Drug-Resistant Helicobacter pylori: Diagnosis and Evidence-Based Approach

Abstract

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection, affecting approximately half of the world's population. H. pylori 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 H. pylori with the likelihood of success further decreasing after each unsuccessful therapeutic effort. Antimicrobial resistance in Helicobacter pylori is a major public health concern and is a predominant cause attributed to eradication failure. As a result, determining H. pylori's antibiotic susceptibility prior to the administration of eradication regimens becomes increasingly critical. Detecting H. pylori and its antimicrobial resistance has traditionally been accomplished by time-consuming culture and phenotypic drug susceptibility testing. The resistance of H. pylori to different antibiotics is caused by various molecular mechanisms, and advances in sequencing technology have greatly facilitated the testing of antibiotic susceptibility to H. pylori. This review will summarize H. pylori 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.

Keywords: antibiotic resistance; antibiotic susceptibility testing; diagnosis; eradication failure; gastric cancer; heteroresistance; multidrug resistance; single-drug resistance; treatment failure.

Figure 1

Factors responsible for Helicobacter pylori eradication failure.

Figure 2

Decade-wise trends of antibiotic resistance among H. pylori strains (2003–2012 vs. 2013–2022) [15].

Figure 3

Region-wise data of antibiotic resistance among H. pylori strains.

Figure 4

Predominant molecular mechanisms of single-drug resistance in Helicobacter pylori.

Figure 5

Predominant mechanisms attributable to H. pylori multidrug resistance.

Figure 6

Treatment algorithm for H pylori infection. CLR: Clarithromycin, BQT: Bismuth Quadruple Therapy, HDDT: High-dose PPI-Amoxicillin dual therapy, Levofloxacin Quadruple: Bismuth plus Levofloxacin triple therapy, Rifabutin Quadruple: Rifabutin triple plus Bismuth therapy. * High-dose PPI twice daily increases the efficacy of triple therapy [1]. # Potassium-competitive acid blocker (Vonoprazan)-based dual therapy is another option when available. $ In populations with high metronidazole resistance, a high dose of metronidazole can increase the eradication rates of H. pylori infection [10].