| Summary: | <i>Helicobacter pylori</i> (<i>H. pylori</i>) is the most common chronic bacterial infection, affecting approximately half of the world’s population. <i>H. pylori</i> is a Class I carcinogen according to the World Health Organization, and the International Agency for Research on Cancer (IARC) has linked it to 90% of stomach cancer cases worldwide. The overall pattern points to a yearly reduction in eradication rates of <i>H. pylori</i> with the likelihood of success further decreasing after each unsuccessful therapeutic effort. Antimicrobial resistance in <i>Helicobacter pylori</i> is a major public health concern and is a predominant cause attributed to eradication failure. As a result, determining <i>H. pylori</i>’s antibiotic susceptibility prior to the administration of eradication regimens becomes increasingly critical. Detecting <i>H. pylori</i> and its antimicrobial resistance has traditionally been accomplished by time-consuming culture and phenotypic drug susceptibility testing. The resistance of <i>H. pylori</i> to different antibiotics is caused by various molecular mechanisms, and advances in sequencing technology have greatly facilitated the testing of antibiotic susceptibility to <i>H. pylori</i>. This review will summarize <i>H. pylori</i> antibiotic resistance patterns, mechanisms, and clinical implications. We will also review the pros and cons of current antibiotic susceptibility testing methods. Along with a comparison of tailored susceptibility-guided regimens and empirical therapy based on the latest evidence, an evidence-based approach to such situations will be explored.
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