Carbapenem-resistant Klebsiella pneumoniae infections after liver transplantation: Drug resistance, risk factors and impact on prognosis

Table 1 Demographic, laboratory, and clinical variables of 430 liver transplant recipients, mean ± SD/n (%)

Characteristics	Value	Range
Recipient age (years)	47.2 ± 10.6	18-73
Recipient gender (female)	78 (18.1)
Recipient BMI (kg/m2), median (IQR)	22.8 (20.8-25.1)	13.8-37.1
Hospital stay prior to LT (days), median (IQR)	9.0 (1.0-22.0)	1-161
MELD score at LT, median (IQR)	23.0 (15.0-30.0)	6-40
Infection within 2 months prior to LT	170 (39.5)
Pre-LT use of broad-spectrum antibiotics	168 (39.1)
Underlying liver diseases	430 (100)
Viral cirrhosis/necrosis/tumor	319 (74.2)
Alcoholic cirrhosis	32 (7.4)
Autoimmune hepatitis	15 (3.5)
Primary biliary cirrhosis	13 (3.0)
Mixed cirrhosis	24 (5.6)
Others1	27 (6.0)
Pre-LT type 2 diabetes	51 (11.9)
Pre-LT creatinine (mg/dL), median (IQR)	0.8 (0.6-1.0)	0.1-10.7
Pre-LT WBC count (× 109/L), median (IQR)	5.2 (3.5-8.0)	0.5-33.6
Pre-LT lymphocyte count (× 109/L), median (IQR)	0.8 (0.5-1.2)	0.1-3.7
Pre-LT platelet count (× 109/L), median (IQR)	70.0 (43.0-106.3)	7.0-491.0
Pre-LT albumin level (g/L), median (IQR)	34.5 (30.7-38.0)	18.0-55.7
Donor age (years)	42.2 ± 13.1	7-68
Steatosis ≥ 30%	43 (10.0)
Cold ischemia time (hour)	6.3 ± 1.4	1.5-9.6
Duration of surgery (minutes), median (IQR)	380.0 (333.0-430.0)	185-710
Intraoperative bleeding (mL), median (IQR)	3000.0 (2000.0-5000.0)	500-27000
Intraoperative RBC transfusion (units), median (IQR)	12.0 (8.0-18.0)	0-44.0
Post-LT infections due to Klebsiella pneumoniae	33 (7.7)
Median interval between the onset of CRKP infections and LT (days), median (IQR)	6.5 (2.0-17.0)	1-116
CRKP infections	20 (4.7)
Post-LT immunosuppressant treatment	430 (100)
Tacrolimus	419 (97.4)
Ciclosporin A	5 (1.2)
Mycophenolate mofetil/enteric-coated mycophenolate sodium	299 (69.5)
Sirolimus	5 (1.2)
Glucocorticoid	430 (100)
Basiliximab	238 (55.3)
Anti-thymocyte globulin	18 (4.2)
ALT on day 1 after LT (U/L), median (IQR)	697.5 (385.0-1276.3)	54.0-8972.0
Creatinine on day 3 after LT (mg/dL), median (IQR)	0.9 (0.7-1.4)	0.3-12.6
Albumin level on day 1 after LT (g/L), median (IQR)	37.1 (33.6-40.6)	22.5-51.9
Post-LT mechanical ventilation	96 (22.3)
Reoperation	17 (4.0)
Acute rejection	68 (15.8)
Post-LT renal replacement therapy	19 (4.4)
ICU stay after LT (days), median (IQR)	6.0 (5.0-7.0)	0-32
Hospitalization stay after LT (days), median (IQR)	26.0 (21.0-30.0)	3-137
All-cause mortality within 6 months after LT	37 (8.6)
CRKP infections-related mortality	7 (1.6)

¹There were 10 cases of cryptogenic cirrhosis, 5 cases of Budd-Chiari syndrome, 3 cases each of hepatolenticular degeneration and transplant liver failure, 2 cases each of drug-induced liver injury, polycystic liver, and familial hereditary amyloidosis.

LT: Liver transplant; BMI: Body mass index; MELD: Model for end-stage liver disease; IQR: Interquartile range; WBC: White blood cell; RBC: Red blood cell; CRKP: Carbapenem-resistant Klebsiella pneumoniae; ALT: Alanine aminotransferase; ICU: Intensive care unit.

Table 2 Rate of drug-resistance of 32 isolates of carbapenem-resistant Klebsiella pneumoniae to 12 commonly used antibiotics

Antimicrobial	Number	Percentage
TZP	32	100
CAZ	32	100
CFS	32	100
FEP	32	100
ATM	32	100
MEM	32	100
LVF	32	100
AN	21	65.6
SXT	18	56.3
TIC	8	25.0
POL	3	9.4
CZA	2	6.3

ATM: Aztreonam; TZP: Piperacillin/tazobactam; CFS: Cefoperazone/ sulbactam; CAZ: Ceftazidime; FEP: Cefepime; AN: Amikacin; LVF: Levofloxacin; MEM: Meropenem; TIC: Tigecycline; SXT: Trimethoprim/sulfamethoxazole; POL: Polymixin B; CZA: Ceftazidime/avibactam.

Table 3 Univariate analysis of risk factors for carbapenem-resistant Klebsiella pneumoniae infections within 3 months after liver transplant, n (%)

Variables	With CRKP infections (n = 20)	Without CRKP infections (n = 410)	P value
Female sex	8 (40.0)	70 (17.1)	0.009
Recipient age ≥ 55 years	7 (35.0)	98 (23.9)	0.259
Recipient BMI ≥ 25	5 (25.0)	109 (26.6)	0.875
MELD score at LT ≥ 25	13 (65.0)	181 (44.1)	0.067
Hospital stay prior to LT ≥ 7 days	13 (65.0)	228 (55.6)	0.409
Viral cirrhosis/necrosis/tumor	14 (70.0)	306 (74.6)	0.643
Hepatic tumor	1 (5.0)	72 (17.6)	0.248
Alcoholic cirrhosis	2 (10.0)	30 (7.3)	0.992
Pre-LT diabetes	4 (20.0)	47 (11.5)	0.424
Pre-LT use of broad-spectrum antibiotics ≥ 3 days	11 (55.0)	157 (38.3)	0.135
Pre-LT creatinine ≥ 2 mg/dL	2 (10.0)	29 (7.1)	0.959
Infection within 2 months prior to LT	11 (55.0)	159 (38.8)	0.147
Pre-LT WBC count ≥ 10 × 109/L	2 (10.0)	59 (14.4)	0.825
Pre-LT lymphocyte count ≤ 0.5 × 109/L	3 (15.0)	103 (25.1)	0.447
Pre-LT platelet count ≤ 50 × 109/L	8 (40.0)	135 (32.9)	0.512
Pre-LT albumin level < 30 g/L	4 (20.0)	85 (20.7)	1.000
Donor age ≥ 50 years	8 (40.0)	134 (32.7)	0.497
Steatosis ≥ 30%	2 (10.0)	41 (10.0)	1.000
Cold ischemia time ≥ 360 minutes	11 (55.0)	193 (47.1)	0.488
Duration of surgery ≥ 450 minutes	8 (40.0)	74 (18.0)	0.015
Intraoperative bleeding ≥ 3000 mL	18 (80.0)	236 (57.6)	0.004
Intraoperative RBC transfusion ≥ 12 U/L	13 (65.0)	223 (54.4)	0.352
ALT on day 1 after LT ≥ 1500 U/L	10 (50.0)	74 (18.0)	< 0.001
Creatinine on day 3 after LT ≥ 2 mg/dL	3 (15.0)	60 (14.6)	1.000
Albumin level on day 1 after LT < 30 g/L	2 (10.0)	29 (7.1)	0.959
Post-LT mechanical ventilation	10 (50.0)	87 (21.2)	0.003
Reoperation	2 (10.0)	15 (3.7)	0.184
Acute rejection	3 (15.0)	65 (15.9)	1.000
Post-LT renal replacement therapy	3 (15.0)	16 (3.9)	0.052
Glucocorticoidse ≥ 1500 mg	15 (65.0)	249 (60.7)	0.702
Basiliximab use ≥ 40 mg	8 (40.0)	171 (41.7)	0.880
Anti-thymocyte globulin use	2 (10.0)	16 (3.9)	0.201

LT: Liver transplant; BMI: Body mass index; MELD: Model for end-stage liver disease; WBC: White blood cell; RBC: Red blood cell; CRKP: Carbapenem-resistant Klebsiella pneumoniae; ALT: Alanine aminotransferase.

Table 4 Multivariate logistic regression analysis of risk factors for carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients

Variables	B	S.E.	Wald	OR (95%CI)	P value
Female sex	1.196	0.501	5.700	3.306 (1.239-8.822)	0.017
Intraoperative bleeding ≥ 3000 mL	1.184	0.595	3.963	3.269 (1.018-10.490)	0.047
ALT on day 1 after LT ≥ 1500 U/L	1.475	0.486	9.215	4.370 (1.686-11.326)	0.002
Post-LT mechanical ventilation	1.020	0.482	4.469	2.772 (1.077-7.135)	0.035

ALT: Alanine aminotransferase; CI: Confidence interval; OR: Odds ratio.

Table 5 The postoperative outcome for patients with/without carbapenem-resistant Klebsiella pneumoniae infections following liver transplant, n (%)

Variables	With CRKP infections (n = 20)	Without CRKP infections (n = 410)	χ2	P value
ICU stay after LT ≥ 7 days	14 (70.0)	141 (34.4)	10.490	0.001
Hospitalization stay after LT ≥ 21 days	16 (80.0)	326 (19.5)	0.003	1.000
All-cause mortality within 6 months after LT	7 (35.0)	30 (7.3)	18.583	< 0.001

CRKP: Carbapenem-resistant Klebsiella pneumoniae; LT: Liver transplant; ICU: Intensive care unit.