Systematic Characterization of Epidemiology, Antifungal Susceptibility, Risk Factors and Outcomes of Candidaemia: A Six-Year Chinese Study

Figures & data

Table 1 Demographics and Clinical Characteristics of the Patients with Candidaemia

Demographics	Number of Patients (%)
Age (years old)	63 (IQR, 51–71)
Sex (male)	57 (49.6%)
ICU admission	45(39.1%)
aCCI (point)	5(IQR, 3–6)
Comorbidities
Hematological malignancy	29(25.2%)
Solid-organ cancer	26(22.6%)
Coronary heart disease	25(21.7%)
Diabetes mellitus	18(15.7%)
Risk factors
CVC	69 (60.0%)
Mechanical ventilation	58(50.4%)
Urinary catheter	55(47.8%)
TPN	50(43.5%)
Body cavity drainage tube	45(39.1%)
Prior antibiotic exposure	114 (98.2%)
Prior antifungals exposure	45(39.1%)
Prior steroids exposure	4(3.5%)
Previous surgery	47 (40.9%)
Chemotherapy	35(29.6%)
Hemodialysis	17(14.8%)
Severity of disease
Neutropenia	36(31.3%)
Septic shock	38(33.0%)

Abbreviations: ICU, intensive care unit; aCCI, age-adjusted Charlson comorbidity index; CVC, central venous catheter; TPN, total parenteral nutrition.

Figure 1 The incidence of Candida BSI from 2016 to 2021. The figure showed the change in the crude incidence of Candida BSI and the incidence rate of two major types of candidaemia through the time-course study. The crude incidence rate was calculated by the number of candidaemia cases per 1000 admissions between 2016 and 2021 in Hefei, Anhui. Overall, an increasing trend of incidence rate in candidaemia through the years was seen. Particularly, the incidence of Candida tropicalis BSI was always higher than that of Candida albicans BSI, except in 2018 and 2019.

Table 2 Azole Resistance Among Candida Isolates from 2016–2021

Species and Drugs	2016	2017	2018	2019	2020	2021	Total
	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Candida tropicalis	n=4	n=6	n=6	n=2	n=10	n=10	n=38
Fluconazole(R)	1(25.0)	1(16.7)	2(33.3)	1(50.0)	5(50.0)	5(50.0)	15(39.5)
Voriconazole(R)	1(25.0)	1(16.7)	1(16.7)	1(50.0)	3(30.0)	2(20.0)	9(23.7)
Itraconazole(R)	1(25.0)	1(16.7)	2(33.3)	1(50.0)	2(20.0)	6(60.0)	13(34.2)
Candida albicans	n =1	n =3	n =8	n =6	n =7	n =7	n =32
Fluconazole(R)	0	0	1(12.5)	0	0	0	1(3.1)
Voriconazole(R)	0	0	0	0	0	0	0
Itraconazole(R)	0	0	1(12.5)	0	0	0	1(3.1)
Candida parapsilosis	n =4	n =0	n =2	n =3	n =5	n =8	n =22
Fluconazole(R)	1(25.0)	0	0	0	0	0	1(4.5)
Voriconazole(R)	0	0	0	0	0	0	0
Itraconazole(R)	1(25.0)	0	0	0	0	0	1(4.5)
Candida glabrata	n =2	n =1	n =3	n =1	n =7	n =3	n =17
Fluconazole(R)	0	0	0	1(100)	0	0	1(5.9)
Voriconazole(R)	0	0	0	1(100)	0	0	1(5.9)
Itraconazole(R)	0	0	0	1(100)	0	0	1(5.9)
Candida krusei	n =0	n =1	n =1	n =0	n =0	n =2	n =4
Fluconazole(R)	0	1(100)	1(100)	0	0	2(100)	4(100)
Voriconazole(R)	0	0	0	0	0	0	0
Itraconazole(R)	0	0	0	0	0	0	0
Others	n =1^a	n =0	n =0	n =0	n =0	n =1^b	n =2
Fluconazole(R)	0	0	0	0	0	0	0
Voriconazole(R)	0	0	0	0	0	0	0
Itraconazole(R)	0	0	0	0	0	0	0

Notes: ^aCandida guilliermondii, ^bCandida famata. R: resistance against azole. CBPs for Candida spp. susceptibility to fluconazole and voriconazole were obtained from CLSI M60, while CBPs for susceptibility of Candida spp. against itraconazole were from EUCAST and ECV. Lacking the specific CBPs for Candida famata, we referred to the interpretation of Candida albicans for evaluation of susceptibility.

Figure 2 Trends in the species distribution of candidaemia from 2016 to 2021. The figure showed the change in the species distribution of candidaemia between 2016 and 2021. Candida tropicalis BSI always ranked at the top except in 2018 and 2019. The most prevalent species was Candida tropicalis (38/115, 33.0%), followed by Candida albicans (32/115, 27.8%), Candida parapsilosis complex (22/115, 19.1%), Candida glabrata (17/115, 14.8%), Candida krusei (4/115, 3.5%) and others Candida spp. (2/115, 1.8%). Candida non-albicans species comprised more than half of the isolates, mainly attributed to Candida tropicalis accounting for 45% of the non-albicans isolates.

Table 3 Comparison Between Candida tropicalis BSI and Candida non-tropicalis BSI

Variables [n (%)]	Candida tropicalis BSI n=38	Candida non-tropicalis BSI n=77	Univariate Analysis P-value	Multivariate Analysis Odds Ratio (95% CI)	P-value
Age (years old)	62(IQR, 43–72)	64(IQR, 52–71)	0.321
Sex (male)	18(47.4)	39(50.6)	0.741
ICU admission	7(18.4)	38(49.4)	0.002*
aCCI (point)	5(IQR, 3–7)	5(IQR, 2–6)	0.207
Hematological malignancy	22(57.9)	7(9.0)	0.000*	5.424(1.507–19.520)	0.010*
Solid-organ cancer	5(13.2)	22(28.6)	0.073
Coronary heart disease	8(21.1)	17(22.0)	0.900
Diabetes mellitus	3(7.9)	15(19.5)	0.120
CVC	27(71.1)	42(54.5)	0.092
Mechanical ventilation	12(31.6)	46(59.7)	0.005*
Urinary catheter	10(26.3)	45(58.4)	0.002*
TPN	12(31.6)	38(49.4)	0.073
Body cavity drainage tube	10(26.3)	35(45.5)	0.051
Prior antibiotic exposure	37(97.4)	77(100.0)	1.000
Prior antifungals exposure	25(65.8)	20(26.0)	0.000*
Prior steroids exposure	4(10.5)	0(0.0)	0.999
Previous surgery	7(18.4)	41(53.2)	0.001*
Chemotherapy	24(63.2)	10(13.0)	0.000*
Hemodialysis	3(7.9)	14(18.2)	0.155
Neutropenia	25(65.8)	12(15.9)	0.000*	3.800(1.160–12.453)	0.027*
Septic shock	8(21.1)	30(39.0)	0.059

Note: *Significant statistical difference (P<0.05).

Abbreviations: BSI, bloodstream infection; ICU, intensive care unit; aCCI, age-adjusted Charlson comorbidity index; CVC, central venous catheter; TPN, total parenteral nutrition; OR, odds ratio; CI, confidence interval.

Table 4 Comparison Between Candida albicans BSI and Candida non-albicans BSI

Variables [n (%)]	Candida albicans BSI n=32	Candida non-albicans BSI n=83	Univariate Analysis P-value	Multivariate Analysis Odds Ratio (95% CI)	P-value
Age (years old)	67(IQR, 56–73)	63(IQR, 49–71)	0.086
Sex (male)	18(56.3)	39(47.0)	0.374
ICU admission	16(50.0)	29(34.9)	0.141
aCCI (point)	5(IQR, 3–6)	5(IQR, 3–6)	0.898
Hematological malignancy	1(3.1)	28(33.7)	0.008*
Solid-organ cancer	13(40.6)	14(17.1)	0.009*
Coronary heart disease	6(18.8)	19(22.9)	0.630
Diabetes mellitus	7(21.9)	11(13.3)	0.259
CVC	20(62.5)	49(59.0)	0.734
Mechanical ventilation	21(65.6)	37(44.6)	0.046*
Urinary catheter	21(65.6)	34(41.0)	0.020*
TPN	14(43.8)	36(43.4)	0.971
Body cavity drainage tube	17(53.1)	28(33.7)	0.059
Prior antibiotic exposure	32(100)	82(98.8)	1.000
Prior antifungals exposure	6(18.8)	39(47.0)	0.008*
Prior steroids exposure	0(0.0)	4(4.8)	0.999
Previous surgery	24(75.0)	24(28.9)	0.000*	4.915(1.853–13.034)	0.001*
Chemotherapy	2(6.3)	33(39.7)	0.003*
Hemodialysis	2(6.3)	15(18.1)	0.127
Neutropenia	2(6.3)	35(42.2)	0.002*
Septic shock	12(37.5)	26(31.3)	0.529

Note: *Significant statistical difference (P<0.05).

Abbreviations: BSI, bloodstream infection; ICU, intensive care unit; aCCI, age-adjusted Charlson comorbidity index; CVC, central venous catheter; TPN, total parenteral nutrition; OR, odds ratio; CI, confidence interval.

Table 5 Comparison Between Candida parapsilosis BSI and Candida non-parapsilosis BSI

Variables [n (%)]	Candida parapsilosis BSI n=22	Candida non-parapsilosis BSI n=93	Univariate Analysis P-value	Multivariate Analysis Odds Ratio (95% CI)	P-value
Age (years old)	60(IQR, 48–70)	64(IQR, 53–71)	0.390
Sex (male)	10(45.5)	47(50.5)	0.668
ICU admission	13(59.1)	32(34.4)	0.037*
aCCI (point)	4(IQR, 2–6)	5(IQR, 3–6)	0.051
Hematological malignancy	3(13.6)	26(28.0)	0.175
Solid-organ cancer	3(13.6)	24(25.8)	0.235
Coronary heart disease	4(18.2)	21(22.6)	0.654
Diabetes mellitus	2(9.1)	16(17.2)	0.355
CVC	11(50.0)	58(62.4)	0.290
Mechanical ventilation	16(72.7)	42(45.2)	0.024*
Urinary catheter	12(54.5)	43(46.2)	0.484
TPN	17(77.3)	33(35.5)	0.001*	6.182(OR:2.091–18.273)	0.001*
Body cavity drainage tube	10(45.5)	35(37.6)	0.500
Prior antibiotic exposure	22(100)	92(98.9)	1.000
Prior antifungals exposure	7(31.8)	38(40.9)	0.436
Prior steroids exposure	0(0.0)	4(4.3)	0.999
Previous surgery	3(13.6)	33(35.5)	0.695
Chemotherapy	3(13.6)	32(34.4)	0.068
Hemodialysis	6(27.3)	11(11.8)	0.075
Neutropenia	3(13.6)	34(36.6)	0.049*
Septic shock	10(45.5)	28(30.1)	0.173

Note: *Significant statistical difference (P<0.05).

Abbreviations: BSI, bloodstream infection; ICU, intensive care unit; aCCI, age-adjusted Charlson comorbidity index; CVC, central venous catheter; TPN, total parenteral nutrition; OR, odds ratio; CI, confidence interval.

Table 6 Logistic Regression Analysis of Risk Factors Associated with 30-Day Crude Mortality in Patients with Candidaemia

Variables [n (%)]	Survival n=84	Death n=31	Univariate Analysis P-value	Multivariate Analysis Odds Ratio (95% CI)	P-value
Age (years old)	66(IQR:57–75)	62(IQR:51–71)	0.318
Sex (male)	41(48.8)	16(51.6)	0.790
ICU admission	29(34.5)	16(51.6)	0.098
aCCI (point)	4(IQR:2–6)	6(IQR:4–7)	0.024*	1.303(OR:1.052–1.614)	0.015*
Hematological malignancy	20(23.8)	9(29.0)	0.568
Solid-organ cancer	18(21.4)	9(29.0)	0.395
Coronary heart disease	19(22.6)	6(19.4)	0.707
Diabetes mellitus	14(16.7)	4(12.9)	0.623
CVC	48(57.1)	21(67.7)	0.305
Mechanical ventilation	39(46.4)	19(61.3)	0.160
Urinary catheter	38(45.2)	17(54.8)	0.362
TPN	33(39.3)	17(54.8)	0.138
Body cavity drainage tube	38(45.2)	7(22.6)	0.031*
Prior antibiotic exposure	84(100.0)	30(96.8)	1.000
Prior antifungals exposure	31(36.9)	14(45.2)	0.422
Prior steroids exposure	2(2.3)	2(6.5)	0.310
Previous surgery	37(44.0)	11(35.5)	0.410
Chemotherapy	22(26.2)	13(41.9)	0.107
Hemodialysis	12(14.3)	5(16.1)	0.805
Neutropenia	22(26.2)	15(48.4)	0.026*	2.642(OR:1.847–16.722)	0.002*
Septic shock	19(22.6)	19(61.3)	0.000*	8.679(OR:2.983–25.246)	0.000*

Note: *Significant statistical difference (P<0.05).

Abbreviations: ICU, intensive care unit; aCCI, age-adjusted Charlson comorbidity index; CVC, central venous catheter; TPN, total parenteral nutrition; OR, odds ratio; CI, confidence interval.