Evaluation of candidemia risk factors and Candida species distribution in intensive care units among patients with and without COVID-19

Cemile Uyar; Emel Yıldız; Özlem Genç; Öznur Ak; Emel Koçak; Sevil Alkan; Canan Balcı; Pınar Korkmaz; Duru Mıstanoğlu Özatağ; Halil Aslan

doi:10.15537/smj.2024.45.6.20240102

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Table 1

- Comparisons of the demographic and clinical data between coronavirus disease-19 positive and coronavirus disease-19 negative patients.

Variables	COVID-19 (+)	COVID-19 (-)	P-values	χ²	df
Gender
Female	34 (47.9)	20 (47.6)	0.978	0.001	1
Male	37 (52.1)	22 (52.4)	0.978	0.001	1
Age (years), mean±SD	71±15	68±17	0.402
Number of days of hospitalization, median (IQR)	29 (20-40)	46 (28-85)	0.0002^*
Concomitant Gram positive infection
Yes	15 (21.1)	6 (14.3)	0.366	0.82	1
No	56 (78.9)	36 (85.7)	0.366	0.82	1
Concomitant Gram negative infection
Yes	36 (50.7)	25 (59.5)	0.363	0.83	1
No	35 (49.3)	17 (40.5)	0.363	0.83	1
Other cultures
Blood	29 (59.6)	22 (71.0)	0.636	1.71	3
Urine	3 (5.9)	1 (3.2)
Tracheal aspirate	16 (31.4)	7 (22.6)
The others	3 (5.9)	1 (3.2)
APACHE 2 score, mean±SD	18.5±8.5	21.7±11.8	0.101
Expected mortality (%), median (IQR)	25.0 (12.0-55.0)	31.4 (20.3-67.1)	0.074
Comorbidity
Yes	59 (83.1)	29 (69.0)	0.082	3.02	1
No	12 (16.9)	13 (31.0)	0.082	3.02	1
Intubation
Yes	54 (76.1)	40 (95.2)	0.008^*	6.94	1
No	17 (23.9)	2 (4.8)	0.008^*	6.94	1
Intubation day after hospitalization, median (IQR)	3 (1-10)	2 (1-6)	0.655
CVC
Yes	57 (80.3)	41 (97.6)	0.009^*	6.89	1
No	14 (19.7)	1 (2.4)	0.009^*	6.89	1
Parenteral nutrition
Yes	53 (74.6)	41 (97.6)	0.002^*	9.96	1
No	18 (25.4)	1 (2.4)	0.002^*	9.96	1
Steroid
Yes	62 (87.3)	12 (28.6)	<0.0001^*	40.30	1
No	9 (12.7)	30 (71.4)	<0.0001^*	40.30	1
Antibiotics
Yes	63 (88.7)	41 (97.6)	0.092	2.84	1
No	8 (11.3)	1 (2.4)	0.092	2.84	1
Lymphopenia
Yes	42 (59.2)	19 (45.2)	0.151	2.06	1
No	29 (40.8)	23 (54.8)	0.151	2.06	1

↵Values are presented as numbers and percentages (%), mean ± standard deviation (SD), or median and interquartile range (IQRs). The comparisons of numerical variables between groups were analyzed with the independent-sample t-test and the Mann-Whitney-U test according to the distribution of data. The comparisons of categorical variables between groups were analyzed with the Chi-square (χ²) test.
↵* A p-value of < 0.05 was considered significant.
COVID-19: coronavirus disease-19, CVC: central venous catheterization, APACHE: acute physiology and chronic health evaluation, χ²: Ki-kare, df: degree of freedom

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Table 2

- Distribution of Candida species isolated from coronavirus disease-19 positive and coronavirus disease-19 negative patients.

Candida species	COVID-19 (+)	COVID-19 (-)	P-value	χ²	df
C. parapsilosis	14 (19.7)	25 (59.5)	0.0001^*	29.87	7
C. glabrata	5 (7.0)	4 (9.5)
C. albicans	38 (53.5)	4 (9.5)
C. tropicalis	4 (5.6)	5 (11.9)
C. spp	7 (9.9)	1 (2.4)
C. kefyr	1(1.4)	1 (2.4)
C. krusei	1 (1.4)	1 (2.4)
C. lusitaniae	1 (1.4)	1 (2.4)
Total	71 (100)	42 (100)

Values are presented as numbers and percentages (%). The comparisons of categorical variables between groups were analyzed with the Chi-square (χ²) test.
↵* A p-value of <0.05 was considered significant.
COVID-19: coronavirus disease-19, χ²: Ki-kare, df: degree of freedom, C.: Candida

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Table 3

- Distribution of susceptible antifungals in coronavirus disease-19 positive and coronavirus disease-19 negative patients.

Antifungal	COVID-19 (+)	COVID-19 (-)	P-value	χ²	df
Anidulafungin	70 (98.5)	41 (97.6)	0.164	6.51	4
Caspofungin	68 (95.7)	41 (97.6)
Vorikonazol	60 (84.5)	23 (54.7)
Micafungin	69 (97.1)	41 (97.6)
Flukonazol	50 (70.4)	15 (35.7)

Values are presented as numbers and percentages (%). COVID-19: coronavirus disease-19, χ²: Ki-kare, df: degree of freedom

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Table 4

- Distribution of antifungal susceptibilities of Candida species isolated from coronavirus disease-19 positive (group 1) and coronavirus disease-19 negative (group 2) patients.

Candida species	Anidulafungin		Caspofungin		Vorikonazol		Micafungin		Flukonazol
Candida species	Group 1	Group 2	Group 1	Group 2	Group 1	Group 2	Group 1	Group 2	Group 1- Group 2
C. parapsilosis	13 (18.6)	25 (61)	12 (17.6)	25 (61)	10 (16.7)	14 (60.9)	13 (18.8)	25 (61)	2 (4.0) - 4 (22.2)
C. glabrata	5 (7.1)	4 (9.8)	5 (7.4)	4 (9.8)	3 (5)	2 (8.7)	5 (7.2)	4 (9.8)	3 (6.0) - 3 (16.6)
C. albicans	38 (54.3)	4 (9.8)	37 (54.4)	4 (9.8)	35 (58.3)	4 (17.4)	37 (53.6)	4 (9.8)	35 (70.0) - 4 (22.2)
C. tropicalis	4 (5.7)	4 (9.8)	4 (5.9)	4 (9.8)	2 (3.3)	2 (8.7)	4 (5.8)	4 (9.8)	4 (8.0) - 3 (16.6)
C. spp	7 (10)	1 (2.4)	7 (10.3)	1 (2.4)	7 (11.7)	0 (0.0)	7 (10.1)	1 (2.4)	6 (12.0) - 2 (11.1)
C. kefyr	1 (1.4)	1 (2.4)	1 (1.5)	1 (2.4)	1 (1.7)	0 (0.0)	1 (1.4)	1 (2.4)	0 (1.0) - 1(5.5)
C. krusei	1 (1.4)	1 (2.4)	1 (1.5)	1 (2.4)	1 (1.7)	1 (4.3)	1 (1.4)	1 (2.4)	0 (1.0) - 1(5.5)
C. lusitaniae	1 (1.4)	1 (2.4)	1 (1.5)	1 (2.4)	1 (1.7)	0 (0.0)	1 (1.4)	1 (2.4)	0 (0.0) - 0(0.0)
Total	70 (100)	41 (100)	68 (100)	41 (100)	60 (100)	23 (100)	69 (100)	41 (100)	50 (100) - 18 (100)

Values are presented as numbers and percentages (%). P-value of 0.600, χ²=25.51, df=28. The comparisons of categorical variables between groups were analyzed with the Chi-square (χ²) test (a p-value of <0.05 was considered significant).
C.: Candida, χ²: Ki-kare, df: degree of freedom

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Table 5

- Distribution of Gram (+) and Gram (-) bacterial species accompanying Candida infection isolated from coronavirus disease-19 positive and coronavirus disease-19 negative patients.

Gram bacteria species	COVID-19 (+)	COVID-19 (-)	P-value	χ²	df
Gram (+) bacteria species
Coagulase-negative Staphylococci	5 (33.3)	4 (66.6)	0.024*	16.10	7
Enterococcus faecium	8 (53.3)	0 (0.0)
Enterococcus spp	2 (13.3)	2 (33.3)
Total	15 (100)	6 (100)
Gram (-) bacteria species
Acinetobacter spp	13 (36.1)	7 (28)	0.131	11.18	7
Klebsiella spp	15 (41.7)	10 (40)
Escherichia coli	2 (5.6)	0 (0.0)
Pseudomonas spp	2 (5.6)	6 (24)
Stenotrophomonas maltophilia	1 (2.8)	0 (0.0)
Proteus spp	0 (0.0)	2 (8)
Klebsiella spp + Pseudomonas	1 (2.8)	0 (0.0)
Klebsiella spp + Acinetobacter	2 (5.6)	0 (0.0)
Total	36 (100)	25 (100)

Values are presented as numbers and percentages (%). The comparisons of categorical variables between groups were analyzed with the Chi-square (χ²) test. A p-value of <0.05 was considered significant.
COVID-19: coronavirus disease-19, χ²: Ki-kare, df: degree of freedom

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Table 6

- Comparisons of the laboratory data between coronavirus disease-19 positive and coronavirus disease-19 negative patients.

Variables	Group 1	Group 2	P-values
WBC (10/uL)	14.16 (7.92-17.89)	8.45 (6.09-17.28)	0.03^*
HGB (g/dL)	9.6 (8.6-11.7)	8.7 (8.0-9.4)	0.0003^*
PLT (10/uL)	168.000 (86.000-277.000	153.000 (94.750-449.000)	0.593
Procalcitonin (ng/mL)	1.49 (0.46-4.58)	2.21 (0.79-5.32)	0.206
CRP (mg/L), mean±SD	155.2±79.2	163.5±99.2	0.625
Creatinine (mg/dL)	0.97 (0.70-1.83)	0.90 (0.69-1.90)	0.816
AST (U/L)	30 (28-79)	30.5 (18-64.5)	0.04^*
ALT (U/L)	32 (28-72)	16 (10.3-53.3)	0.0002^*

WBC: white blood cell, HGB: hemoglobin, PLT: platelet, CRP: C-reactive protein, AST: aspartate aminotransferase, ALT: alanine aminotransferase, Group 1: coronavirus disease positive, Group 2: coronavirus disease negative

↵Normally distributed data are presented as mean ± standard deviation (SD) and not normally distributed data were expressed as median and interquartile range (IQRs). The comparisons of data between groups were analyzed with the independent-sample t-test and the Mann-Whitney-U test according to the distribution of data.
↵* A p-value of <0.05 was considered significant.

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Appendix 1

- Clinical and Laboratory Standards Institute M27.

Antifungal agents	Susceptible	Susceptible dose dependent	Intermediate	Resistant
Fluconazole^*	≤8	16-32		≥64
Itraconzole	≤0.125	0.25-0.5		≥1
Flucytosine	≤4		8-16	≥32
Caspofungin	≤2^*^†
Voriconazole	<1			>4

↵* Candida krusei recovered from super infections have not been found to be susceptible to fluconazole and may require alternative antifungal therapy.
^† In clinical studies, voriconazole MIC₉₀ for C. glabrata baseline was 4 ug/ml; 13/50 (26%). C. glabrata baseline isolates were resistant (MIC ≥4ug/ml) to voriconazole. However, based on 1054 isolates tested in surveillance studies the MIC₉₀ was 1 ug/ml.

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Appendix 2

- Minimum inhibitory concentration interpretative criteria for Candida species as per Clinical and Laboratory Standards Institute M27.

Antifungal agents	Susceptible	Susceptible dose dependent	Intermediate	Resistant	Non-susceptible
Anidulafungin	≤2				>2
Caspofungin	≤2				>2
Fluconazole*	≤8	16-32		≥64
5-Flucytosine	≤4		8-16	≥32
Itraconzole	≤0.125	0.25-0.5		≥1
Micafungin	≤2				>2
Voriconazole	≤1	2		≥4