Eradication Treatment of Helicobacter pylori Infection Based on Molecular Pathologic Antibiotic Resistance

Figures & data

Table 1 Patients’ Demographics

Characteristic Data	All Patients * (n=261)	First-Treated Patients* (n=111)	Re-Treatment Patients* (n=150)	P value
Mean age, mean ± SD, years	52.3 ± 15.4	53.9 ± 16.9	51.1 ± 14.2	0.159
Gender, no. (%)				<0.001
Male	116 (44.4)	64 (57.7)	52 (34.7)
Female	145 (55.6)	47 (42.3)	98 (65.3)
Endoscopic findings, no. (%)
Chronic superficial gastritis	146 (55.9)	56 (50.5)	90 (60.0)	0.124
Chronic atrophic gastritis	115 (44.1)	55 (49.5)	60 (40.0)	—
Duodenal ulcer	34 (13.0)	16 (14.4)	18 (12.0)	0.567
Gastric ulcer	8 (3.1)	4 (3.6)	4 (2.7)	0.943
Diagnosis of Infection before treatment, no. (%)
Pathology	261 (100)	111 (100)	150 (100)	—
Diagnosis of Infection after treatment, no. (%)
UBT (^13C-urea breath test)	239 (91.6)	104 (93.7)	135 (90.0)	0.288
Pathology	30 (11.5)	7 (6.3)	23 (15.3)	0.024
CYP2C19 genotypes^a, no. (%)				0.150
Rapid metabolizer (RM)	108 (45.6)	51 (53.1)	57 (40.4)
Intermediate metabolizer (IM)	105 (44.3)	36 (37.5)	69 (48.9)
Poor metabolizer (PM)	24 (10.1)	9 (9.4)	15 (10.6)
Lost to follow up, no. (%)	6 (2.3)	3 (2.7)	3 (2.0)	1.000

Notes: *A total of 261 patients were retrospectively analyzed, including 111 patients who were treated for the first time (one group as First-treated) and 150 patients who failed at least once in bismuth quadruple therapy (another group as Re-treatment). ^aData were available in 237 patients, including 96 in first-treated and 141 in re-treated patients.

Figure 1 Flow diagram of this study.

Table 2 Antibiotic Resistance of H. pylori: Molecular Pathologic Results

Resistance to Antibiotic	Mutation Sites	All Patients* (n=261)	First-Treated Patients* (n=111)	Re-Treatment Patients* (n=150)	P value
Amoxicillin (A)^a, no. (%)	PBP1	23 (9.0)	6 (5.5)	17 (11.7)	0.083
Clarithromycin (C)^b, no. (%)	23S rRNA	159 (63.6)	45 (42.1)	114 (79.7)	<0.001
Fluoroquinolone (F)^c, no. (%)	gyrA	151 (58.5)	45 (41.7)	106 (70.7)	<0.001
Tetracycline (T)^d, no. (%)	16S rRNA	49 (22.2)	13 (12.9)	36 (30.0)	0.002
AMPC + CAM^e, no. (%)		14 (5.7)	5 (4.7)	9 (6.4)	0.566
AMPC + FLQ^f, no. (%)		13 (5.2)	3 (2.8)	10 (6.9)	0.147
AMPC + TET^g, no. (%)		10 (4.6)	3 (3.0)	7 (5.9)	0.470
CAM + FLQ^h, no. (%)		109 (44.1)	26 (25.0)	83 (58.0)	<0.001
CAM + TET^i, no. (%)		39 (17.8)	10 (9.9)	29 (24.6)	0.005
FLQ + TET^j, no. (%)		34 (15.5)	8 (8.1)	26 (21.7)	0.006
≥ 3 (A/C/F/T), no. (%)		43 (16.5)	12 (10.8)	31 (20.7)	0.034

Notes: *A total of 261 patients were retrospectively analyzed, including 111 patients who were treated for the first time (one group as First-treated) and 150 patients who failed at least once in bismuth quadruple therapy (another group as Re-treatment). Data were available in ^a255 (110+145), ^b250 (107+143), ^c258 (108+150), ^d221 (101+120), ^e246 (106+140), ^f252 (107+145), ^g219 (101+118), ^h247 (104+143), ⁱ219 (101+118), and ^j219 (99+120) patients. The numbers before the brackets indicate the total available cases in the two groups.

Abbreviations: AMPC (A), amoxicillin; CAM (C), clarithromycin; FLQ (F), fluoroquinolone; TET (T), tetracycline.

Figure 2 The prevalence of antibiotic resistance determined by molecular pathologic tests. The gray histogram indicates the percentage of antibiotic resistance in first-treated patients who were treated for the first time, and the black histogram indicates the percentage in re-treatment patients who failed in bismuth quadruple therapy. As demonstrated, the resistance rates to amoxicillin, clarithromycin, fluoroquinolone and tetracycline were 5.5%, 42.1%, 41.7% and 12.9%, in first-treated patients, whereas 11.7%, 79.7%, 70.7% and 30.0%, respectively, in re-treatment patients.

Table 3 Treatment Regimen of H. pylori Eradication

Eradication Regimen^＃	All Patients* (n=254)	First-Treated Patients (n=108)	Re-Treatment Patients (n=146)	P value
AMPC + CAM, no. (%)	59 (23.2)	40 (37.0)	19 (13.0)	<0.001
AMPC + FLQ, no. (%)	65 (25.6)	36 (33.3)	29 (19.9)	0.015
AMPC + TET, no. (%)	62 (24.4)	15 (13.9)	47 (32.2)	0.001
AMPC + FZD, no. (%)	43 (16.9)	11 (10.2)	32 (21.9)	0.014
Other regimens^§, no. (%)	25 (9.8)	6 (5.6)	19 (13.0)	0.049

Notes: *Two hundred and sixty-one patients were retrospectively analyzed and 7 patients had not been treated by any regimen because 6 patients were resistant to all available antibiotics and one patient was intractable. ^＃For all patients, whether they were treated for the first time or re-treated, bismuth quadruple therapy was used and the two antibiotics were shown in this Table. ^§Twenty-five patients were treated by other regimens, including CAM + FLQ for 5 patients, CAM + FZD for 2 patients, CAM + TET for 2 patients, FLQ + FZD for 7 patients, FLQ + TET for 5 patients, and FZD + TET for 4 patients.

Abbreviations: AMPC, amoxicillin; CAM, clarithromycin; FLQ, fluoroquinolone; FZD, Furazolidone; TET, tetracycline.

Figure 3 Eradication rates of H. pylori based on molecular pathologic antibiotic resistance. The gray and black histograms indicate the eradication rates in first-treated and re-treatment patients.

Abbreviations: ITT, intention-to-treat analysis; PP, per-protocol analysis.

Table 4 Safety and Comparison of Adverse Events

Adverse Event	All Patients* (n=254)	First-Treated Patients (n=108)	Re-Treatment Patients (n=146)	P value
Diarrhea, no. (%)	11 (4.3)	6 (5.6)	5 (3.4)	0.608
Black stool, no. (%)	246 (96.9)	105 (97.2)	141 (96.6)	1.000
Nausea/Vomiting, no. (%)	8 (3.1)	5 (4.6)	3 (2.1)	0.425
Abdominal pain, no. (%)	9 (3.5)	4 (3.7)	5 (3.4)	1.000
Flatulence, no. (%)	4 (1.6)	2 (1.9)	2 (1.4)	1.000
Belching, no. (%)	5 (2.0)	2 (1.9)	3 (2.1)	1.000
Heart burn, no. (%)	7 (2.8)	3 (2.8)	4 (2.7)	1.000
Skin rash, no. (%)	3 (1.2)	1 (0.9)	2 (1.4)	1.000
Headache, no. (%)	7 (2.8)	4 (3.7)	3 (2.1)	0.685
Dysgeusia, no. (%)	68 (26.8)	43 (39.8)	25 (17.1)	<0.001
Fever, no. (%)	4 (1.6)	2 (1.9)	2 (1.4)	1.000
Constipation, no. (%)	4 (1.6)	1 (0.9)	3 (2.1)	0.838
Anorexia, no. (%)	5 (2.0)	3 (2.8)	2 (1.4)	0.733
Fatigue, no. (%)	6 (2.4)	2 (1.9)	4 (2.7)	0.966
Dizziness, no. (%)	6 (2.4)	3 (2.8)	3 (2.1)	1.000

Notes: *Two hundred and sixty-one patients were retrospectively analyzed and 7 patients had not been treated by any regimen because 6 patients were resistant to all available antibiotics and one patient was intractable.