Current potential for Helicobacter pylori triple pharmacotherapy

Helicobacter pylori infection represents a global public health problem, as the pathogen is associated with the development of gastric and duodenal ulcer disease, gastritis, gastric adenocarcinoma, and MALT lymphoma. The efficacy of eradication therapy is declining due to increasing antibiotic resistance, necessitating a revision of therapeutic strategies. The article presents the mechanisms of H. pylori survival in the aggressive gastric environment, its pathogenicity factors, current data on the mechanisms of action of the main antibacterial drugs used for treating the infection in Russia and worldwide: clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, rifabutin, bismuth tripotassium dicitrate, as well as the mechanisms of resistance development for these agents. Single-phase and two-phase eradication therapy regimens are examined in detail according to the 2022 Russian clinical guidelines and the Maastricht VI consensus, including first-line regimens: standard triple therapy, bismuth-enhanced and non-bismuth-enhanced, concomitant, sequential, hybrid, reverse hybrid, bismuth-based quadruple therapy, high-dose dual therapy, and vonoprazan-based dual therapy. For second-line therapy, regimens including levofloxacin and rifabutin are reviewed, and the principles of individualized therapy are outlined. A brief clinical and pharmacological characterization of each drug is provided. The reasons for failures in finding the optimal H. pylori eradication regimen are also analyzed. The World Health Organization's changing stance toward H. pylori as a pathogen requiring the development of new antibacterial drugs is mentioned. The concepts of the "post-antibiotic era" and the renaissance of antibiotics are discussed. The concluding section examines the risks associated with the choice of first-line therapy regimens and the drugs included in them. It is concluded that with proper assessment of H. pylori resistance, triple pharmacotherapy with or without bismuth is a relatively effective and safe eradication regimen for regions of the Russian Federation. Consideration of clarithromycin metabolism characteristics and adverse drug reactions allows for rational selection of first-line therapy that accounts for the physiological and clinical features of patients with H. pylori infection.