Molecular epidemiology and antifungal susceptibilities of Aspergillus species isolated from patients with invasive aspergillosis

Sarigüzel, Fatma Mutlu; Koç, Ayse Nedret; Sağiroğlu, Pınar; Atalay, Mustafa Altay; Borlu, Arda; Canöz, Özlem; Dinç, Bedia

doi:10.1590/1806-9282.20220441

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Original Article • Rev. Assoc. Med. Bras. 69 (1) • 2023 • https://doi.org/10.1590/1806-9282.20220441 copy

Molecular epidemiology and antifungal susceptibilities of Aspergillus species isolated from patients with invasive aspergillosis

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

The aim of this study was to evaluate the demographic data, molecular epidemiology, and in vitro antifungal susceptibility results of patients with Aspergillus isolated from various clinical specimens.

METHODS:

A total of 44 Aspergillus strains were studied. The definition of invasive aspergillosis in patients was made according to 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) criteria. Strains were phenotypically and molecularly identified. Demographic characteristics of patients and genotypes of strains were evaluated. Phylogenetic analysis was done by the The Unweighted Pair-Group Method with Arithmetic Mean (UPGMA). Antifungal susceptibility of strains was determined according to The Clinical and Laboratory Standards Institute (CLSI)-M61-Ed2 and The European Committee on Antimicrobial Susceptibility Testing (EUCAST).

RESULTS:

A total of 11 patients were classified as proven and 33 as probable invasive aspergillosis. There was a statistically significant difference in age groups, subdisease, neutropenic, and receiving chemotherapy between groups. A total of 23 strains were identified as Aspergillus fumigatus, 12 as Aspergillus niger, 6 as Aspergillus flavus, and 3 as Aspergillus terreus. Phylogenetic analysis revealed five different genotypes. No statistical difference was found in the comparisons between patients groups and genotype groups. There was a statistically significant difference between genotype groups and voriconazole, posaconazole, and itraconazole Minimum Inhibition Concentration (MIC).

CONCLUSION:

Accurate identification of strains and antifungal susceptibility studies should be performed due to azole and amphotericin B resistance. Genotyping studies are important in infection control due to identifying sources of infection and transmission routes.

KEYWORDS:
Aspergillus; Microbial sensitivity tests; Molecular epidemiology; Sequence analysis

		Proven IA (n=11)	Probable IA (n=33)	Control group (n=19)	χ²	p-value
		n (%)	n (%)	n (%)	χ²	p-value
Gender^* * Line percentage.
	Men	8 (17.8)	24 (53.3)	13 (28.9)	0.121	0.941
	Women	3 (16.7)	9 (50.0)	6 (33.3)	0.121	0.941
Age (years)^* * Line percentage.
	<18	0 (0.0)	2 (66.7)	1 (33.1)	13.033	0.043
	18–45	2 (10.5)	6 (31.6)	11 (57.9)
	46–64	5 (18.5)	16 (59.3)	(22.2)
	>65	4 (28.6)	9 (64.3)	1 (7.1)
Neutropenia^* * Line percentage.
	Yes	7 (26.9)	16 (61.5)	3 (11.5)	8.069	0.018
	No	4 (10.8)	17(45.9)	16 (43.2))	8.069	0.018
Intravenous catheter^* * Line percentage.
	Yes	9 (25.7)	17 (48.6)	9 (25.7)	3.807	0.149
	No	2 (18.2)	16 (57.1)	10 (35.7)	3.807	0.149
Chemotherapy^* * Line percentage.
	Yes	10 (25.0)	16 (40.0)	14 (35.0)	7.625	0.022
	No	1 (4.3)	17 (73.9)	5 (21.7)	7.625	0.022
Prophylactic antifungal^* * Line percentage.
	Yes	7 (31.8)	10 (45.5)	5 (22.7)	4.920	0.085
	No	4 (9.8)	23 (56.1)	14 (34.1)	4.920	0.085
Mortality^* * Line percentage.
	Yes	4 (26.7)	5 (33.3)	6 (40.0)	2.952	0.229
	No	7 (14.6)	28 (58.3)	13 (27.1)	2.952	0.229
Subdisease (n=63)^* * Line percentage.
	Hematological cancers	7 (41.2)	3 (17.6)	7 (41.2)	31.978	0.000
	Other cancers	4 (22.2)	10 (55.6)	4 (22.2)
	COPD	0 (0.0)	6 (85.7)	1 (14.3)
	DM	0 (0.0)	7 (100.0)	0 (0.0)
	RA	0 (0.0)	7 (100.0)	0 (0.0)
	Others	0 (0.0)	3 (30.0)	7 (70.0)
Strains^ Column percentage. Bold indicate statistically significant p-values. Hematological cancers: acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia. Other cancers: lung, bone, nasal, skin, kidney, breast, and stomach cancers. COPD: chronic obstructive pulmonary disease; DM: diabetes mellitus; RA: rheumatological disease.
	A. fumigatus	4 (36.4)	19 (57.5)	0	6.821	0.078
	A. niger	2 (18.1)	10 (30.3)	0
	A. flavus	4 (36.4)	2 (6.1)	0
	A. terreus	1 (9.1)	2 (6.1)	0
Genotypes^ Column percentage. Bold indicate statistically significant p-values. Hematological cancers: acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia. Other cancers: lung, bone, nasal, skin, kidney, breast, and stomach cancers. COPD: chronic obstructive pulmonary disease; DM: diabetes mellitus; RA: rheumatological disease.
	A1	4 (36.4)	16 (48.6)	0	8.214	0.223
	A2	0	3 (9.1)	0
	B	1 (9.1)	2 (6.1)	0
	C	3 (27.4)	1 (3.0)	0
	D	0	1 (9.1)	0
	E1	1 (9.1)	1 (3.0)	0
	E2	0	2 (6.1)	0

		MIC (μg/mL)			Antifungal susceptibility, n (%)
		Ranges	MIC₅₀	MIC₉₀	WT	S	R
A. fumigatus (n: 23)
	AMB	0.016–1.5	0.125	0.50	22	22	1
	VOR	0.064–0.25	0.125	0.125	23	23	–
	POS	0.002–0.25	0.032	0.125	23	23	–
	ANI	0.002–0.032	0.002	0.032	ND	ND	ND
	ITR	0.125–1	1	1	23	23	–
	CAS	0.016–0.25	0.032	0.125	ND	ND	ND
A. niger (n: 12)
	AMB	0.125–0.5	0.125	0.25	12	12	–
	VOR	0.036–0.25	0.125	0.25	12	ND	ND
	POS	0.002–0.25	0.064	0.125	12	ND	ND
	ANI	0.002–0.02	0.002	0.008	ND	ND	ND
	ITR	0.125–1	1	1	12	ND	ND
	CAS	0.002–0.25	0.008	0.016	ND	ND	ND
A. flavus (n: 6)
	AMB	0.25–0.5	0.5	0.5	6	ND	ND
	VOR	0.064–0.5	0.125	0.125	6	ND	ND
	POS	0.032–0.25	0.125	0.125	6	ND	ND
	ANI	0.002–0.004	0.002	0.004	ND	ND	ND
	ITR	0.25–1	0.25	0.5	6	6	–
	CAS	0.008–0.064	0.016	0.016	ND	ND	ND
A. terreus (n:3)^* * MIK50 and MIK90 not calculated due to low number of A. terreus strains. ND: not done; WT: wild type; S: susceptible; R: resistant; AMB: amphotericin B; VOR: voriconazole; POS: posaconazole; ANI: anidulafungin; ITR: itraconazole; CAS: caspofungin.
	AMB	0.002–0.50			3	ND	ND
	VOR	0.064–0.125			3	ND	ND
	POS	0.016–0.02			3	3	–
	ANI	0.002–0.02			ND	ND	ND
	ITR	0.25–0.25			3	3	–
	CAS	0.032–0.125			ND	ND	ND

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[1] *Corresponding author: fmutluguzel@gmail.com