Aspergillus Species in Lower Respiratory Tract of Hospitalized Patients from Shanghai, China: Species Diversity and Emerging Azole Resistance

Figures & data

Figure 1 Distribution of Aspergillus spp. in the lower respiratory tract of hospitalized patients of different ages and sexes in Shanghai, China. (The top pie chart shows Aspergillus species distribution within each of the five 20-year age groups, 0–20; 21–40; 41–60; 61–80; and 81–100. The bottom bar graph shows the number of Aspergillus isolates from the two sexes for each of the five age groups. Aside from the 0–20 age group where only two isolates were obtained, A. fumigatus was the most common species across all age groups and that more isolates were obtained from males than females).

Figure 2 A phylogenetic tree for the representative Aspergillus spp. isolates from our study using the maximum likelihood method based on the combined sequences of ITS, BenA and CaM loci. (Type strains for all species found in our samples were included as references for confirmation of species identification. “*” means antifungal resistant isolates of Aspergillus spp. in our study; “bold font” indicates type strain for that species).

Table 1 Summary Distribution of Susceptibilities of the 98 Clinical Isolates of Aspergillus spp. to Nine Antifungal Drugs as Determined Based on the M38-3A Protocol Established by the Clinical and Laboratory Standards Institute (CLSI)

Species/Number		MIC or MEC (µg/mL) for
		AFG	CFG	MFG	ITZ	VRZ	RVZ	PSZ	ISZ	AmB
A. fumigatus complex (57)	MIC range	≤0.015–0.03	0.06–1	≤0.015–0.12	0.25–8	0.12–16	0.25–16	0.06–1	0.25–16	1–4
	MIC50	≤0.015	0.25	0.03	0.5	0.5	1	0.25	0.5	1
	MIC 90	0.03	0.25	0.12	1	0.5	2	0.25	1	2
	GM	0.021	0.221	0.034	0.615	0.443	0.765	0.187	0.711	1.245
A. flavus complex (23)	MIC range	≤0.015–0.25	0.12–0.25	≤0.015–0.25	0.12–0.5	0.5–2	1–2	0.12–1	0.5–2	1–4
	MIC50	0.03	0.12	0.06	0.25	1	1	0.25	1	2
	MIC 90	0.06	0.25	0.12	0.5	2	2	1	2	2
	GM	0.034	0.169	0.057	0.291	0.970	1.128	0.328	1.031	1.620
A. niger complex (15)	MIC range	≤0.015–0.03	0.06–0.12	0.03–0.25	0.5–16	0.5–16	0.5–16	0.25–2	0.5–16	0.5–2
	MIC50	≤0.015	0.12	0.12	1	1	2	0.5	2	1
	MIC 90	0.03	0.12	0.25	1	2	4	0.5	4	2
	GM	0.020	0.109	0.090	0.912	1.260	1.910	0.416	2.297	1.05
A. sydowii (1)	MIC range	0.06	0.03	0.03	1	2	2	1	2	2
A. terreus (1)	MIC range	≤0.015	0.12	≤0.015	0.25	2	2	0.12	1	2
A. nidulans (1)	MIC range	0.06	0.06	0.03	0.5	0.25	0.25	0.06	0.25	2

Abbreviations: AFG, anidulafungin; CFG, caspofungin; MFG, micafungin; ITZ, itraconazole; VRZ, voriconazole; RVZ, ravuconazole; PSZ, posaconazole; ISZ, isavuconazole; AmB, amphotericin B; GM, geometric means; MIC, Minimal inhibitory concentration; MEC, Minimal effective concentration; MIC₅₀, MIC/MEC at which 50% of the isolates tested were inhibited; MIC₉₀, MIC/MEC at which 90% of the isolates tested were inhibited.

Table 2 Minimal Inhibitory Concentrations of Antifungal Drug-Resistant Isolates of Aspergillus spp. in Our Study as Determined Based on the M38-3A Protocol Established by the Clinical and Laboratory Standards Institute (CLSI)

Species	Number	MIC (µg/mL) for						cyp51A
		ITZ	VRZ	RVZ	PSZ	ISZ	AmB
A. fumigatus	CMXY 13,113	8	16	16	1	16	†	TR46/Y121F/T289A
A. fumigatus	CMXY 15,837	4	†	†	†	†	†	F46Y, G89G, M172V, N248T, D255E
A. fumigatus	CMXY 28,940	†	†	†	0.5	2	†	F46Y, G89G, M172V, N248T, D255E
A. fumigatus	CMXY 25,241	†	†	†	1	†	†	#
A. fumigatus	CMXY 10,234	†	†	†	†	†	4	#
A. fumigatus	CMXY 14,287	†	†	†	†	†	4	#
A. effusus	CMXY 22,227	†	†	†	1	†	†	##
A. flavus	CMXY 22,879	†	†	†	1	2	4	##
A. effusus	CMXY 27,481	†	†	†	1	2	4	##
A. flavus	CMXY 30,197	†	†	†	1	†	†	##
A. tubingensis	CMXY 27,207	16	16	16	2	16	†	##

Notes: “†” means the MIC ≤ epidemiological cutoff values; “#” means the mutant site of cyp51A gene was not be found; “##” means the cyp51A gene were not analyzed.

Abbreviations: ITZ, itraconazole; VRZ, voriconazole; RVZ, ravuconazole; PSZ, posaconazole; ISZ, isavuconazole; AmB, amphotericin B; MIC, minimal inhibitory concentration.