Klebsiella pneumoniae infections after liver transplantation: Drug resistance and distribution of pathogens, risk factors, and influence on outcomes

Table 1 Demographic, laboratory, and clinical variables of 406 liver transplantation recipients

Characteristics	Value
Recipient age (yr), mean ± SD	47.3 ± 10.6
Recipient gender, no. of female (%)	72 (17.7)
Recipient BMI, median (IQR), kg/m2	22.8 (20.8-25.1)
Hospital stay prior to LT, median (IQR), days	10.0 (1.0-22.3)
MELD score at LT, median (IQR)	23.0 (15.0-30.0)
Infection within 2 months prior to LT, n (%)	160 (39.4)
Pulmonary infection	140 (34.5)
Abdominal/biliary infection	6 (1.5)
Urinary tract infection	1 (0.2)
Multiple site infection1	13 (3.2)
Pre-LT use of broad-spectrum antibiotics	166 (40.9)
Underlying liver diseases, n (%)	406 (100)
Viral cirrhosis/necrosis/tumor	304 (74.9)
Alcoholic cirrhosis	31 (7.6)
Autoimmune hepatitis	15 (3.7)
Primary biliary cirrhosis	11 (2.7)
Mixed cirrhosis	19 (4.7)
Others2	26 (6.4)
Pre-LT type 2 diabetes, n (%)	48 (11.8)
Pre-LT creatinine, median (IQR), mg/dL	0.8 (0.7-1.0)
Pre-LT WBC count, median (IQR), × 109/L	5.2 (3.4-8.1)
Pre-LT lymphocyte count, median (IQR), × 109/L	0.8 (0.5-1.2)
Pre-LT platelet count, median (IQR), × 109/L	72 (43.8-106.5)
Pre-LT albumin level, median (IQR), g/L	34.5 (30.9-38.1)
Donor age (yr), mean ± SD	42.1 ± 13.0
Steatosis ≥ 30%, n (%)	42 (10.3)
Cold ischemia time, mean ± SD	6.2 ± 1.5
Duration of surgery, median (IQR), min	378.5 (333.0-425.0)
Intraoperative bleeding, median (IQR), mL	3000.0 (2000.0-5000.0)
Intraoperative RBC transfusion, median (IQR), units	12.0 (8.0-18.0)
Post-LT infections due to Klebsiella pneumoniae, n (%)	32 (7.9)
Post-LT infections due to CRKP, n (%)	21 (5.2)
Median interval between the onset of infections due to Klebsiella pneumoniae and LT, median (IQR), days	7.5 (2.0-17.8)
Post-LT immunosuppressant treatment, n (%)	406 (100)
Tacrolimus	395 (97.3)
Ciclosporin A	5 (1.2)
Mycophenolate mofetil/enteric-coated mycophenolate sodium	277 (68.2)
Sirolimus	5 (1.2)
Glucocorticoid	406 (100)
Basiliximab	214 (52.7)
Anti-thymocyte globulin	18 (4.4)
ALT on day 1 after LT, median (IQR), U/L	694.5 (383.0-1242.0)
Creatinine on day 3 after LT, median (IQR), mg/dL	0.9 (0.7-1.4)
Albumin level on day 1 after LT, median (IQR), g/L	37.2 (33.9-40.7)
Post-LT duration of urethral catheter, median (IQR), days	3.0 (2.0-5.0)
Post-LT mechanical ventilation, n (%)	94 (23.2)
Reoperation, n (%)	17 (4.2)
Acute rejection, n (%)	67 (16.5)
Post-LT renal replacement therapy, n (%)	19 (4.7)
ICU stay after LT, median (IQR), days	6.0 (5.0-7.0)
Hospitalization stay after LT, median (IQR), days	26.0 (21.0-30.0)
All-cause mortality within 6 months after LT, n (%)	32 (7.9)

¹There were 9 cases of pulmonary and abdominal/bile duct infections, 1 case of pulmonary and urinary tract infections, 1 case of pulmonary and bloodstream infections, 1 case of pulmonary and intracranial infections, and 1 case each of pulmonary, abdominal and bloodstream infections.

²There were 9 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.

ALT: Alanine aminotransferase; BMI: Body mass index; ICU: Intensive care unit; Fis: Fungal infections; IQR: Interquartile range; LT: Liver transplantation; MELD: Model for End-Stage Liver Disease; RBC: Red blood cell.

Table 2 Infection sites of 44 episodes of infections caused by Klebsiella pneumoniae

Infection sites	Lung/thoracic cavity	Blood stream	Abdominal/biliary tract	Urinary tract	Perianal abscess	Liver abscess
Klebsiella pneumoniae (44)	15	12	12	3	1	1

Table 3 Rate of drug-resistance of 44 isolates of Klebsiella pneumoniae to 12 commonly used antibiotics, n (%)

Antimicrobial	n	Percentage
TZP	34	77.3
CAZ	31	70.5
CFS	30	68.2
FEP	31	70.5
ATM	31	70.5
MEM	31	70.5
AN	21	47.7
LVF	33	75.0
SXT	20	45.5
TIC	10	22.7
POL	1	2.3
CAZ/AVI	1	2.3

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; CAZ/AVI: Ceftazidime/avibactam.

Table 4 Univariate and multivariate logistic regression analysis of risk factors for infections due to Klebsiella pneumoniae within 3 months after liver transplantation, n (%)

Variables	With K. pneumoniae infections(32)	Without K. pneumoniae infections(374)	P value	OR (95%CI)
Total
Univariate analysis
Female sex	12 (37.5)	60 (16.0)	0.002
Recipient age ≥ 55 yr	10 (31.3)	91 (24.3)	0.385
Recipient BMI ≥ 25	9 (28.1)	97 (25.9)	0.787
MELD score at LT ≥ 22	23 (71.9)	206 (55.1)	0.066
Hospital stay prior to LT ≥ 7 d	23 (71.9)	216 (57.8)	0.119
Viral cirrhosis/necrosis/tumor	21 (65.6)	283 (75.7)	0.209
Alcoholic cirrhosis	3 (9.4)	28 (7.5)	0.969
Pre-LT diabetes	7 (21.9)	41 (11.0)	0.067
Pre-LT use of broad-spectrum antibiotics ≥ 3 d	16 (50.0)	150 (40.1)	0.275
Pre-LT creatinine ≥ 2 mg/dL	1 (3.1)	28 (7.5)	0.574
Infection within 2 months prior to LT	17 (53.7)	143 (38.2)	0.098
Pre-LT WBC count ≥ 10 × 109/L	4 (12.5)	55 (14.7)	0.937
Pre-LT lymphocyte count ≤ 0.5 × 109/L	6 (18.8)	92 (24.6)	0.458
Pre-LT platelet count ≤ 50 × 109/L	12 (37.5)	123 (32.9)	0.595
Pre-LT albumin level < 30 g/L	9 (28.1)	71 (19.0)	0.212
Donor age ≥ 50 yr	13 (40.6)	121 (32.4)	0.340
Steatosis ≥ 30%	2 (6.3)	40 (10.7)	0.624
Cold ischemia time ≥ 360 min	15 (46.9)	189 (50.5)	0.691
Duration of surgery ≥ 450 min	10 (31.3)	61 (16.3)	0.033
Intraoperative bleeding ≥ 3000 mL	23 (71.9)	214 (57.2)	0.101
Intraoperative RBC transfusion ≥ 12 U	20 (62.5)	201 (53.7)	0.340
ALT on day 1 after LT ≥ 1500U/L	14 (43.8)	66 (17.6)	<0.001
Creatinine on day 3 after LT ≥ 2 mg/dL	4 (12.5)	57 (15.2)	0.874
Albumin level on day 1 after LT < 30 g/L	4 (12.5)	24 (6.4)	0.347
Post-LT duration of urethral catheter ≥ 4 d	22 (68.8)	167 (44.7)	0.009
Post-LT mechanical ventilation	13 (40.6)	81 (21.7)	0.015
Reoperation	3 (9.4)	14 (3.7)	0.286
Acute rejection	6 (18.8)	61 (16.3)	0.721
Post-LT renal replacement therapy	3 (9.4)	16 (4.3)	0.382
Glucocorticoidse ≥ 1500 mg	21 (65.6)	235 (62.8)	0.754
Basiliximab use ≥ 40 mg	14 (43.8)	145 (38.8)	0.580
Anti-thymocyte globulin use	4 (12.5)	14 (3.7)	0.063
Multivariate analysis
Female sex			0.012	2.827 (1.256-6.364)
Pre-LT diabetes			0.036	2.794 (1.070-7.294)
ALT on day 1 after LT ≥ 1500U/L			0.001	3.645 (1.671-7.950)
Post-LT duration of urethral catheter ≥ 4 d			0.046	2.266 (1.016-5.054)

ALT: Alanine aminotransferase; BSIs: Bloodstream infections; CI: Confidence intervals; LT: Liver transplantation; MELD: Model for End-Stage Liver Disease; OR: Odds ratios; RBC: Red blood cell; BMI: Body mass index; K. pneumoniae: Klebsiella pneumoniae.

Table 5 The postoperative outcome for patients with/without infections caused by Klebsiella pneumoniae following liver transplantation, n (%)

Variables	With infections caused by K. pneumoniae(32)	Without infections caused by K. pneumoniae (374)	χ2	P value
ICU stay after LT ≥ 7 d	18 (56.3)	132 (35.3)	5.557	0.018
Hospitalization stay after LT ≥ 21 d	26 (81.3)	302 (80.7)	0.288	0.592
All-cause mortality within 6 months after LT	6 (18.8)	32 (8.6)	5.651	0.017

ICU: Intensive care unit; LT: Liver transplantation; K. pneumoniae: Klebsiella pneumoniae

Table 6 Univariate and multivariate Logistic regression analysis of risk factors for 6-month all-cause mortality after liver transplantation, n (%)

Variables	Death(32)	Survival(374)	P value	OR (95%CI)
Total
Univariate analysis
Female sex	10 (31.3)	62 (16.6)	0.037
Recipient age ≥ 55 yr	14 (43.8)	87 (23.3)	0.010
Recipient BMI ≥ 25	4 (12.5)	102 (27.3)	0.068
MELD score at LT ≥ 22	24 (75.0)	205 (54.8)	0.027
Hospital stay prior to LT ≥ 7 d	24 (75.0)	215 (57.5)	0.053
Viral cirrhosis/necrosis/tumor	25 (78.1)	279 (74.6)	0.659
Alcoholic cirrhosis	1 (3.1)	30 (8.0)	0.513
Pre-LT diabetes	4 (12.5)	44 (11.8)	1.000
Pre-LT creatinine ≥ 2 mg/dL	6 (18.8)	23 (6.1)	0.008
Infection within 2 months prior to LT	19 (59.4)	141 (37.7)	0.016
Pre-LT WBC count ≥ 10 × 109/L	7 (21.9)	52 (13.9)	0.219
Pre-LT lymphocyte count ≤ 0.5 × 109/L	12 (37.5)	86 (23.0)	0.066
Pre-LT platelet count ≤ 50 × 109/L	8 (25.0)	127 (34.0)	0.302
Pre-LT albumin level < 30g/L	6 (18.8)	74 (19.8)	0.888
Donor age ≥ 50 yr	7 (21.9)	127 (34.0)	0.163
Steatosis ≥ 30%	3 (9.4)	39 (10.4)	1.000
Cold ischemia time ≥ 360 min	20 (62.5)	199 (53.2)	0.248
Duration of surgery ≥ 450 min	8 (25.0)	63 (16.8)	0.244
Intraoperative bleeding ≥ 3000 mL	26 (81.3)	211 (56.4)	0.006
Intraoperative RBC transfusion ≥ 12 U	25 (78.1)	196 (52.4)	0.005
ALT on day 1 after LT ≥ 1500 U/L	8 (25.0)	72 (19.3)	0.433
Creatinine on day 3 after LT ≥ 2 mg/dL	18 (56.3)	43 (11.5)	< 0.001
Albumin level on day 1 after LT < 30 g/L	6 (18.8)	25 (6.7)	0.564
Post-LT infections due to Klebsiella pneumoniae	6 (18.8)	26 (7.0)	0.017
Post-LT infections due to CRKP	6 (18.8)	15 (4.0)	< 0.001
Post-LT mechanical ventilation	19 (59.4)	75 (20.1)	< 0.001
Reoperation	3 (9.4)	14 (3.7)	0.286
Acute rejection	4 (12.5)	63 (16.8)	0.525
Post-LT renal replacement therapy	8 (25.0)	11 (2.9)	< 0.001
Glucocorticoidse ≥ 1500 mg	19 (59.4)	237 (63.4)	0.653
Basiliximab use ≥ 40 mg	10 (31.3)	149 (39.8)	0.339
Anti-thymocyte globulin use	1 (3.1)	17 (4.5)	1.000
Multivariate analysis
Female sex			0.031	2.829 (1.098-7.288)
Intraoperative RBC transfusion ≥ 12 U			0.016	3.466 (1.259-9.543)
Creatinine on day 3 after LT ≥ 2 mg/dL			< 0.001	9.724 (4.077-23.194)
Post-LT infections due to CRKP			0.008	5.330 (1.534-18.524)
Post-LT mechanical ventilation			0.001	4.118 (1.790-9.476)

ALT: Alanine aminotransferase; CI: Confidence intervals; LT: Liver transplantation; RBC: Red blood cell; MELD: Model for End-Stage Liver Disease; OR: Odds ratios; BMI: Body mass index.

Table 7 Univariate and multivariate Logistic regression analysis of risk factors for intensive care unit stay after liver transplantation ≥ 7, n (%)

Variables	ICU stay after LT ≥ 7 d (150)	ICU stay after LT < 7 d (256)	P value	OR (95%CI)
Total
Univariate analysis
Female sex	34 (22.7)	38 (14.8)	0.046
Recipient age ≥ 55 yr	45 (30.0)	56 (21.9)	0.068
Recipient BMI ≥ 25	38 (25.3)	68 (26.6)	0.785
MELD score at LT ≥ 22	98 (65.3)	131 (51.2)	0.005
Hospital stay prior to LT ≥ 7 d	98 (65.3)	141 (55.1)	0.043
Viral cirrhosis/necrosis/tumor	112 (74.7)	192 (75.0)	0.940
Alcoholic cirrhosis	11 (7.3)	20 (7.8)	0.861
Pre-LT diabetes	17 (11.3)	31 (12.1)	0.815
Pre-LT creatinine ≥ 2 mg/dL	18 (12.0)	11 (4.3)	0.004
Infection within 2 months prior to LT	57 (38.0)	103 (40.2)	0.657
Pre-LT WBC count ≥ 10 × 109/L	27 (18.0)	123 (48.0)	0.129
Pre-LT lymphocyte count ≤ 0.5 × 109/L	34 (22.7)	64 (25.0)	0.596
Pre-LT platelet count ≤ 50 × 109/L	46 (30.7)	89 (34.8)	0.397
Pre-LT albumin level < 30 g/L	28 (18.7)	123 (48.0)	0.687
Donor age ≥ 50 yr	46 (30.7)	88 (34.4)	0.443
Steatosis ≥ 30%	16 (10.7)	26 (10.2)	0.871
Cold ischemia time ≥ 360 min	78 (52.0)	136 (53.1)	0.827
Duration of surgery ≥ 450 min	31 (20.7)	40 (15.6)	0.197
Intraoperative bleeding ≥ 3000 ml	102 (68.0)	135 (52.7)	0.003
Intraoperative RBC transfusion ≥ 12 U	92 (61.3)	129 (50.4)	0.033
ALT on day 1 after LT ≥ 1500 U/L	41 (27.3)	39 (15.2)	0.003
Creatinine on day 3 after LT ≥ 2 mg/dL	30 (20.0)	31 (12.1)	0.032
Albumin level on day 1 after LT < 30 g/L	12 (8.0)	16 (6.3)	0.502
Post-LT infections due to Klebsiella pneumoniae	18 (12.0)	14 (5.5)	0.018
Post-LT infections due to CRKP	15 (10.0)	6 (2.3)	0.001
Post-LT mechanical ventilation	59 (39.3)	35 (13.7)	< 0.001
Reoperation	11 (7.3)	6 (2.3)	0.015
Acute rejection	28 (18.7)	39 (15.2)	0.369
Post-LT renal replacement therapy	14 (9.3)	5 (2.0)	0.001
Glucocorticoidse ≥ 1500 mg	102 (68.0)	154 (60.2)	0.114
Basiliximab use ≥ 40 mg	55 (36.7)	104 (40.6)	0.430
Anti-thymocyte globulin use	7 (4.7)	11 (4.3)	0.861
Multivariate analysis
MELD score at LT ≥ 22			0.020	1.695 (1.086-2.645)
Intraoperative bleeding ≥ 3000 ml			0.012	1.790 (1.139-2.813)
ALT on day 1 after LT ≥ 1500 U/L			0.017	1.915 (1.123-3.265)
Post-LT renal replacement therapy			0.014	4.058 (1.327-12.409)
Post-LT mechanical ventilation			< 0.001	3.402 (2.052-5.639)

ICU: Intensive care unit; ALT: Alanine aminotransferase; CI: Confidence intervals; LT: Liver transplantation; RBC: Red blood cell; MELD: Model for End-Stage Liver Disease; OR: Odds ratios; CRKP: Carbapenem-resistant Klebsiella pneumoniae; BMI: Body mass index.