Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study

Table 1 List of antibiotics included in the study

ATC code	Type of antibiotics
J01AA	Tetracyclines
J01BA	Amphenicols
J01BB	Macrolides, lincosamides and streptogramins
J01CA	Penicillins with extended spectrum
J01CE	Beta-lactamase sensitive penicillins
J01CF	Beta-lactamase resistant penicillins
J01CR	Combinations of penicillins, including beta-lactamase inhibitors
J01DB	First-generation cephalosporins
J01DC	Second-generation cephalosporins
J01DD	Third-generation cephalosporins
J01DE	Fourth-generation cephalosporins
J01DF	Monobactams
J01DH	Carbapenems
J01EA	Trimethoprim and derivatives
J01EB	Short-acting sulfonamides
J01EC	Intermediate-acting sulfonamides
J01ED	Long-acting sulfonamides
J01EE	Combinations of sulfonamides
J01FA	Macrolides
J01FF	Lincosamides
J01FG	Streptogramins
J01GA	Aminoglycoside antibacterials
J01GB	Other aminoglycosides
J01MA	Fluoroquinolones
J01MB	Other quinolone antibacterials
J01XA	Glycopeptide antibacterials
J01XB	Polymyxins
J01XC	Steroid antibacterials
J01XD	Imidazole derivatives
J01XE	Nitrofuran derivatives
J01XX	Other antibacterials

ATC: Anatomical Therapeutic Chemical.

Table 2 Distribution of facilities and cases across regions in Japan

Region	Number of facilities	Number of cases
Hokkaido	3	34
Tohoku	2	5
Kanto	14	319
Chubu	5	32
Kansai	11	359
Chugoku/Shikoku	1	2
Kyushu/Okinawa	10	229

Table 3 Patient characteristics, missing data, and comparison of standardized mean differences, n (%)

	Before Imputation and IPTW				After imputation and IPTW
	Prophylactic groups	Non-prophylactic groups	Missing (%)	SMD	SMD
Variables	n = 232	n = 558
Age, yr			0	0.18	0.01
< 65	143 (61.6)	322 (57.7)
65-74	46 (19.8)	144 (25.8)
75-84	39 (16.8)	75 (13.4)
≥ 85	4 (1.7)	17 (3.0)
Sex, male (%)	181 (78.0)	417 (74.7)	0	0.08	< 0.01
Barthel index (%)			17.3	0.10	< 0.01
100 (full activity)	83 (40.5)	186 (41.5)
1-99	63 (30.7)	152 (33.9)
0 (worst disability)	59(28.8)	110 (24.6)
Child-Pugh score, median (IQR)	8 (7-10)	8 (7-10)	12.9	0.05	0.03
Child-Pugh classification (%)			10.1	0.06	0.02
A	42 (19.4)	93 (18.8)
B	110 (50.9)	266 (53.7)
C	64 (29.6)	136 (27.5)
Presence of ascites	67 (31.0)	171 (34.5)
Comorbidities
Charlson Comorbidity Index, median (IQR)	4 (4-5)	4 (4-5)	0	< 0.01	0.01
Maintenance hemodialysis	3 (1.3)	8 (1.4)	0	0.01	< 0.01
Hepatic cancer	38 (16.4)	112 (20.1)	0	0.10	< 0.01
Malignant tumor history	29 (12.5)	65 (11.6)	0	0.03	< 0.01
Alcohol-related disease	127 (54.7)	246 (44.1)	0	0.21	< 0.01
Past varix rupture history	63 (27.2)	127 (22.8)	0	0.10	< 0.01
Medications
Antiplatelet use	3 (1.3)	8 (1.4)	0	0.01	< 0.01
Anticoagulant use	5 (2.2)	8 (1.4)	0	0.05	< 0.01
NSAIDs use	5 (2.2)	13 (2.3)	0	0.01	< 0.01
Corticosteroid use	0 (0)	2 (0.4)	0	0.09	< 0.01
Acid blocker use	214 (91.8)	486 (87.1)	0	0.15	< 0.01
β blocker use	26 (11.2)	26 (4.7)	0	0.24	< 0.01
Laboratory data
Total bilirubin, mg/dL, median (IQR)	1.6 (1-2.9)	1.4 (0.9-2.4)	3.2	0.13	0.02
Aspartate aminotransferase, U/L, median (IQR)	54.5 (32.2-94.8)	47 (31-83)	2.2	0.09	0.01
Alanine aminotransferase, U/L, median (IQR)	30.5 (20-47)	27 (19-42)	2.2	0.08	< 0.01
Albumin			4.6	0.11	0.02
> 3.5 g/dL	37 (16.5)	72 (13.6)
2.8–3.5 g/dL	97 (43.3)	256 (48.3)
< 2.8 g/dL	90 (40)	202 (38.1)
White blood cell, /μL, median (IQR)	7720 (5900-10700)	7300 (5200-10400)	1.8	0.15	0.01
Hemoglobin, g/dL, median (IQR)	9 (7.3-10.5)	8.5 (6.9-10.2)	1.8	0.12	< 0.01
Platelet, 103/μL, median (IQR)	99 (72-139)	103 (75-144)	1.8	< 0.01	0.02
C-reactive protein, mg/dL, median (IQR)	0.3 (0.1-0.7)	0.3 (0.1-0.8)	4.7	0.03	0.04
Prothrombin time			5.9	0.02	< 0.01
> 70%	48 (21.5)	113 (21.7)
40%-70%	138 (61.9)	324 (62.3)
< 40%	37 (16.6)	83 (16.0)
Activated partial thromboplastin time			11.4	0.08	0.01
≤ 40 s	185 (87.3)	436 (89.3)
40-60 s	23 (10.8)	47 (9.6)
> 60 s	4 (1.9)	5 (1.0)
eGFR < 30 mL/min/1.73 m2	19 (8.3)	40 (7.3)	1.9	0.03	< 0.01
Shock index > 1	94 (41.4)	197 (36.5)	3	0.10	< 0.01
Vasopressor use	7 (3.0)	19 (3.4)	0	0.02	< 0.01
RBC transfusion, Unit, median (IQR)	4 (0-4)	2.5 (0-4)	0	0.09	< 0.01

IPTW: Inverse probability of treatment weighting; SMD: Standardized mean difference; IQR: Interquartile range; eGFR: Glomerular filtration rate; RBC: Red blood cell.

Table 4 Antibiotic use in prophylaxis group

Antibiotic class	Number of patients
Carbapenems	4
First-Generation Cephalosporins	32
Second-Generation Cephalosporins	51
Third-Generation Cephalosporins	106
Beta-Lactamase Inhibitor Combinations	14
Macrolides	22
Lincosamides	3

Table 5 Crude and inverse probability of treatment weighting outcomes, n (%)

	Before imputation and IPTW			After imputation and IPTW
Outcomes	Prophylaxis group (n = 232)	Non-prophylaxis group (n = 558)	Odds ratio (95%CI)	Odds ratio (95%CI)	P value
Composite outcome	26 (11.2)	53 (9.5)	1.20 (0.72-1.96)	1.11 (0.61-1.99)	0.74
6-wk mortality	16 (6.9)	37 (6.6)	1.04 (0.55-1.88)	0.97 (0.47-1.98)	0.93
4-wk rebleeding	9 (3.9)	16 (2.9)	1.37 (0.57-3.08)	1.21 (0.45-3.24)	0.71
4-wk onset of SBP	5 (2.2)	10 (1.8)	1.21 (0.37-3.44)	1.20 (0.32-4.46)	0.78
In-hospital mortality	14 (6.0)	34 (6.1)	0.99 (0.50-1.84)	0.89 (0.42-1.87)	0.75
			Rate ratio (95%CI)	Rate ratio (95%CI)
Length of hospital, median (IQR)	8 (5-15)	9 (6-15)	1.01 (0.90-1.14)	1.06 (0.94-1.19)	0.34

IPTW: Inverse probability of treatment weighting; CI: Confidence interval; IQR: Interquartile range.

Table 6 Outcomes of subgroup analysis

Child-Pugh classification	Odds ratio (95%CI)	P value	P for interaction
A	0.87 (0.22–3.34)	0.84	0.32
B	0.79 (0.46–1.38)	0.41
C	1.91 (1.20–3.02)	0.01

Table 7 Outcomes of sensitivity analysis

Analysis method	Odds ratio (95%CI)	P value
IPTW	1.11 (0.61-1.99)	0.74
Propensity score matching	1.12 (0.62-2.03)	0.71
Duration of antibiotics
2 d or more	1.14 (0.59-2.20)	0.70
3 d or more	1.05 (0.50-2.21)	0.91
4 d or more	0.96 (0.43-2.18)	0.93
Third-generation cephalosporins only	1.57 (0.64-3.87)	0.33

CI: Confidence interval; IPTW: Inverse probability of treatment weighting.