Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?

Table 1 Baseline cohort characteristics between liver intensive care unit patients with fungal and bacterial infections

Characteristic	Bacteria, n = 1831	Fungal, n = 271	P value2
Age	60 (50, 66)	58 (46, 66)	0.3
Sex
Female	73 (40)	12 (44)
Male	110 (60)	15 (56)
Race
American Indian/Alaska Native	1 (0.5)	0 (0)
Asian	1 (0.5)	0 (0)
Black	27 (15)	6 (22)
Declined	1 (0.5)	2 (7.4)
Multiracial/cultural	7 (3.8)	1 (3.7)
Unavailable	7 (3.8)	1 (3.7)
White	139 (76)	17 (63)
Charlson Comorbidity Score	6.00 (5.00, 7.00)	6.00 (4.00, 7.00)	0.3
Hepatocellular carcinoma	18 (9.8)	1 (3.7)	0.5
Principal liver diagnosis
Acute liver failure	10 (5)	2 (7.4)	> 0.9
Cirrhosis	141 (78)	21 (78)	> 0.9
Alcohol-associated hepatitis (comorbid3)	16 (9.3)	6 (22)	0.093
Acute severe liver injury/other4	34 (17)	4 (14.6)	> 0.9
Etiology of viral disease
Viral hepatitis	24 (13)	9 (33)	0.016
Alcohol-associated	75 (41)	13 (48)	0.6
Autoimmune	8 (4.4)	1 (3.7)	> 0.9
NASH	44 (24)	5 (19)	0.7
Primary biliary cholangitis	4 (2.2)	1 (3.7)	> 0.9
Primary sclerosing cholangitis	17 (9.3)	1 (3.7)	0.5
Other	34 (19)	6 (22)	0.9
Toxins	4 (2.2)	0 (0)	> 0.9
Ischemic injury	5 (2.7)	1 (3.7)	> 0.9
Cryptogenic	16 (8.7)	1 (3.7)	0.6
Decompensation defining events
Ascites	144 (79)	23 (85)	0.6
Hepatic encephalopathy	138 (75)	25 (93)	0.08
Hepatorenal syndrome	63 (34)	16 (59)	0.023
EV history/variceal bleeding	106 (58)	16 (59)	> 0.9
HPS	2 (1.1)	0 (0)	> 0.9
PoPHTN	6 (3.3)	0 (0)	0.7
Hepatic hydrothorax	27 (15)	3 (11)	0.8
SBP	45 (25)	12 (44)	0.053
Coagulopathy	122 (67)	21 (78)	0.3
Thrombocytopenia	107 (58)	20 (74)	0.2

¹Median (IQR); n (%).

²Welch Two Sample t-test; Standardized Mean Difference; Two sample test for equality of proportions.

³Only 1 case of alcohol-associated hepatitis occurred without comorbid cirrhosis in bacterial cohort, not included in proportion shown.

⁴Other etiologies include chronic post-transplant patients with liver injury/recurrent portal hypertension, portal vein thrombosis, non-hepatitis viral infection and Caroli disease in conjunction with severe liver injury.

HPS: Hepatopulmonary syndrome; PoPTHN: Portopulmonary hypertension; SBP: Spontaneous bacterial peritonitis.

Table 2 Epidemiology of Candida isolates among patients with fungal patients in the intensive care unit

Organism	Urinary source	Bacteremia	Spontaneous peritonitis	Secondary peritonitis	Tracheitis	Total per organism
Candida glabrata	-	6	2	1	-	9
Candida albicans	1	4	2	-	1	8
Candida krusei	-	2	-	-	-	2
Candida dubliniensis	1	3	2	-	-	6
Candida (other)	2	2	-	-	-	4
Total per source	4	17	6	1	1

Table 3 Transplant and intensive care outcomes comparison between fungal and bacterial cohorts

Characteristic	Bacteria, n = 1831	Fungal, n = 271	P value2
Intensive care outcomes
ACLF grade			0.017
< 2	50 (36)	2 (9.5)
≥ 2	90 (64)	19 (90)
Death during admission or hospice	95 (52)	25 (93)	< 0.001
Vasopressor requirement	129 (70)	26 (96)	0.004
Mechanical ventilation	118 (65)	26 (96)	< 0.001
Indication for intubation
Airway protection	93 (79)	22 (85)	0.6
Respiratory failure	25 (21)	4 (15)
Dialysis due to acute kidney injury	95 (52)	21 (78)	0.014
ICU LOS (d)	5 (2, 10)	6 (4, 16)	0.063
Hospital LOS (d)	16 (7, 28)	17 (12, 30)	0.3
Hosp admit to ICU (d)	0 (0, 6)	8 (0, 13)	0.046
Transplant-related outcomes
Evaluated for transplant	107 (58)	13 (48)	0.3
Listed	57 (53)	4 (31)	0.13
Organ listed			0.3
Liver	44 (79)	3 (60)
Liver and kidney	12 (21)	2 (40)
Hold placed	32 (57)	4 (100)	0.14
Transplant occurred	28 (50)	0 (0)	0.056

¹n (%); Range; Median (IQR).

²Pearson's Chi-squared test; Wilcoxon rank sum test; Fisher's exact test.

ACLF: Acute on chronic liver failure; ICU: Intensive care unit; LOS: Length of stay.

Table 4 Comparison of infection characteristics among liver patients in intensive care unit between fungal and bacterial cohorts

Characteristic	Bacteria, n = 1831	Fungal, n = 271	P value2
MDRO	90 (50)	10 (37)	0.2
MELD-Na (time of positive culture)	28 (22, 33)	33 (25, 38)	0.017
Child-Pugh score (time of positive culture)	11.00 (9.00, 12.00)	11.00 (10.00, 13.00)	0.064
CLIF-C score (time of positive culture)	11.00 (9.00, 13.00)	13.00 (12.00, 14.50)	< 0.001
Lab values of interest at time of culture
Leukocyte count	13 (7, 19)	16 (11, 18)	> 0.9
C-reactive protein	6 (3, 12)	5 (4, 8)	0.057
Albumin	2.70 (2.20, 3.30)	3.10 (2.70, 3.40)	0.086
Bilirubin	6 (2, 13)	13 (4, 23)	0.035
Lactate	2.9 (1.9, 5.2)	4.4 (2.2, 7.3)	0.3
International normalized ratio	1.80 (1.40, 2.10)	2.05 (1.78, 3.00)	0.046

¹n (%); Median (IQR).

²Pearson's Chi-squared test; Wilcoxon rank sum test; Fisher's exact test; Welch Two Sample test.

MDRO: Multi-drug resistant organism; MELD-Na: Model for End Stage Liver Disease-Sodium; CLIF: Chronic liver failure consortium organ failure score.

Table 5 Comparison of pre-infection variables between liver patients in intensive care unit with fungal and bacterial cohorts

Characteristic	Bacteria, n = 1831	Fungal, n = 271	P value2
APACHE III Score	91 (71, 112)	108 (96, 121)	0.003
Acute Physiology Score	65 (50, 90)	86 (75, 108)	0.003
MELD-Na (admission)	29 (23, 35)	32 (28, 38)	0.041
Stress dose steroid use in past 3 months	29 (16)	6 (22)	0.4
Foley in past 48 h	80 (44)	5 (19)	0.013
Central line in past 48 h	73 (40)	14 (52)	0.2
Positive MRSA nasal swab	15 (8.2)	5 (19)	0.15
Prior MDRO infection/colonization	39 (21)	11 (41)	0.027
Regular LVP	72 (39)	14 (52)	0.2
Immunosuppressive medications (at time of admission)	40 (22)	6 (22)	> 0.9
Charlson Comorbidity Score	6.00 (5.00, 7.00)	6.00 (4.00, 7.00)	0.5
Prior antibiotic classes exposed	4.00 (3.00, 5.00)	4.00 (3.00, 5.00)	0.9
Prior antifungal classes exposed			0.11
0	104 (57)	10 (37)
1	58 (32)	14 (52)
2	16 (8.8)	2 (7.4)
3	3 (1.7)	1 (3.7)
COVID within 30 d prior	9 (4.9)	2 (7.4)	0.6

¹n (%); Median (IQR).

²Pearson's Chi-squared test; Wilcoxon rank sum test; Fisher's exact test.

MRSA: Methicillin-resistant Staphylococcus aureus; MDRO: Multi-drug resistant organism; LVP: Large-volume paracentesis; MELD-Na: Model for End Stage Liver Disease-Sodium; APACHE: Acute Physiology and Chronic Health Evaluation.