Clinical impact of multidrug-resistant organisms in liver cirrhosis: A retrospective cohort study in the intensive care setting

Table 1 Baseline clinical and laboratory characteristics of intensive care unit patients with cirrhosis, stratified by multidrug-resistant organism colonization and decompensation phenotype (acute decompensation vs acute-on-chronic liver failure), n (%)/median (interquartile range)

Characteristics	Total (n = 107)	Without MDRO colonization (n = 75)	With MDRO colonization (n = 32)	P value1	AD (n = 20)	ACLF (n = 87)	P value1
Clinical and laboratory data
Age (years), median	60.0 (53.0, 67.0)	59 (53.0, 66.0)	61.0 (52.5, 69.0)	0.343	56.0 (50.3, 63.0)	61.0 (53.0, 68.0)	0.118
Gender				0.123			0.475
Male	74 (69.2)	48 (64.0)	26 (81.2)		12 (60.0)	62 (71.3)
Female	33 (30.8)	27 (36.0)	6 (18.8)		8 (40.0)	25 (28.7)
Hospital admission within last 3 months	40 (37.4)	25 (33.3)	15 (46.9)	0.268	7 (35.0)	33 (37.9)	1
ICU admission within last 3 months	12 (11.2)	7 (9.3)	5 (15.6)	0.542	4 (20.0)	8 (9.2)	0.231
Systemic antibiotics within last 3 months	38 (35.5)	23 (30.7)	15 (46.9)	0.167	5 (25.0)	33 (37.9)	0.406
Long-term norfloxacin prophylaxis	3 (2.8)	3 (4.0)	0 (0)	0.553	1 (5.0)	2 (2.3)	0.466
NSBB	41 (38.3)	27 (36.0)	14 (43.8)	0.591	9 (45.0)	32 (36.8)	0.67
IPP prior to hospital	58 (54.2)	39 (52.0)	19 (59.4)	0.659	12 (60.0)	46 (52.9)	0.774
IPP prior to ICU	76 (71.0)	50 (66.7)	26 (81.2)	0.197	15 (75.0)	61 (70.1)	0.872
TIPSS	8 (7.5)	5 (6.7)	3 (9.4)	0.694	1 (5.0)	7 (8.0)	1
WBC (× 109/L)	12.2 (7.8, 16.8)	12.4 (7.2, 17.8)	11.6 (9.2, 14.3)	0.498	9.8 (5.1, 12.1)	12.7 (8.3, 17.2)	0.034
Platelets (× 109/L)	88.0 (57.5, 122.0)	100.0 (64.0, 132.0)	76.5 (45.0, 100.0)	0.004	101.0 (76.3, 138.0)	84.0 (55.5, 118.5)	0.166
Serum creatinine (μmol/L)	150.0 (84.0, 278.5)	150.0 (88.0, 305.5)	140.5 (79.8, 220.0)	0.586	67.5 (59.5, 100.5)	185.0 (101.0, 317.0)	0.094
Serum sodium (mmol/L)	134.0 (130.0, 138.0)	134.0 (130.5, 138.0)	135.0 (129.0, 138.0)	0.751	136.5 (129.8, 142.8)	134.0 (130.0, 137.5)	0.246
Serum albumin (g/L)	26.0 (22.7, 29.5)	26.0 (22.4, 29.3)	26.0 (23.3, 30.0)	0.935	27.5 (22.0, 31.3)	26.0 (23.0, 29.0)	0.584
Serum bilirubin (μmol/L)	102.0 (45.0, 219.0)	100.0 (47.6, 207.0)	139.5 (42.5, 213.0)	0.586	69.5 (37.5, 94.3)	114.0 (49.0, 280.5)	0.094
INR	1.7 (1.4, 2.2)	1.6 (1.3, 2.2)	1.77 (1.6, 2.4)	0.156	1.4 (1.3, 1.5)	1.8 (1.5, 2.4)	0
CRP (mg/L)	36.1 (17.0, 73.5)	32.4 (15.4, 75.1)	36.6 (21.3, 68.9)	0.617	37.5 (13.0, 55.1)	35.0 (17.4, 80.5)	0.29
PCT (ng/mL)	1.1 (0.5, 2.8)	1.1 (0.5, 2.8)	1.2 (0.6, 2.2)	0.824	0.5 (0.1, 1.1)	1.3 (0.6, 2.9)	0.003
AST (U/L)	97.0 (49.0, 214.0)	110.0 (49.0, 262.0)	79.5 (50.0, 133.8)	0.187	76.0 (42.8, 130.8)	106.0 (52.0, 228.0)	0.303
ALT (U/L)	48.0 (21.0, 117.5)	60.0 (22.0, 141.0)	29.5 (18.3, 79.5)	0.039	39.5 (22.0, 101.5)	49.0 (20.50, 117.50)	0.851
GGT (U/L)	67.0 (34.0, 162.5)	80.0 (39.0, 225.0)	47.5 (24.0, 87.8)	0.011	141.5 (51.8, 564.5)	60.0 (30.5, 119.5)	0.01
ALP (U/L)	108.0 (87.0, 154.5)	109.0 (86.5, 179.5)	106.0 (90.8, 129.0)	0.492	100.0 (82.5, 187.3)	109.0 (87.0, 144.5)	0.876
Cirrhosis etiology
ALD	88 (82.2)	64 (85.3)	24 (75.0)	0.315	16 (80.0)	72 (82.8)	0.752
Chronic viral hepatitis	11 (10.3)	9 (12.0)	2 (6.2)	0.5	1 (5.0)	10 (11.5)	0.685
MASLD	6 (5.6)	3 (4.0)	3 (9.4)	0.361	2 (10.0)	4 (4.6)	0.312
PSC/PBC	1 (0.9)	1 (1.3)	0 (0)	1	1 (5.0)	0 (0)	0.187
AIH	1 (0.9)	1 (1.3)	0 (0)	1	1 (5.0)	0 (0)	0.187
Cryptogenic	8 (7.5)	5 (6.7)	3 (9.4)	0.694	0 (0)	8 (9.2)	0.347
HCC	3 (2.8)	1 (1.3)	2 (6.2)	0.212	1 (5.0)	2 (2.3)	0.466
Comorbidities
Diabetes mellitus	25 (23.4)	13 (17.3)	12 (37.5)	0.045	5 (25.0)	20 (23.0)	1
Cardiovascular diseases	50 (46.7)	33 (44.0)	17 (53.1)	0.513	7 (35.0)	43 (49.4)	0.359
Respiratory diseases	15 (14.0)	9 (12.0)	6 (18.8)	0.537	2 (10.0)	13 (14.9)	0.732
Chronic kidney diseases	13 (12.1)	8 (10.7)	5 (15.6)	0.692	2 (10.0)	11 (12.6)	1
Chronic hemodialysis	1 (0.9)	1 (1.3)	0 (0)	1	0 (0)	1 (1.1)	1
Disease severity at admission
MELD score	12.0 (10.0, 13.0)	11.0 (10.0, 13.0)	12.0 (10.8, 13.3)	0.365	10.0 (8.0, 11.0)	12.0 (10.5, 13.0)	0
MELD-Na score	27.4 (21.3, 33.5)	27.0 (21.4, 34.0)	29.08 (20.9, 32.6)	0.979	19.7 (16.0, 23.3)	29.3 (24.2, 35.2)	0
SOFA score	8.0 (6.0, 11.0)	8.0 (6.0, 10.0)	8.5 (7.0, 11.0)	0.247	5.5 (4.0, 7.0)	9.0 (7.0, 11.0)	0
CLIF ACLF score	61.0 (53.8, 66.0)	61.0 (56.0, 65.8)	58.0 (53.3, 65.8)	0.558	71.0 (71.0, 71.0)	61.0 (53.5, 65.5)	0.168
Type of ICU admission
Organ failure	48 (44.9)	36 (48.0)	12 (37.5)	0.431	9 (45.0)	39 (44.8)	1
Bleeding	11 (10.3)	9 (12.0)	2 (6.2)	0.5	5 (25.0)	6 (6.9)	0.046
Infection	35 (32.7)	18 (24.0)	17 (53.1)	0.007	2 (10.0)	33 (37.9)	0.017
Other	13 (12.1)	12 (16.0)	1 (3.1)	0.103	4 (20.0)	9 (10.3)	0.259
ACLF at ICU admission	87 (81.3)	57 (76.0)	30 (93.8)	0.033	0 (0.0)	87 (100.0)	0
Organ support at admission	63 (58.9)	44 (58.7)	19 (59.4)	1	7 (35.0)	56 (64.4)	0.031
Mechanical ventilation	45 (42.1)	30 (40.0)	15 (46.9)	0.656	7 (35.0)	38 (43.7)	0.647
Vasopressors	45 (42.1)	32 (42.7)	13 (40.6)	1	0 (0.0)	45 (51.7)	0
Outcomes
Mechanical ventilation	57 (53.3)	38 (50.7)	19 (59.4)	0.539	9 (45)	48 (55.2)	0.566
Acute RRT	36 (33.6)	23 (30.7)	13 (40.6)	0.438	1 (5)	35 (40.2)	0.003
Vasopressors	52 (48.6)	34 (45.3)	18 (56.2)	0.41	1 (5)	51 (58.6)	0
28-day transplant free survival	49 (45.8)	37 (49.3)	12 (37.5)	0.361	15 (75)	34 (39.1)	0.008
Overall ICU survival	55 (51.4)	41 (54.7)	14 (43.8)	0.41	17 (85)	38 (43.7)	0.001
Overall hospital survival	45 (42.1)	35 (46.7)	10 (31.2)	0.206	15 (75)	30 (34.5)	0.002
ICU LOS	8.0 (4.0, 16.0)	8.0 (4.0, 14.0)	10.0 (3.0, 18.3)	0.513	5.0 (3.0, 10.5)	9.0 (5.0, 17.0)	0.084
Hospital LOS	22.0 (12.0, 36.0)	21.0 (12.0, 31.0)	27.0 (17.8, 47.0)	0.083	20.5 (11.8, 37.0)	24.0 (12.0, 36.0)	0.946

¹P values were calculated using Fisher’s exact or Mann-Whitney U test, as appropriate.

ICU: Intensive care unit; NSBB: Non-selective beta-blockers; IPP: Infection prevention protocol; TIPSS: Transjugular intrahepatic portosystemic shunt; WBC: White blood cell count; INR: International normalized ratio; CRP: C-reactive protein; PCT: Procalcitonin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; ALD: Alcohol-associated liver disease; MASLD: Metabolic dysfunction-associated steatotic liver disease; PSC: Primary sclerosing cholangitis; PBC: Primary biliary cholangitis; AIH: Autoimmune hepatitis; HCC: Hepatocellular carcinoma; MELD: Model for End-Stage Liver Disease; SOFA: Sequential Organ Failure Assessment; CLIF: Chronic liver failure; ACLF: Acute-on-chronic liver failure; RRT: Renal replacement therapy; LOS: Length of stay; AD: Acute decompensation; MDRO: Multidrug-resistant organism.

Table 2 Multidrug-resistant organism species identified in colonization and infection episodes at intensive care unit admission, n (%)

MDRO species	Total (n)	Colonized	Infected	P value1
MDR A. baumanii	29	8 (21.1)	21 (37.5)	0.142
Escherichia coli, ESBL	2	0 (0.0)	2 (3.6)	0.513
Escherichia coli, ESBL and OXA-48	1	0 (0.0)	1 (1.8)	1
Klebsiella oxytoca, OXA-48	1	1 (2.6)	0 (0.0)	0.404
Klebsiella pneumoniae, ESBL	3	1 (2.6)	2 (3.6)	1
Klebsiella pneumoniae, ESBL and OXA-48	5	3 (7.9)	2 (3.6)	0.391
Klebsiella pneumoniae, KPC	3	1 (2.6)	2 (3.6)	1
Klebsiella pneumoniae, OXA-48	19	8 (21.1)	11 (19.6)	0.925
MDR Pseudomonas spp.	2	2 (5.3)	0 (0.0)	0.161
VRE	10	4 (10.5)	6 (10.7)	1
MRSA	19	10 (26.3)	9 (16.1)	0.341

¹P values were calculated using Fisher’s exact test.

MDRO: Multidrug-resistant organism; A. baumanii: Acinetobacter baumannii; ESBL: Extended-spectrum beta-lactamase; OXA-48: Oxacillinase-48; KPC: Klebsiella pneumoniae carbapenemase; MDR: Multidrug-resistant; VRE: Vancomycin-resistant Enterococcus spp.; MRSA: Methicillin-resistant Staphylococcus aureus.

Table 3 Clinical outcomes stratified by multidrug-resistant organism colonization and infection status, n (%)/median (interquartile range)

Outcome	Colonized patients (n = 32)	Non-colonized (n = 75)	P value1	Infected patients (n = 91)	Non-infected (n = 16)	P value1
Mechanical ventilation	19 (59.4)	38 (50.7)	0.539	54 (59.3)	3 (18.8)	0.005a
Renal replacement therapy	13 (40.6)	23 (30.7)	0.438	31 (34.1)	5 (31.2)	1
Vasopressor use	18 (56.2)	34 (45.3)	0.41	49 (53.8)	3 (18.8)	0.013b
ICU LOS	10.0 (15.2)	8.0 (10.0)	0.513	9.0 (12.0)	5.0 (2.2)	0.003c
28-day transplant free survival	12 (37.5)	37 (49.3)	0.361	38 (41.8)	11 (68.8)	0.084
ICU survival	14 (43.8)	41 (54.7)	0.41	44 (48.4)	11 (68.8)	0.217
Hospital survival	10 (31.2)	35 (46.7)	0.206	34 (37.4)	11 (68.8)	0.038d
Hospital LOS (days)	27.0 (29.2)	21.0 (19.0)	0.083	24.0 (26.5)	14.0 (15.0)	0.03e

^aP < 0.01 for mechanical ventilation in infected vs non-infected patients.

^bP < 0.05 for vasopressor use in infected vs non-infected patients.

^cP < 0.01 for intensive care unit length of stay in infected vs non-infected patients.

^dP < 0.05 for hospital length of stay in infected vs non-infected patients.

^eP < 0.05 for hospital survival in infected vs non-infected patients.

¹P values were calculated using Fisher’s exact or Mann-Whitney U test, as appropriate.

LOS: Length of stay; ICU: Intensive care unit.

Table 4 Multivariable logistic regression model predicting multidrug-resistant organism infection during intensive care unit admission (n = 87)

Predictor	OR	95%CI	P value1
MDRO colonization	2.18	0.47-10.10	0.383
MELD-Na score	0.94	0.82-1.08	0.321
SOFA score	1.03	0.68-1.54	0.394
CLIF-ACLF score	1.11	0.99-1.23	0.903
Age	0.94	0.86-1.02	0.066
Sex (male vs female)	0.17	0.02-1.61	0.152

¹P values based on Wald test.

MDRO: Multidrug-resistant organism; MELD: Model for End-Stage Liver Disease; SOFA: Sequential Organ Failure Assessment; CLIF: Chronic liver failure; ACLF: Acute-on-chronic liver failure; OR: Odds ratio; CI: Confidence interval.

Table 5 Multivariable logistic regression model predicting 28-day transplant-free mortality in intensive care unit patients with cirrhosis (n = 87)

Predictor	OR	95%CI	P value1
MDRO colonization	1.14	0.37-3.50	0.813
MELD-Na score	0.99	0.91-1.08	0.829
SOFA score	1.38	1.04-1.83	0.024a
CLIF-ACLF score	1.07	1.00-1.16	0.062
Age	1.04	0.98-1.10	0.241
Sex (male vs female)	1.66	0.53-5.19	0.387

^aP < 0.05 for Sequential Organ Failure Assessment score as predictor of 28-day transplant-free mortality.

¹P values based on Wald test.

MDRO: Multidrug-resistant organism; MELD: Model for End-Stage Liver Disease; SOFA: Sequential Organ Failure Assessment; CLIF: Chronic liver failure; ACLF: Acute-on-chronic liver failure; OR: Odds ratio; CI: Confidence interval.

Table 6 Clinical outcomes stratified by decompensation phenotype (acute decompensation vs acute-on-chronic liver failure), n (%)/median (interquartile range)

Outcome	AD (n = 20)	ACLF (n = 87)	P value1
MDRO colonized	2 (10.0)	30 (34.5)	0.033a
Total infections	16 (80.0)	75 (86.2)	0.494
Strain-concordant infection	2 (100.0)	18 (81.8)	1.000
ICU length of stay (days)	5.0 (7.5)	9.0 (12.0)	0.084
28-day transplant-free survival	15 (75.0)	34 (39.1)	0.008b
ICU survival	17 (85.0)	38 (43.7)	0.001c
Hospital survival	15 (75.0)	30 (34.5)	0.002d
Hospital LOS (days)	20.5 (25.2)	24.0 (24.0)	0.946

^aP < 0.05 for multidrug-resistant organism colonization (acute-on-chronic liver failure vs acute decompensation).

^bP < 0.01 for 28-day transplant-free survival (acute-on-chronic liver failure vs acute decompensation).

^cP < 0.01 for intensive care unit survival (acute-on-chronic liver failure vs acute decompensation).

^dP < 0.01 for hospital survival (acute-on-chronic liver failure vs acute decompensation).

¹P values were calculated using Fisher’s exact or Mann-Whitney U test, as appropriate.

MDRO: Multidrug-resistant organism; ICU: Intensive care unit; LOS: Length of stay; AD: Acute decompensation; ACLF: Acute-on-chronic liver failure.