**Background:** Helicobacter pylori is a gram-negative bacterium that colonizes the gastric mucosa and can cause gastritis, peptic ulcers, atrophic gastritis, MALT lymphoma, gastric adenocarcinoma, and extra-digestive disorders such as iron deficiency anemia and chronic immune thrombocytopenic purpura. Global prevalence is approximately 50%, with higher rates in developing (50.8%) versus developed (34.7%) countries, and in adults (48.6%) compared to children (32.6%). Unlike in adults, where eradication is always recommended, pediatric international guidelines (ESPGHAN/NASPGHAN, LASPGHAN, JSPGHAN) do not recommend a 'test and treat' strategy in children. Instead, gastroscopy with antimicrobial susceptibility testing should be performed before starting eradication therapy to evaluate all possible causes of symptoms and to increase eradication rates. The prevalence of primary multidrug-resistant H. pylori infection in children is approximately 6.0%, with significantly higher rates among Asian children compared to Western children (p < 0.05).
**Methods:** The authors searched PubMed for articles published between 2018 and 2022 using terms combining (Helicobacter OR Helicobacter pylori OR H. pylori) AND (children OR pediatric) AND (treatment OR therapy OR eradication), as well as terms for probiotics, phytotherapy, synbiotics, and natural products. For treatment options, they selected randomized controlled trials, meta-analyses, guidelines, systematic reviews, and narrative/comprehensive reviews. For phytotherapy and probiotics, only reviews and meta-analyses/systematic reviews were selected due to data heterogeneity. Only English-language articles involving children or adolescents were included; non-human studies were excluded.
**Key Results:** The review summarizes multiple treatment approaches. Standard triple therapy (PPI, amoxicillin, and clarithromycin or metronidazole) for 14 days is recommended when antimicrobial susceptibility is known and all antibiotics are susceptible or only metronidazole resistance is present. In clarithromycin-resistant cases, triple therapy with PPI, amoxicillin, and metronidazole is recommended. For dual clarithromycin and metronidazole resistance, triple therapy with high-dose amoxicillin (75 mg/kg/day) and high-dose metronidazole (30-40 mg/kg/day) is recommended. Bismuth quadruple therapy is an alternative when one or two antibiotic resistances are present, with regimens differing by age (amoxicillin-based for children <8 years, tetracycline-based for children >8 years). Sequential therapy for 10-14 days showed an eradication rate of 88.7% in one study and 97.4% in another, compared to 80% for 7-day triple therapy (p = 0.032) and 83.3% for 14-day triple therapy (p = 0.07). Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole for 14 days) achieved 84.6% eradication in Chinese children, with 100% efficacy in sensitive strains but only 59% in resistant strains. Regarding probiotics, a network meta-analysis of 29 trials found that probiotics added to triple therapy significantly increased eradication rates (RR 1.19, 95% CI 1.13-1.25) and reduced side effects (RR 0.49, 95% CI 0.38-0.65). Saccharomyces boulardii supplementation improved eradication (RR 1.09, 95% CI 1.05-1.113) and reduced diarrhea (RR 0.47, 95% CI 0.36-0.61). Lactobacillus supplementation increased eradication rates (RR 1.19, 95% CI 1.07-1.33) and decreased diarrhea (RR 0.30, 95% CI 0.10-0.85). A novel bismuth-containing sequential regimen in Turkish children achieved 92% eradication. Vonoprazan-based triple therapy in Japanese junior school students achieved 85.7% eradication in per-protocol analysis. In patients with clarithromycin-resistant organisms, vonoprazan-amoxicillin dual therapy and vonoprazan triple therapy were both superior to PPI-based triple therapy (69.6% and 65.8% vs 31.9%; p < 0.001).
**Clinical Implications:** The review emphasizes that no ideal treatment regimen exists for pediatric H. pylori infection due to regional differences in drug availability and antimicrobial resistance. The best approach for achieving high eradication rates in children is susceptibility-based triple therapy for 14 days. Bismuth quadruple therapy should be reserved as second-line or rescue therapy in children, as its efficacy is not affected by antibiotic resistance. High-dose dual therapy and vonoprazan-based regimens show promise but have not been adequately studied in pediatric populations. The authors suggest that high-dose dual therapy in children could consist of omeprazole or esomeprazole at 3 mg/kg/day divided into three doses plus amoxicillin at 75 mg/kg/day divided into four doses for 14 days, though studies are needed. Probiotics may increase eradication rates by up to 10% and reduce side effects, but international guidelines do not recommend their routine addition due to low certainty of evidence. Noninvasive methods for antimicrobial susceptibility testing, such as PCR-based testing on stool samples, may facilitate tailored therapy without requiring gastroscopy. The authors conclude that tailored therapy based on antimicrobial susceptibility testing remains the best strategy, with high-dose dual therapy or vonoprazan-amoxicillin dual therapy representing the most promising future therapeutic choices.