Comparison of Ceftizoxime Plus Ampicillin-Sulbactam versus Gentamicin Plus Ampicillin-Sulbactam in the Prevention of Post-Transplant Early Bacterial Infections in Liver Transplant Recipients: A Randomized Controlled Trial

Figures & data

Table 1 Classifications of Kidney Function According to RIFFLE Criteria

Stage	GFR Criteria	Urine Output Criteria
Risk	Increased serum creatinine 1.5 times or GFR decrease >25%	<5 mL/kg/h for 6 h
Injury	Increased serum creatinine 2 times or GFR decrease > 50%	<5 mL/kg/h for 12 h
Failure	Increased serum creatinine 3 times or GFR decrease > 75% or serum creatinine > 4 mg/dL	<3 mL/kg/h for 24 h or anuria for 12 h
Loss	Complete loss of kidney function > 4 weeks
ESKD	End stage kidney disease (> 3 months)

Abbreviation: GFR, glomerular filtration rate.

Figure 1 CONSORT diagram of the participants.

Table 2 Baseline Demographic, Clinical and Laboratory Data of Patients Between Ceftizoxime and Gentamicin Groups

Variable		Gentamicin Group (n=114)	Ceftizoxime Group (n=110)	Pvalue
Age (year) (mean±SD)		43.92±12.92	44.72±13.43	0.56
Gender (N, %)	Male	76 (66.6)	68 (61.81)	0.53
Female	38 (33.33)	42 (38.18)
BMI (kg/m^2)		22.69±3.50	23.85±4.51	0.21
MELD Score		17.53±5.85	19.67±7.21	0.22
Length of operation (minute)		303.62±63.00	290.41±78.02	0.19
Indication for transplantation (N)	Hepatitis B virus	13	18	0.16
	Primary sclerosing cholangitis	36	14
	Cryptogenic cirrhosis	13	19
	Wilson disease	5	4
	Hepatocellular carcinoma	6	4
	Autoimmune hepatitis	13	27
	Nonalcoholic steatohepatitis	11	9
	Hepatitis C virus	6	4
	Alcoholic liver disease	0	3
	Others	7	7
Albumin before transplantation (mg/dl)		2.56±0.56	2.53±0.59	0.99
WBC before transplantation (10^9/L)		10.01±5.07	9.71±5.96	0.21
Biliary anastomosis(%)	Choledochocholedochostomy	86(75.44)	71(64.55)	0.23
Choledochojejunostomy	28(24.56)	39(35.45)
Comorbid disease(N)	Diabetes mellitus	17	7	0.16
	Hypertension	1	2
	Asthma	2	4
	Duodenal ulcer/gastric ulcer	3	0
	DVT	2	2

Abbreviations: BMI, body mass index; MELD, model for end-stage liver disease; WBC, white blood cells; DVT, deep vein thrombosis.

Table 3 Comparison of Different Demographic, Clinical and Para Clinical Characteristics Between Patients with and Without Early Bacterial Infection After Liver Transplantation

Parameter	Univariate		Multivariate
	OR (95% CI)	P value	OR (95% CI)	P value
Age	0.995 (0.972–1.018)	0.668	–	–
Gender	0.629 (0.340–1.162)	0.139	–	–
BMI	0.924 (0.845–1.011)	0.08	–	–
MELD score	0.934 (0.891–0.980)	0.005	0.940 (0.876–1.009)	0.086
ICU length of stay	0.814 (0.748–0.886)	<0.001	0.948 (0.832–1.080)	0.422
Hospital length of stay	0.778 (0.716–0.845)	<0.001	0.782 (0.704–0.868)	<0.001
Underlying disease	0.963 (0.860–1.078)	0.512	–	–
Type of surgery	0.763 (0.335–1.737)	0.519	–	–
Biliary anastomosis	1.319 (0.533–3.261)	0.549	–	–
Length of operation	0.997 (0.750–1.326)	0.986	–	–
Reoperation	8.626 (2,90–25.5)	<0.001	3.056 (0.477–19.573)	0.238
History of antibiotic therapy within 1 week before transplantation	1.859 (0.957–3.60)	0.068	–	–
History of hospitalization within 3 months before transplantation	1.973 (1.031–3.776)	0.040	1.439 (0.530–3.904)	0.475
Mechanical ventilation more than 48 hr after transplantation	32.329 (10.520–99.345)	<0.001	–	–
WBC before transplantation	0.989 (0.937–1.044)	0.688	–	–
Type of prophylactic antibacterial regimen	0.245 (0.126–0.477)	<0.001	0.619 (0.244–1.571)	0.313

Abbreviations: BMI, body mass index; MELD, model for end-stage liver disease; ICU, intensive care unit.

Table 4 Comparison of Clinical Outcome Between Ceftizoxime and Gentamicin Groups

Variables			Gentamicin Group	Ceftizoxime Group	Pvalue
Bacterial infection(%)			15 (13.16)	42 (38.18)	<0.01
Length of ICU stay (days)			7.84±3.56	11.25±11.43	<0.001
Length of hospital stay (days)			13.22±4.80	17.48±11.14	<0.001
Mortality (N)			3	16	<0.001
Rejection episodes(N)			6	3	0.33
Type of infections (N)	VAP		3	22	<0.001
	Urinary tract infection		5	3
	Surgical site infection		2	3
	Bloodstream infection		1	2
	Co-infection	VAP+UTI	2	5
		VAP+ Surgical site infection	1	4
		VAP+ Bloodstream infection	1	1
		Surgical site infection + Bloodstream infection	0	1
Timing of infection after transplantation (day)			7.46±4.53	5.69±3.1	0.08
FK level (ng/mL)			5.46±4.23	5.24±4.34	0.34
VRE colonization (N)			21	18	0.1

Abbreviations: ICU, intensive care unit; VAP, ventilator-associated pneumonia; MRSA, methicillin-resistant Staphylococcus aureus; FK, tacrolimus; UTI, urinary tract infection.

Table 5 Comparison of Different Renal Function Indexes Between Ceftizoxime and Gentamicin Groups

Variables		Gentamicin Group(N=114)	Ceftizoxime Group(N=110)	Pvalue
Baseline GFR (mL/min)		105.06±43.56	95.100±40.44	0.92
GFR one week after transplantation (mL/min)		104.10±37.85	92.75±49.35	0.16
Hemodialysis or CRRT (N)		12	14	0.23
Episodes of ATN (N)		23	18	0.38
RIFLE Criteria	Risk (N)	8	12	0.07
	Injury (N)	5	5
	Failure (N)	8	10
	Loss (N)	0	1

Abbreviations: GFR, glomerular filtration rate; CRRT, continuous renal replacement therapies; ATN, acute tubular necrosis; FENa, fractional excretion of sodium.

Figure 2 The mean changes of serum creatinine level during the first 10 days after liver transplantation.

Table 6 Comparison of Different Demographic, Clinical and Para Clinical Characteristics Between Patients with and Without aminoglycoside nephrotoxicity After Liver Transplantation

Parameter	Univariate		Multivariate
	OR (95% CI)	P value	OR (95% CI)	P value
Age	1.005 (0.980–1.031)	0.693	–	–
Sex	2.305 (1.170–4.538)	0.016	1.930 (0.825–4.515)	0.129
BMI	1.005 (0.909–1.111)	0.927	–	–
MELD score	0.980 (0.928–1.035)	0.468	–	–
Length of ICU stay	1.052 (1.017–1.088)	0.004	1.067 (0.975–1.167)	0.161
Length of hospital stay	1.044 (1.010–1.0.078)	0.010	0.952 (0.873–1.038)	0.267
Bacterial infection after transplant	0.336 (0.167–0.679)	0.002	0.613 (0.179–2.093)	0.435
Underlying disease	1.082 (0.959–1.222)	0.201	–	–
Baseline GFR	1.002 (0.994–1.009)	0.618	–	–
FK level	1.016 (0.934–1.101)	0.712	–	–
Type of surgery	1.817 (0.758–4.358)	0.181	–	–
Biliary anastomosis	1.103 (0.414–2.944)	0.844	–	–
Length of operation	0.918 (0.666–1.256)	0.599	–	—
Reoperation	0.235 (0.086–647)	0.005	0.527 (0.117–2.366)	0.403
History of antibiotic therapy within 1 week before liver transplant	0.871 (0.467–1.838)	0.827	–	–
Mechanical ventilation more than 48 hr after transplantation	0.252 (0.109–0.584)	0.001	1.053 (0.263–4.217)	0.941
Rejection episodes	0.849 (0.170–4.240)	0.842	–	–
Concomitant use of nephrotoxic agent(s)	0.474 (0.247–0.907)	0.024	0.743 (0.250–2.208)	0.593
Level of hemoglobin before transplantation	0.811 (0.659–0.998)	0.047	0.809 (0.619–1.059)	0.123
Level of albumin before transplantation	0.709 (0.386–1.304)	0.269	–	–
Level of total bilirubin before transplantation	1.071 (1.024–1.120)	0.003	1.052 (0.925–1.195)	0.441
Level of direct bilirubin before transplantation	1.134 (1.044–1.232)	0.003	1.075 (0.844–1.371)	0.557
Level of ALT before transplantation	1.001 (1.000–1.001)	<0.001	1.001 (1.000–1.001)	0.005
Type of prophylactic antibacterial regimen	2.292 (1.145–4.587)	0.019	0.981 (0.402–2.391)	0.966

Abbreviations: BMI, body mass index; MELD, model for end-stage liver disease; ICU, intensive care unit; GFR, glomerular filtration rate; FK, tacrolimus; ALT, alanine transaminase.