Sayali Shelke

Introduction. Helicobacter pylori is a gram-negative bacterial infection that affects 50% of the global human population and is a topic of interest in several fields of medicine due to its severe sequalae, such as peptic ulcer, gastritis, and gastric cancer.² H. pylori possesses different virulence factors, such as flagella that reaches the protective gastric mucous layer and duodenal ulcer, maximizing the manipulation of the gastric environment.³ Triple therapy has been the standard for H. pylori treatment. It comprises a proton pump inhibitor (PPI), amoxicillin, and clarithromycin.⁶ Growing evidence indicates that clarithromycin-based therapies (CBT) are becoming increasingly ineffective for treating H. pylori infection, leading to low cure rates worldwide.³ It works by binding to the 50S bacterial ribosomal subunit of H. pylori, inhibiting protein synthesis and creating a bacteriostatic effect. Point mutations in the peptidyl transferase region of the 23s rRNA, a vital non-coding component of ribosomes, decrease the affinity of clarithromycin for the bacterial ribosome, making the drug ineffective.⁶ Rifabutin-Based Triple Therapy (RHB-105) does not contain clarithromycin, decreasing chances or resistance. Instead, RHB-105 contains rifabutin, an antibiotic that targets the DNA-binding RNA-polymerase of H. pylori, inhibiting RNA synthesis resulting in bacterial cell death.³ Specifically, rifabutin inhibits the β-subunit of H. pylori DNA-dependent RNA polymerase encoded by the rpoB gene.¹ Methods: In a phase III, double-blind clinical trial, 455 H. pylori positive patients were given RHB-105 (amoxicillin, 3 g; omeprazole, 120 mg; and rifabutin, 150 mg) versus active comparator (amoxicillin, 3 g, and omeprazole, 120 mg).² Antibiotic resistance was analyzed by using H. pylori eradication in clinical trials was analyzed via CYP2C19 status as omeprazole is metabolized by this liver enzyme. ² Results: Compared to the standard group, the experimental group that was given the Rifabutin Triple Therapy had overall lower rates of resistance. The eradication rate with RHB-105 remained high, irrespective of the resistance or susceptibility of H pylori strains causing infection.² Using CYP2C19 as a marker for eradication also showed lower rate of eradication in poor metabolizers compared to normal metabolizers in the RHB-105 group. Conclusion: Rifabutin-Based Triple Therapy should be used as standard treatment to address H. pylori infection treatment. Eradication of H. pylori infection would minimally disturb the microbiota and significantly improve patient quality of life by reducing the recurrence of peptic ulcer disease and the incidence of gastric cancer.⁵

1. Gisbert JP. Rifabutin for the Treatment of Helicobacter Pylori Infection: A Review. Pathogens. 2020 Dec 28;10(1):15. doi: 10.3390/pathogens10010015. PMID: 33379336; PMCID: PMC7823349.
2. Graham DY, Canaan Y, Maher J, Wiener G, Hulten KG, Kalfus IN. Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication: A Double-Blind, Randomized, Controlled Trial. Ann Intern Med. 2020 Jun 16;172(12):795-802. doi: 10.7326/M19-3734. Epub 2020 May 5. PMID: 32365359.
3. Howden CW, Sheldon KL, Almenoff JS, Chey WD. Pitfalls of Physician-Directed Treatment of Helicobacter pylori: Results from Two Phase 3 Clinical Trials and Real-World Prescribing Data. Dig Dis Sci. 2021 Dec 4. doi: 10.1007/s10620-021-07323-5. Epub ahead of print. PMID: 34862940.
4. Hulten KG, Lamberth LB, Kalfus IN, Graham DY. National and Regional US Antibiotic Resistance to Helicobacter pylori: Lessons From a Clinical Trial. Gastroenterology. 2021 Jul;161(1):342-344.e1. doi:10.1053/j.gastro.2021.03.045. Epub 2021 Mar 31. PMID: 33798524; PMCID: PMC8267964.
5. Kocsmár É, Buzás GM, Szirtes I, Kocsmár I, Kramer Z, Szijártó A, Fadgyas-Freyler P, Szénás K, Rugge M, Fassan M, Kiss A, Schaff Z, Röst G, Lotz G. Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides. Nat Commun. 2021 Apr 15;12(1):2255. doi: 10.1038/s41467-021-22557-7. PMID: 33859206; PMCID: PMC8050269.
6. Liou JM, Chen CC, Chang CM, Fang YJ, Bair MJ, Chen PY, Chang CY, Hsu YC, Chen MJ, Chen CC, Lee JY, Yang TH, Luo JC, Chen CY, Hsu WF, Chen YN, Wu JY, Lin JT, Lu TP, Chuang EY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial. Lancet Infect Dis. 2019 Oct;19(10):1109-1120. doi: 10.1016/S1473-3099(19)30272-5. PMID: 31559966.