Role of Vonoprazan-Amoxicillin Dual Therapy in Pediatric Refractory Helicobacter Pylori Infection in Children: Early Experience From A Single-Center Case Series

ABSTRACT

This small case series presents real-world experience on the efficacy of dual therapy with vonoprazan and amoxicillin in pediatric patients with refractory, antimicrobial-resistant Helicobacter pylori infection and highlights the role of adequate acid suppression in treatment success. Dual therapy with vonoprazan and amoxicillin was well tolerated and resulted in successful eradication in all patients.

INTRODUCTION

Acid suppression plays a pivotal role in the treatment of Helicobacter pylori (HP) infection, as it influences both bacterial replication and antibiotic bioavailability.^1,2 Potassium-competitive acid blockers (P-CABs) provide faster and more sustained acid suppression compared with proton-pump inhibitors (PPIs). In adults, P-CAB-based treatment regimens are superior, or at least noninferior, to conventional PPI-based triple therapies and are more effective in patients with antimicrobial-resistant infections.^3–5 Data on children are mostly limited to Asian populations,^6–10 with scarce information on US children.

METHODS

We reviewed records of patients under the care of a single physician at Boston Children's Hospital in Boston, MA, from January 2024 to March 2025, with refractory HP infection who had failed at least 1 prior eradication treatment despite reported adequate compliance (>90%) with guideline-recommended per-kilogram dosing and frequency of both PPIs and antibiotics. HP was diagnosed by both positive histology and culture. Patients were treated with vonoprazan 20 mg twice daily (BID) plus amoxicillin 1,000 mg 3 times daily (TID) for 14 days. Vonoprazan dosing was based on prior pediatric studies,^6–10 while amoxicillin dosing followed pediatric guidelines for TID dosing.¹¹ These choices also facilitated the use of formulations currently available in the United States.¹² We collected demographic data, HP treatment, antimicrobial susceptibility, endoscopic and histologic findings, eradication results, and reported side effects.

RESULTS

Eleven patients were included (mean age 14.4 ± 3.4 years; 91% male; 45% Hispanic; race: 45% White, 27% Asian, 18% Black, 9% other). The mean baseline weight was 61.6 kg (range 30–87.1), height 164.2 cm (132.5–187.2), and body mass index (BMI) z-score 0.55 (–2.24 to 2.17); follow-up BMI z-score (2–15 months, median 4) was 0.46 (–2.72 to 2.17). Endoscopy indications: epigastric pain 45%, dysphagia 27%, and dyspepsia/melena/anemia 9% each. Six had chronic gastrointestinal disease (5 EoE, 1 inflammatory bowel disease [IBD]). Endoscopic findings: nodular antrum 73%, duodenal erosion/ulcer 18%, gastric ulcer 9%, duodenitis 9%, and normal 9%. Histology showed chronic gastritis in all, active in 7, inactive in 4 (Table 1).

Table 1.

Clinical summary of patients with refractory H. pylori infection treated with vonoprazan + amoxicillin dual therapy

Case	Age/sex. Race/ethnicity. Indication for EGD	Endoscopic findings	Histologic findings	Empiric therapy	Culture +	Prior H. pylori regimens post-EGD (sequentially, before vonoprazan dual)a	Eradication test	Eradication success	Vonoprazan + amoxicillin regimen side effects
1	8M, White Dysphagia, epigastric pain, EoE	• Nodular antrum	• Chronic active gastritis	CBT	Yes	I. MET triple II. Esomeprazole + high dose amoxicillin	Stool antigen	Yes	Diarrhea
2	17M, Black Follow-up of EoE and history of H. pylori infection	• Esophagitis • Gastric ulcer • Duodenitis	• Esophagitis • Chronic active gastritis	CBT	Yes	I. BQT II. LEV triple	Stool antigen	Yes	None
3	13M, Asian Dyspepsia	• Nodular antrum	• Chronic active gastritis	MET triple	Yes	None	Stool antigen	Yes	None
4	15M, White/Hispanic. Chronic H. pylori gastritis, anemia	• Normal	• Chronic active gastritis	CBT	Yes	I. BQT II. LEV triple	Stool antigen	Yes	None
5	18M, Black Epigastric pain and history of IBD	• Antral erythema	• Chronic inactive gastritis	CBT	No	I. BQT	Stool antigen	Yes	None
6	16M, White/Hispanic. Follow-up of EoE and history of H. pylori infection	• Esophagitis • Nodular antrum	• Esophagitis • Chronic inactive gastritis	None	Yes	I. CBT II. BQT	EGD with biopsy and culture	Yes	None
7	10M, White/Hispanic. follow-up of EoE and history of H. pylori infection	• Nodular antrum	• Chronic inactive gastritis	None	Yes	I. BQT II. Esomeprazole + high dose amoxicillin	EGD with biopsy and culture	Yes	Nausea
8	18M, other/Hispanic. Epigastric pain and positive stool antigen test	• Nodular antrum • Antral erythema	• Chronic inactive gastritis	None	No	I. MET triple	Stool antigen	Yes	None
9	12M, Asian Dysphagia, melena and history of H. pylori infection and EoE	• Esophagitis • Nodular antrum • Duodenal erosion	• Esophagitis • Chronic active gastritis • Duodenitis	CBT	Yes	I. MET triple	Stool antigen	Yes	None
10	13M, White/Hispanic. Epigastric pain and history of H. pylori infection treated	• Nodular antrum	• Chronic active gastritis	CBT	Yes	I. MET triple II. BQT	Stool antigen	Yes	None
11	18F Asian Dysphagia and epigastric pain	• Nodular antrum	• Chronic active gastritis	MET triple	No	None	Stool antigen	Yes	None

BQT, PPI + bismuth + metronidazole + tetracycline; CBT, clarithromycin-based triple therapy; EGD, esophagogastroduodenoscopy; EoE, eosinophilic esophagitis; IBD, inflammatory bowel disease; MET/LEV triple = metronidazole/levofloxacin + amoxicillin + PPI.

^a All prior therapies listed represent treatment failures before initiating vonoprazan + amoxicillin.

Eight patients (73%) were empirically treated by the referring primary care provider, usually with clarithromycin-based triple therapy (CBT); only 2 received guideline-concordant metronidazole, amoxicillin, and PPI (MBT). Culture growth and susceptibility were available in 8 of 11 patients (Table 2). Post-esophagogastroduodenoscopy first-line regimens: MBT (36%), bismuth quadruple therapy (BQT) with tetracycline (45%), and clarithromycin-based triple therapy (18%). Second-line regimens: BQT with tetracycline (18%), levofloxacin-based triple therapy (18%), and high-dose PPI-amoxicillin dual therapy (18%) (Table 1).

Table 2.

Antibiotic susceptibility profiles of culture-positive H. pylori cases

Antibiotic	Case 1	Case 2	Case 3	Case 4	Case 6	Case 7	Case 9	Case 10
Clarithromycin	S	S	R	R	S	R	R	S
Levofloxacin	S	S	S	R	S	S	S	R
Metronidazole	S	R	R	R	S	R	R	R

S, sensible; R, resistant.

Vonoprazan-amoxicillin dual therapy was used as second-line in 2 patients, third-line in 3, and fourth-line in 6. It was well tolerated; 18% reported mild side effects (nausea 9%, diarrhea 9%). Test of cure at 6–8 weeks (82% stool antigen, 18% endoscopy/culture) confirmed eradication in all patients.

DISCUSSION

In this small series of pediatric patients with refractory, antimicrobial-resistant HP infections, we present novel data on the efficacy of dual therapy with vonoprazan and amoxicillin, which was well tolerated and achieved successful eradication in all patients.

HP eradication is influenced by multiple factors, including bacterial (virulence, antimicrobial resistance), host (genetics, adherence), and treatment (drug, dose, duration).^13–15 In a prior US pediatric cohort, weight-based PPIs and amoxicillin dosing affected HP eradication.¹⁶ Recently revised pediatric clinical guidelines highlighted the importance of adequate PPI dosing and optimized amoxicillin dosing.¹¹

The effectiveness of PPIs is limited by the need for enteric coating, dosing before meals, and the impact of CYP2C19 rapid metabolizer genetic polymorphism.¹⁷ P-CABs such as vonoprazan offer faster and more sustained acid suppression compared with PPIs and have been extensively studied in Asian populations,¹⁸ and to a lesser extent in Europe¹⁹ and United States²⁰ Vonoprazan was approved by the FDA in 2024 for use in combination with amoxicillin alone or with amoxicillin and clarithromycin.¹² The 2022 Maastricht VI/Florence Consensus,⁴ the 2024 American Gastroenterological Association Clinical Practice Update,³ and American College of Gastroenterology-HP clinical guidelines⁵ now also recommend the use of P-CABs over PPIs as first-line therapy for most patients with HP infection, particularly in subpopulations with clarithromycin resistance.

Data in children are scarce and, as in adults, are derived primarily from Asian populations, specifically Japan.^6–10 Eradication rates for first-line vonoprazan-based triple therapies range from 81.3% to 82.6% (ITT) and 83.8% to 85.7% (PP). Only 1 prospective study of 60 adolescents evaluated first-line vonoprazan-amoxicillin dual therapy (20 mg vonoprazan, 750 mg amoxicillin BID), reporting eradication rates of 85.0% (ITT) and 86.4% (PP).¹⁰ The ≥90% eradication rate recommended by pediatric guidelines was not achieved, suggesting that further optimization may be necessary, such as higher amoxicillin doses, as used in our cohort. Three studies reported second-line therapy eradication rates all above 90%.^6–8 Likewise, our cohort demonstrated similarly high eradication rates for second, third, and fourth-line regimens. Adverse event rates range from 4% to 21%,^7–10 with a higher rate of 36.9% observed with patient self-reporting.⁶ The main adverse events include gastrointestinal symptoms such as diarrhea, nausea, and abdominal pain. No child-specific adverse events or serious outcomes have been reported. Adverse events were rare in our series; the only patient <35 kg developed diarrhea, suggesting the need for dose adjustment or shorter duration in smaller children. Mean BMI z-scores at baseline and median 4-month follow-up indicated stable growth.

In our cohort, 45% had EoE and 9% IBD. Possible reasons for treatment failure in patients with EoE include difficulty swallowing medication, which may affect adherence to regimens involving multiple tablets, such as BQT. The vonoprazan tablet is small and easy to swallow, offering a particular advantage for these patients. Similar challenges may arise for patients with IBD, including poor tolerance of multiple medications and microbiota alterations, leading to nonadherence to empiric regimens.

The study's retrospective, uncontrolled design, inherent to a case series, limits our conclusions. The vonoprazan dose used was consistent with adult regimens and based on prior adolescent studies but lacked pediatric pharmacokinetic justification. Furthermore, the lack of systematic growth and development monitoring is an important limitation, highlighting the need for pediatric pharmacokinetic and long-term safety studies. Large multicenter studies with comparison with standard second-line therapies are needed to determine whether the observed efficacy is superior to existing treatments, particularly in pediatric patients with antimicrobial-resistant infections.

DISCLOSURES

Author contributions: MCC Fernandez: Review and editing of the manuscript draft. KR Arellanos: Data analysis, figure construction, and review and editing of the manuscript draft. S. Bonilla: Conceptualization, data collection, project supervision, and drafting of the initial manuscript. All authors reviewed and approved the final version of the manuscript.

Silvana Bonilla accepts full responsibility for the conduct of the study, the integrity of the data, and the accuracy of the case report.

Financial disclosure: None to report.

Previous presentation: This case was submitted as an abstract for consideration for the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Annual Meeting, to be held in Chicago in November 2025.

Informed consent was obtained for this case report.

ABBREVIATIONS:

BID

twice daily

BMI

body mass index

BQT

bismuth quadruple therapy

CBT

clarithromycin-based triple therapy

EGD

esophagogastroduodenoscopy

EoE

eosinophilic esophagitis

HP

helicobacter pylori

IBD

inflammatory bowel disease

MBT

metronidazole-based triple therapy

MET

metronidazole

P-CABs

potassium competitive acid blockers

PCP

primary care provider

PPI

proton pump inhibitor

TID

3 times daily