Candida isolates causing refractory or recurrent oropharyngeal candidiasis in 11 hospitals in China

Figures & data

Table 1 Clinical characteristics of patients with refractory and recurrent oropharyngeal candidiasis and species distribution of the Candida isolates

Patient characteristic	Number (%) of isolates
	Total	C. albicans	C. glabrata complex	C. tropicalis	C. parapsilosis	Others
Age (years)
20–39	49 (8.7)	44	2	1	1	1
40–59	206 (37)	186	7	8	2	3
≥60	303 (54.3)	270	20	7	1	5
Gender
Male	134 (24)	113	10	5	2	4
Female	424 (76)	387	19	11	2	5
Total	558 (100)	500 (89.6)	29 (5.2)	16 (2.9)	4 (0.7)	9 (1.6)

Figure 1 Geographical distribution of Candida isolates causing refractory and recurrent oral candidiasis collected in this study. The two letters are the abbreviation of the hospitals that participated in this program, and the full hospital name can be found in the Acknowledgments section. The number in parentheses represents the number of isolates collected from the corresponding hospital, the percentage in parentheses represent the number of isolates from the corresponding hospital as a percentage of the total.

Table 2 Comparison of identification results of the 558 Candida isolates between those obtained from participating hospitals (initial identification) and those obtained from the central laboratory (final identification)

Species of final identification	No. of isolates	Agreement between initial and final identification
		Number (%) of isolates with agreement	Number (%) of isolates with identification errors
			Major	Misidentification (number)	Minor	Misidentification (number)
C. albicans	500	486 (97.2%)	12 (2.4%)	C. glabrata (5) C. tropicalis (7)	2 (0.4%)	Candida spp. (2)
C. glabrata	29	16 (55.2%)	12 (41.4%)	–	1 (3.4%)	–
C. glabrata sensu stricto	28	16 (57.2%)	12 (42.8%)	C. albicans (9) C. tropicalis (2) C. krusei (1)	0	–
C. nivariensis	1	0	0	–	1 (100%)	C. glabrata (1)
C. tropicalis	16	4 (25%)	12 (75%)	C. albicans (11) C. glabrata (1)	0	–
C. parapsilosis	4	1 (25%)	3 (75%)	–	0	–
C. parapsilosis sensu stricto	3	1 (33.3%)	2 (66.7%)	C. tropicalis (1) C. krusei (1)	0	–
C. orthopsilosis	1	0	1 (100%)	C. albicans (1)	0	–
C. krusei	2	2 (100%)	0	–	0	–
C. lusitaniae	2	0	1 (50%)	C. krusei (1)	1 (50%)	Candida spp. (1)
C. guilliermondii	2	0	1 (50%)	C. krusei (1)	1 (50%)	Candida spp. (1)
C. norvegensis	1	0	1 (100%)	C. albicans (1)	0	–
C. carpophila	1	0	1 (100%)	C. glabrata (1)	0	–
C. pelliculosa	1	0	1 (100%)	C. glabrata (1)	0	–
Total	558	509 (91.2%)	44 (7.9%)		5 (0.9%)

Note: *A minor error of identification of the isolate was defined as correct identification of an isolate to the genus level but inability to identify it to the species level (eg, C. albicans identified as Candida spp.) or initial correct identification of an isolate to the level but not to the species level (eg, C. metapsilosis or C. orthopsilosis identified as C. parapsilosis and C. nivariensis as C. glabrata). A major error was defined as other disagreements between the initial identification and the final identification.

Table 3 Antifungal susceptibility results of 558 isolates to eight antifungal agents

Organism and antifungal agent	Range (μg/mL)	MIC50	MIC90	%S/%WT	%R/%NWT
C. albicans (n=500)
Fluconazole	≤0.125–64	1	2	96	1.4
Voriconazole	≤0.015–4	0.03	0.125	95.8	0.4
Itraconazole	≤0.015–1	0.25	0.5	32.8	3
Miconazole	≤0.015->16	0.125	0.5	97.6	2.4
Ketoconazole	≤0.015–1	0.03	0.125	90.6	0.4
Amphotericin B	≤0.015–4	1	2	99.4	0.6
Nystatin	≤0.015–4	2	4	100	0
5-Flucytosine	≤0.064–1	0.125	0.25	99.8	0.2
C. glabrata (n=29)
Fluconazole	0.25–16	16	16	–	0
Voriconazole	0.03–0.5	0.5	0.5	72.4	27.6
Itraconazole	0.125–2	1	2	100	0
Miconazole	0.03–2	0.5	2	100	0
Ketoconazole	0.03–2	0.5	2	24.1	37.9
Amphotericin B	≤0.015–2	1	2	100	0
Nystatin	1–4	2	2	100	0
5-Flucytosine	≤0.064–0.125	≤0.064	0.125	100	0
C. tropicalis (n=16)
Fluconazole	0.25–128	0.5	64	93.8	6.2
Voriconazole	≤0.015–8	0.03	8	93.8	6.2
Itraconazole	0.125–0.5	0.25	0.5	100	0
Miconazole	≤0.015–16	0.25	8	93.8	6.2
Ketoconazole	≤0.015–0.5	0.064	0.5	87.5	0
Amphotericin B	1–2	2	2	100	0
Nystatin	0.125–2	1	2	100	0
5-Flucytosine	≤0.064	≤0.064	≤0.064	100	0
C. parapsilosis (n=4)
Fluconazole	0.5–8	1	1	75	25
Voriconazole	0.03–0.5	0.03	0.064	75	0
Itraconazole	0.25–1	0.5	0.5	75	25
Miconazole	1–2	1	1	75	25
Ketoconazole	0.03–0.25	0.064	0.064	75	0
Amphotericin B	0.5–2	1	1	100	0
Nystatin	1–2	2	2	100	0
5-Flucytosine	≤0.064–0.25	0.064	0.064	100	0
Other species (n=9)
Fluconazole	0.25–16	8	16	–	–
Voriconazole	≤0.015–0.5	0.25	0.5	–	–
Itraconazole	0.03–1	0.5	1	–	–
Miconazole	0.064–4	2	4	–	–
Ketoconazole	≤0.015–1	0.25	1	–	–
Amphotericin B	0.5–4	1	4	–	–
Nystatin	0.125–2	1	2	–	–
5-Flucytosine	≤0.064–4	0.125	2	–	–

Table 4 Review about the species distribution of yeast species obtained from OPC and IFI patients

Studies	No. of hospitals	Region	No. of isolates	C. albicans	C. glabrata	C. tropicalis	C. parapsilosis	Other species	Ref.
Invasive fungal infections
CHIF-NET	65	China	8,829	44.9	10.8	17.2	20	7.1	Xiao et al^Citation28
BJ-NET	28	China (Beijing only)	1,201	50.3	15.1	13.3	13.4	7.9	Guo et al^Citation29
ARTEMIS	133	Worldwide	19,7619	65.3	11.3	7.2	6.0	10.2	Pfaller et al^Citation30
Oropharyngeal candidiasis
OPC 1	1	Japan	154	72.8	23.4	1.9	1.3	0.6	Kamikawa et al^Citation31
OPC 2	1	UK	618	84.3	9.5	2.1	1.9	2.2	Kuriyama et al^Citation26
OPC 3	1	China (Hainan only)	313	54.3	21.7	12.5	1	10.5	Wu et al^Citation11
OPC 4	1	China (Yunnan only)	320	82.2	9.1	0.6	3.8	4.3	Li et al^Citation15
OPC 5	1	Tanzania	296	84.5	6.8	2.7	0	6	Hamza et al^Citation27
Present study	11	China	558	89.6	5.2	2.9	0.7	1.6	Yu et al

Table S1 The clinical breakpoints and epidemiological cutoff values ^(18−23) against common Candida species used in this study

	MIC CBPs			MIC ECV
	S	I/SDD	R	WT	Non-WT
FLZ
C. albicans	≤2	4	≥8
C. glabrata complex	–	≤32	≥64
C. tropicalis	≤2	4	≥8
C. parapsilosis complex	≤2	4	≥8
VOR
C. albicans	≤0.012	0.25-0.5	≥1
C. glabrata complex				≤0.25	>0.25
C. tropicalis	≤0.012	0.25-0.5	≥1
C. parapsilosis complex	≤0.012	0.25-0.5	≥1
ITR
C. albicans	≤0.12	0.25-0.5	≥1
C. glabrata complex				≤4	>4
C. tropicalis				≤0.5	>0.5
C. parapsilosis complex				≤0.5	>0.5
MCZ	≤1		≥2
KCZ	≤0.0625	0.125-0.5	≥1
AMB				≤2	>2
NYS	≤4	8-32	≥64
5-FC				≤0.5	>0.5

Table S2 The cases of 21 patients suffered mixed oropharyngeal yeast infections summarized

No. of patients	Mixed infections
11	C. albicans+C. glabrata
2	C. albicans+C. glabrata+C. tropicalis
2	C. albicans+C. tropicalis
1	C. albicans+C. parapsilosis
1	C. albicans+C. guilliermondii
1	C. albicans+C.carpophila
1	C. albicans+C. lusitaniae
1	C. albicans+C. norvegensis
1	C. guilliermondii + C. parapsilosis

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