Antibiotic susceptibility, heteroresistance, and updated treatment strategies in <em>Helicobacter pylori</em> infection

Abstract

In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.

Molecular diagnosis of Helicobacter pylori infection in gastric biopsies: Evaluation of the Amplidiag®H. pylori + ClariR assay

“…The rate of detected mixed population ranged from 4.4% to 71% depending on the study. 21,27,28 We report here a rate of mixed population of 9.6% with different mutations or a mixed susceptible-resistant genotype. Different strains coexisting in the same biopsy (the presence of two populations of H. pylori) or mutated and wild-type alleles (different 23S ribosomal DNA alleles) present in the same strain could not be determined.…”

“…Heteroresistance is defined as the coexistence of susceptible and resistant isolates in the same patient for the same antimicrobial agent. The rate of detected mixed population ranged from 4.4% to 71% depending on the study . We report here a rate of mixed population of 9.6% with different mutations or a mixed susceptible‐resistant genotype.…”

“…[15][16][17] Unfortunately, primary clarithromycin resistance is increasing worldwide and has been considered a main factor for failure of H. pylori eradication therapy. [21][22][23] Recently, Graham stated that the most important point is to ensure that the organism is susceptible to the antibiotics used. 24 As previously described, mutations A2143G and A2142G were largely predominant, representing 89% of mutations.…”

Evaluation of the Direct Economic Cost per Eradication Treatment Regimen against Helicobacter pylori Infection in Greece: Do National Health Policy-Makers Need to Care?

“…High antibiotic resistance has provoked a gradual escalation of eradication treatment regimens, following an "add-on" strategy, especially in regions such as in Greece where bismuth containing medications are not commercially available [18,24,25]. Hp resistance to clarithromycin (>20%) has been recognized as the most determinant hindrance of eradication treatment success [26] and in that setting, quadruple regimens are indicated [10,27].…”

Probiotics improved the effectiveness and safety of the quadruple Helicobacter pylori eradication therapy

“…The overall prevalence of Hp infection remained high and it can reach as high as 60% in China. In recent years, with the application of antibiotics in the eradication of Hp, drug resistance and micro-environmental changes could cause the ineffectiveness of the regimen and the increase of the adverse events [9]. Probiotics can benefit the human healthy by regulating the immune function and medicating the normal functional activities, especially in the gastrointestinal tract [10].…”