High mortality associated with gram-negative bacterial bloodstream infection in liver transplant recipients undergoing immunosuppression reduction

Table 1 Characteristics of liver transplant recipients with bloodstream infection in terms of bacterial pathogens, n (%)

Variable	Gram-positive BSI, n = 42	Gram-negative BSI, n = 28	P value
Age in yr, mean ± SD	51.0 ± 10.5	47.66 ± 13.01	0.228
Female sex	9 (21.4)	8 (28.6)	0.495
Etiology of liver transplant
Hepatocellular carcinoma	13 (31.0)	7 (25.0)	0.589
Hepatitis B virus	20 (47.6)	13 (46.4)	0.922
Others	9 (21.4)	8 (28.6)	0.495
Baseline immunosuppressive treatment
Prednisone	18 (42.9)	12 (42.9)	0.596
Tacrolimus	31 (73.8)	18 (64.3)	0.833
Cyclosporin	7 (16.7)	5 (17.9)	0.897
Mycophenolate mofetil	35 (83.3)	17 (60.7)	0.034
BSI characteristics
Early BSI1	41 (97.6)	26 (92.9)	0.718
Septic shock	0	4 (14.3)	NA
BSI source, episodes	n = 45	n = 29
Primary	10 (23.8)	3 (10.7)	0.318
Surgical wound	20 (47.6)	0	NA
Biliary tract	5 (11.9)	7 (25.0)	0.246
Urinary tract	1 (2.4)	6 (21.4)	0.025
Central venous catheter	2 (4.8)	2 (7.1)	0.649
Intra-abdominal	1 (2.4)	9 (32.1)	0.001
Respiratory tract	6 (14.3)	5 (17.9)	0.833
Management of infection
Empiric therapy	31 (73.8)	14 (50.0)	0.126
Target therapy	11 (26.2)	12 (42.9)	0.201
Source control	2 (4.8)	3 (10.7)	0.608
Length of stay in d, median (IQR)	18 (15-26.8)	24.5 (18-39)	0.055
From the day of transplantation to onset of BSI in d, median (IQR)	4 (1-6)	12 (8-41)	0.048
Patient outcome
Died	2 (4.8)	11 (39.3)	0.001
Suspected rejection2	3 (7.1)	7 (25.0)	0.081
Microbiological clearance	43 (95.6)	18 (62.1)	0.001
IS reduction	5 (11.9)	23 (82.1)	< 0.001
Complete IS withdrawal	3 (7.1)	15 (53.6)	< 0.001
Length of IS withdrawal in d	6.3 (2-10)	12.6 (4-25)	0.171

¹Within 6 mo after liver transplantation.

²Within 90 d after bloodstream infection. BSI: bloodstream infection; IQR: Interquartile range; IS: Immunosuppression; NA: Not applicable; SD: Standard deviation.

Table 2 Distribution of the bacterial pathogens causing bloodstream infections in liver transplant recipients

Gram stain	Bacterial species	n (%)	Resistant strain, n
Gram-positive, n = 45	Enterococcus faecium	4 (8.89)	XDR, 1
	Staphylococcus aureus	3 (6.67)
	Enterococcus faecalis	4 (8.89)
	Streptococcus	2 (4.44)
	Coagulase negative Staphylococcus	24 (4.44)
	Others	8 (17.78)
Gram-negative, n = 29	Klebsiella pneumoniae	11 (37.93)	CRKP, 8; PDR, 1
	Acinetobacter baumannii	7 (24.14)	CRAB, 7
	Escherichia coli	5(17.24)	ESBL, 2; XDR, 1
	Pseudomonas aeruginosa	3 (10.34)	CRPA, 1; MDR, 2
	Others	3 (10.34)

CRAB: Carbapenem-resistant Acinetobacter baumannii; CRKP: Carbapenem-resistant Klebsiella pneumoniae; CRPA: Carbapenem-resistant Pseudomonas aeruginosa; ESBL: Extended spectrum beta-lactamase; MDR: Multidrug-resistant; PDR: Pandrug-resistant; XDR: Extensively drug-resistant.

Table 3 Relationship of clinical and therapeutic variables with outcomes in patients with Gram-negative bacterial infections, n (%)

Variable	30 d mortality, n = 11	30 d survival, n = 17	P value
Age in yr, mean ± SD	48.09 ± 15.4	47.29 ± 12.2	0.88
Female sex	2 (18.2)	6 (35.3)	0.419
Etiology of liver transplant
Hepatocellular carcinoma	13 (31.0)	7 (25.0)	0.419
Hepatitis B virus	20 (47.6)	13 (46.4)	0.934
BSI source, episodes
Primary	0	2 (11.8)	0.505
Respiratory tract	3 (27.3)	2 (11.8)	0.353
Intra-abdominal	4 (36.4)	5 (29.4)	0.7
Biliary tract	5 (45.5)	2 (11.8)	0.076
Urinary tract	1 (9.1)	5 (29.4)	0.355
Management of infection
Empiric therapy	3 (27.3)	11 (64.7)	0.053
Target therapy	7 (63.6)	5 (29.4)	0.074
Source control	1 (9.1)	1 (5.9)	0.747
Patient outcome
Suspected rejection1	6 (54.5)	1 (5.9)	0.007
Pathogen
Acinetobacter baumannii	5 (45.5)	2 (11.1)	0.044
Klebsiella pneumoniae	6 (54.5)	5 (29.4)	0.184
Management of immunosuppressive therapy
IS reduction	1 (9.1)	7 (41.2)	0.099
Complete IS withdrawal	10 (90.9)	5 (29.4)	0.002

¹Within 90 d after liver transplantation. BSI: bloodstream infection; IS: Immunosuppression; SD: Standard deviation.

Table 4 Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality after Gram-negative bacterial infections in liver transplant recipients

Variable	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	aHR (95%CI)	P value
Age	1.025 (0.969-1.085)	0.392
Sex	0.778 (0.157-3.857)	0.759
Etiology of liver transplant
Hepatocellular carcinoma	0.839 (0.169-4.157)	0.829
Hepatitis B virus	0.666 (0.159-2.79)	0.578
Rejection1	13.89 (2.741-70.376)	0.001	7.021 (1.581-31.188)	0.01
BSI source
Primary	0.044 (0.00-3.849)	0.581
Respiratory tract	1.987 (0.448-8.81)	0.366
Intra-abdominal	1.343 (0.391-4.611)	0.639
Biliary tract	2.376 (0.72-7.843)	0.156
Urinary tract	0.51 (0.063-4.146)	0.529
Pathogen
Klebsiella pneumoniae	5.165 (1.22-21.87)	0.026		0.47
Acinetobacter baumannii	0.038 (0.00-125.635)	0.428
Management of infection
Empiric therapy	0.545 (0.13-2.282)	0.406
Target therapy	1.539 (0.384-6.163)	0.543
Source control	1.6 (0.197-13.018)	0.661
Management of immunosuppressive therapy
IS reduction	0.026 (0.0-12.782)	0.249
Complete IS withdrawal	14.362 (1.818-113.46)	0.012	12.65 (1.51-105.965)	0.019

¹Within 90 d after bloodstream infection. aHR: Adjusted hazard ratio; BSI: Bloodstream infection; CI: Confidence interval; HR: Hazard ratio; IS: Immunosuppression.