Precision therapy guided by genotypic antibiotic resistance for Helicobacter pylori eradication: A prospective, randomized controlled trial

Table 1 Drug selection for the genotypic antibiotic susceptibility testing group

Regimen	Clarithromycin	Levofloxacin	Drugs
			Clarithromycin	Levofloxacin	Tetracycline
Cla-BQT	S	-	500 mg, bid	-	-
Lev-BQT	R	S	-	500 mg, qd	-
Tet-BQT	R	R	-	-	500 mg, tid

All regimens were administered for 14 days and included esomeprazole 20 mg twice daily, bismuth potassium citrate 220 mg twice daily, and amoxicillin 1000 mg twice daily. R: Resistant; S: Susceptible; “-” indicates this drug is not chosen; bid: Twice daily; qd: Once daily; tid: Three times daily; Cla-BQT: Clarithromycin-containing bismuth quadruple therapy; Lev-BQT: Levofloxacin-containing bismuth quadruple therapy; Tet-BQT: Tetracycline-containing bismuth quadruple therapy.

Table 2 Clinical and demographic characteristics of the studied groups, n (%)

Baseline characteristics	BQT group (n = 97)	G-AST group (n = 97)	P value	χ²/t/z
Age (years), mean ± SD	52.81 ± 10.69	50.20 ± 9.45	0.072	1.808
Gender (male)	46 (47.4)	48 (49.5)	0.083	0.774
Height (m), mean ± SD	1.67 ± 0.08	1.68 ± 0.09	0.230	-1.2
Weight (kg), mean ± SD	66.14 ± 10.56	68.24 ± 11.62	0.189	-1.318
BMI, mean ± SD	23.73 ± 2.89	24.08 ± 3.24	0.432	-0.787
Smoking	20 (20.6)	14 (14.4)	0.257	1.284
Alcohol consumption	22 (22.7)	22 (22.7)	1.0	0
Hypertension	23 (23.7)	19 (19.6)	0.486	0.486
Diabetes	22 (22.7)	13 (13.4)	0.093	2.824
Family history of gastric cancer	11 (11.3)	13 (13.4)	0.663	0.190
Bile reflux	10 (10.3)	15 (15.5)	0.284	1.148
Atrophic gastritis	63 (64.9)	52 (53.6)	0.108	2.584

BMI: Body mass index; G-AST: Genotypic antibiotic susceptibility testing; BQT: Bismuth quadruple therapy.

Table 3 Comparison of Helicobacter pylori eradication rates between the control and trial groups, n (%)

	BQT group	G-AST group	Difference in eradication rate (%)	P value	χ²
ITT	77 (79.4)	90 (92.8)	13.4	0.007	7.271
95%CI	70.3-86.2	85.8-96.5	3.7-23.2
PP	74 (84.1)	90 (97.8)	13.7	0.001	10.477
95%CI	75.1-90.3	92.4-99.4	5.5-23.0

Bismuth quadruple therapy group received esomeprazole 20 mg twice daily + bismuth potassium citrate 220 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily; genotypic antibiotic susceptibility testing group received esomeprazole 20 mg twice daily + bismuth potassium citrate 220 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily/Levofloxacin 500 mg once daily/tetracycline 500 mg three times daily. G-AST: Genotypic antibiotic susceptibility testing; ITT: Intention-to-treat analysis; PP: Per-protocol analysis; BQT: Bismuth quadruple therapy.

Table 4 Subgroup analysis of the trial group

G-AST group	Eradication rate, n/N [% (95%CI)]
	ITT	PP
Overall eradication rates	90/97 [92.8 (85.8-96.5)]	90/92 [97.8 (92.4-99.4)]
Cla-BQT	55/60 [91.7 (81.9-96.4)]	55/56 [98.2 (90.6-99.7)]
Lev-BQT	18/19 [94.7 (75.4-99.1)]	18/19 [94.7 (75.4-99.1)]
Tet-BQT	17/18 [94.4 (74.2-99.0)]	17/17 [100 (81.6-100.0)]
P value	0.863	0.530
χ²	0.294	1.270

Genotypic antibiotic susceptibility testing group received esomeprazole 20 mg twice daily + bismuth potassium citrate 220 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily/Levofloxacin 500 mg once daily/tetracycline 500 mg three times daily. G-AST: Genotypic antibiotic susceptibility testing; ITT: Intention-to-treat analysis; PP: Per-protocol analysis; Cla-BQT: Clarithromycin-containing bismuth quadruple therapy; Lev-BQT: Levofloxacin-containing bismuth quadruple therapy; Tet-BQT: Tetracycline-containing bismuth quadruple therapy.

Table 5 Helicobacter pylori resistance rate, n (%)

Antibiotics	Susceptible	Resistant
Clarithromycin	60 (61.9)	37 (38.1)
Levofloxacin	58 (59.8)	39 (40.2)
Clarithromycin and levofloxacin	38 (39.2)	17 (17.5)

Table 6 Adverse events and patient compliance, n (%)

Adverse events	BQT group (n = 97)	G-AST group (n = 97)	P value
Bitter taste	9 (9.3)	7 (7.2)
Nausea	5 (5.2)	4 (4.1)
Abdominal pain	3 (3.1)	4 (4.1)
Diarrhea	4 (4.1)	3 (3.1)
Abdominal discomfort	2 (2.1)	2 (2.1)
Bloating	1 (1.0)	3 (3.1)
Heartburn	1 (1.0)	2 (2.1)
Skin rash	1 (1.0)	2 (2.1)
Dizziness	2 (2.1)	3 (3.1)
Total	28/97 (28.9)	30/97 (30.9)	0.754

Bismuth quadruple therapy group received esomeprazole 20 mg twice daily + bismuth potassium citrate 220 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily; genotypic antibiotic susceptibility testing group received esomeprazole 20 mg twice daily + bismuth potassium citrate 220 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily/Levofloxacin 500 mg once daily/ tetracycline 500 mg three times daily. G-AST: Genotypic antibiotic susceptibility testing; BQT: Bismuth quadruple therapy.