Aim: Therefore, we aimed to

1. compare the efficacy of susceptibility testing guided therapy vs. empirical therapy in the third-line eradication for refractory H. pylori infection
2. assess the long-term impact of eradication therapy on the antibiotic resistance and microbiota of the gut flora and the metabolic factors.

Methods: This will be a multi-center, open labeled trial

Patients: 360 patients with failure to H. pylori eradication for at least two times will be enrolled Determination of antibiotic resistance of H. pylori:

Agar dilution test will be used to determine the minimum inhibitory concentrations of levofloxacin, tetracycline, rifabutin, and clarithromycin to guide the selection of antibiotics.

Treatment regimens and assignment: Eligible patients will be randomized to receive either one of the treatments (A) Susceptibility testing guided therapy or (B) Empirical therapy

Outcome Measurement:

Primary End Point: Eradication rate will be evaluated according to Intent-to-treat (ITT) analyses.

Secondary End Point: 1. Eradication rate according to per protocol analysis (PP analysis); 2. Frequency of adverse effects.

Inclusion criteria

• Adult (equal or greater than 20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled.