Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

Abstract

Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

Coating Nanoparticles with Gastric Epithelial Cell Membrane for Targeted Antibiotic Delivery against Helicobacter pylori Infection

“…[6, 7] Alternative agents and treatment regimens to address resistance development are being actively studied, but the results remain mixed. [8, 9] Clearly, new and effective anti- H. pylori treatments are urgently needed.…”

Short‐ and long‐term evolution in our arms race with cancer: Why the war on cancer is winnable

“…Second, combinatorial therapies are increasingly recognized as our most powerful means of preventing cancer cells from evolving resistance (Hanahan, ; Kaiser, ; Loeb, ; Lopez & Banerji, ). In fact, combinatorial strategies appear to retard resistance evolution in diverse settings where resistance evolution is an especially acute concern (Goldberg et al., ; Zur Wiesch, Kouyos, Engelstädter, Regoes, & Bonhoeffer, ): Drug cocktails have provided a means of coping with drug‐resistant bacterial and viral pathogens (e.g., Mycobacterium tuberculosis , Gandhi et al., ; H. pylori , Hu, Zhu, & Lu, ; HIV, Arts & Hazuda, ), and toxin combinations can effectively slow resistance evolution in insect herbivores feeding on transgenic crop plants (Carrière, Fabrick, & Tabashnik, ). Resistance evolution against vaccines appears to be rare largely because vaccines induce immune responses against multiple therapeutic targets on the pathogen simultaneously, thus generating the multiple redundant pathways to pathogen killing that are at the heart of the combination strategy (Kennedy & Read, ).…”

“…If the anticancer interventions involve treatments directed against the pathogens themselves, then we face the full power of a continuous evolutionary process favoring resistance evolution. For example, antibiotic treatments for H. pylori are a standard treatment for gastric cancers, and not surprisingly resistant H. pylori are a growing clinical concern (Hu et al., ). If, however, we treat the cancer itself, for instance with cytotoxic agents or targeted chemotherapies, then our interests often do not conflict with the evolutionary interests of the pathogen, and thus, we should not expect pathogen evolution to oppose our cancer treatments.…”

The effect of antioxidants on Helicobacter pylori eradication: A systematic review with meta‐analysis

“…10,11 Resistance to antibiotics, patient compliance, massive gastric bacterial loads, internalizing bacteria, and biofilm formation may account for the failure of H. pylori eradication. 13 Antioxidants (eg, vitamins and N-acetylcysteine) are involved in reducing reactive oxygen species and gastric inflammations induced by H. pylori, 14 inhibiting bacterial growth 15 and destroying biofilm formation. 13 Antioxidants (eg, vitamins and N-acetylcysteine) are involved in reducing reactive oxygen species and gastric inflammations induced by H. pylori, 14 inhibiting bacterial growth 15 and destroying biofilm formation.…”

“…12 Therefore, it is critical to identify an effective regimen in this era of increasing antibiotic resistance. 13 Antioxidants (eg, vitamins and N-acetylcysteine) are involved in reducing reactive oxygen species and gastric inflammations induced by H. pylori, 14 inhibiting bacterial growth 15 and destroying biofilm formation. 16 Numerous studies have indicated that vitamins C and E levels are lower in subjects with H. pylori than in those without H. pylori.…”