Helicobacter pylori infection had a global prevalence of >50% and is associated with many gastrointestinal diseases, including gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma [1]. Accordingly, eradicating H. pylori could reduce the risk of the aforementioned diseases. The recommended first-line eradication therapy is the standard triple therapy (TT), using a proton pump inhibitor (PPI), amoxicillin, and clarithromycin [2]. The 2022 Maastricht VI/Florence consensus guidelines recommend bismuth quadruple therapy or clarithromycin TT as the first-line therapy for H. pylori eradication treatment when local clarithromycin resistance is below 15% [3]. Although the standard TT regimen is the regimen of choice when local clarithromycin resistance is <5%, the eradication rate is suboptimal when resistance is >15% [4]. When local resistance to clarithromycin is >15%, bismuth or non-bismuth quadruple therapy is recommended as the first-line therapy [3]. However, these two therapies with multiple antibiotics for 14 days are prone to increase antimicrobial resistance

Eradication failure of standard TT was primarily caused by antibiotic resistance, poor adherence, and rapid PPI metabolism. A multicentre report from Taiwan in 2019 demonstrated that the rates of resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, and tetracycline were 81%, 77%, 51%, 0%, and 0%, respectively [5]. The lack of amoxicillin resistance indicates that amoxicillin and PPI dual therapy could be a promising therapy.

The concept of dual therapy's antibacterial effects was introduced during the 1980s, initially exhibiting a modest eradication rate. Numerous studies have suggested that increasing the PPI dosage and frequency can achieve a high eradication rate [6]. For example, a study using high-dose and high-frequency HDDT in 2015 achieved 95.3% H. pylori eradication, suggesting the potential of high-dose and high-frequency HDDT [7]. Therefore, investigations on the H. pylori eradication rate and adverse effects of HDDT compared with the different PPIs used in this regimen are required.

Many studies have compared the eradication rates of HDDT with those of standard TT. However, the reported efficacy of HDDT varies greatly and is inconsistent. In this study, we investigated several publicly available databases, including Cochrane, EMBASE, PubMed, and Medline. We summarized the results of the current literature on the eradication and adverse event rates of HDDT compared with the latest recommended first-line therapy. We further compared the efficacy and safety of amoxicillin-containing rescue therapy with other rescue regimens.