp51A	cyp51B
Azole-resistant isolates (N = 2)
	2	0.25–1	0.25	0.5–1	None	None	2 (2.4)
Azole-susceptible isolates (N = 82)
	0.5	0.25–0.5	0.25–0.5	0.5	F46Y/M172V/E427K	None	2 (2.4)
	0.5	0.5	0.5	2	F46Y/M172V/N248T/D255E/E427K	Q42L	1 (1.2)
	0.5	0.5	0.25	0.5	F46Y/N248T/D255E/E427K	None	1 (1.2)
	0.5	0.25–1	0.06–0.5	0.5	N248K	None	2 (2.4)
	0.5	0.5	0.125	0.5	M39I	None	1 (1.2)
	0.5	0.25	0.125	0.5	D343N	None	1 (1.2)
	1	0.25	0.25	0.5	G408V	None	1 (1.2)
	0.25–1	0.25–0.5	0.125–0.25	0.25–4	None	Q42L	10 (11.9)
	0.25–1	0.25–1	0.06–0.5	0.125–4	None	None	63 (75.0)
Total	0.25-2	0.25–1	0.06–0.5	0.125–4			84 (100.0)

Table 2. Clinical information of the patients with Aspergillus fumigatus isolates harboring amino acid substitutions in cyp51A or cyp51B.

A. fumigatus isolate								Patient
No	AAS in Cyp51A	AAS in Cyp51B	Year	Source	Hos	Age (yr)	Sex (M/F)	Underlying diseases	Previous antifungals use	Post-antifungal therapy	Outcome
Strains associated with probable invasive aspergillosis^a
1	G408V	None	2012	Sputum	A	46	F	AML	ITR, FLU, CAS	AMB, VOR	Dead
2	M39I	None	2012	Bronchial wash	A	62	M	AML	N/A	AMB, VOR	Dead
3	N248K	None	2012	Sputum	A	37	F	Bronchiolitis obliterans	FLU	AMB, VOR	Survive
4	None	Q42L	2012	Sputum	A	48	M	HL, Peripheral T cell lymphoma	FLU	ITR, AMB	Dead
5	None	Q42L	2013	Pus	B	77	F	IPF, DM, HTN	AMB	AMB	Dead
6	None	Q42L	2012	Sputum	A	66	M	HL	N/A	FLU	Dead
Strains associated with colonization
7	D343N	None	2012	Sputum	A	70	M	IPF, Pulmonary HTN	N/A	No	Dead
8	F46Y,N248T, D255E,E427K	None	2012	Sputum	A	69	M	Salmonella sepsis	N/A	No	Survive
9	F46Y,M172V,E427K	None	2013	Urine	C	75	F	HTN	No	No	Survive
10	F46Y,M172V,E427K	None	2013	Sputum	D	41	M	TB	No	No	Survive
11	N248K	None	2012	Bronchial wash	A	53	M	TB	N/A	No	Survive
12	F46Y,M172V, N248T,D255E, E427K	Q42L	2013	Sputum	C	59	M	DM, CKD	No	No	Survive
13	None	Q42L	2012	Sputum	A	46	F	Liver cirrhosis, bacterial peritonitis	N/A	AMB	Dead
14	None	Q42L	2012	Sputum	A	62	M	NSCLC, Glottic cancer	N/A	No	Survive

^aProbable invasive aspergillosis was classified according to criteria from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) [20].

AAS: amino acid substitution; AML: acute myeloid leukemia; CAS: caspofungin; CKD: chronic kidney disease; DM: diabetes mellitus; FLU: fluconazole; HL: Hodgkin’s lymphoma; Hos: hospital; HTN: hypertension; IPF: idiopathic pulmonary fibrosis; ITR: itraconazole; N/A: not available; NSCLC: non-small cell lung cancer; TB: tuberculosis.

De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–1821.

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