Helicobacter pylori infects nearly half the world’s population and is a major cause of chronic gastritis, peptic ulcers, MALT lymphoma, and gastric cancer.

Despite decades of research and treatment advances, the eradication of this bacterium is increasingly complicated by rising antimicrobial resistance and bacterial biofilm formation.

Updated Diagnostic and Eradication Indications

Current global consensus strongly recommends the use of the urea breath test as the diagnostic gold standard owing to its accuracy and non-invasive nature.

Clinical indications for eradication have expanded, with most guidelines advocating treatment upon confirmed infection regardless of symptomatology, especially for patients on prolonged non-steroidal anti-inflammatory drugs or aspirin, those with active peptic ulcers, and patients diagnosed with gastric MALT lymphoma.

Evolving First-Line and Second-Line Treatment Regimens

The established standard of care now favors bismuth quadruple therapy (BQT)—comprising a proton pump inhibitor (PPI), bismuth, and two antibiotics—as the preferred first-line treatment for both treatment-naïve and treatment-experienced patients due to its higher efficacy in overcoming antibiotic resistance.

Emerging data have highlighted that high-dose dual therapy (involving amoxicillin and a PPI) offers comparable effectiveness and safety profiles, providing a valuable alternative where bismuth availability or tolerance is a concern. Second-line treatments prioritize levofloxacin-based triple therapy or rifabutin-based regimens which are gaining traction amid clarithromycin and metronidazole resistance escalation.

Inovative Strategies Beyond Conventional Antibiotics

Given the adaptive nature of H. pylori, research is pivoting toward novel adjunct therapies to overcome resistance. Approaches such as targeting bacterial biofilms, employing phage therapy, utilizing probiotics to restore gastric microbial balance, and developing nanoparticle delivery systems for antimicrobials represent promising frontiers.

Importance of Personalized and Regionalized Treatment Approaches

Variability in antibiotic resistance patterns among different geographic regions necessitates incorporation of local antimicrobial susceptibility testing and patient antibiotic history into treatment selection to optimize outcomes.

Where culture and susceptibility testing are unavailable, empirical BQT remains the cornerstone of therapy, however, greater emphasis is placed on developing robust national or regional resistance surveillance systems to inform clinical decisions.

Renowned gastroenterologist Dr. James R. Goldenring, a specialist in H. pylori pathogenesis, states, "The increasing challenges posed by antibiotic resistance in H. pylori demand a rigorous, evidence-based approach emphasizing combination regimens and novel adjuncts to achieve durable infection clearance."

Another expert, Dr. David Y. Graham, a pioneer in H. pylori research, emphasizes, "Successful eradication hinges on tailoring therapy based on regional resistance patterns and ensuring adherence to multifaceted regimens, as standardized one-size-fits-all therapies are increasingly inadequate."

The management of H. pylori infection continues to evolve in response to growing antimicrobial resistance and diagnostic advancements. Contemporary protocols endorse bismuth quadruple therapy as the preferred initial treatment supplemented by high-dose dual therapy and newer agents like rifabutin or vonoprazan-based regimens in refractory cases.

Integrating diagnostic precision, personalized antimicrobial selection, and exploration of non-antibiotic therapeutic adjuncts will be paramount in achieving sustained eradication and reducing the global burden of H. pylori-related diseases.