Overcoming antibiotic-resistant Helicobacter pylori infection: Current challenges and emerging approaches

Table 3 Overview of current treatments, potential approaches, and future directions in overcoming antibiotic resistance in Helicobacter pylori

	AST-guided therapy		Empirical therapy						Antibiofilm agents	Probiotics
	By phenotypic determination	By molecular determination	BQT	Non-BQT	CLA-TT	LEV-TT or LEV-QT	AMX-DT	RIF-TT
Advantages	Antimicrobial stewardship; AST can be done for all recommended antibiotics (vs molecular-AST)	Antimicrobial stewardship; reliable to detect CLA resistance; does not require the isolation of viable species; non-inferior efficacy vs BQT; less cost vs non-BQT in some RCTs	Optimal reliability (> 90% cure rate) regardless of resistance profile in Europe and some Latin American countries	Possible option when bismuth is not available	Reduced costs; fewer antibiotics	In second-line therapy, LEV-QT is comparable to BQT in areas with increased trends in resistance	Good reliability in general	Good reliability in general	May improve eradication rates in biofilm-forming multidrug-resistant strains	May improve eradication rates and lower the risk of side effects
Limitations	Highly time-consuming; affected by collection, transport, and techniques; availability	Limited number of antimicrobial agents; limited correlation with MET resistance; availability	Complex dosing in conventional regimens; availability	Not indicated in regions with dual resistance > 15%	Indicated only if CLA resistance < 15% in updated data	High trends in resistance compromise LEV-TT efficacy	High resistance rates in Africa and some areas in Asia	Potential adverse events; costs	Currently, only NAC has been shown effective in clinical trials	Methodological aspects regarding low-quality studies; heterogeneity of strains
Emerging approaches	Vonoprazan-containing AST-guided therapies; non-invasive AST, including CLA resistance in stool samples		Sc-BQT; 10-day BQT (non-inferior efficacy and lower adverse events vs 14-day BQT); vonoprazan-containing BQT and TT; vonoprazan-amoxicillin; BQT with amoxicillin-tetracycline						NAC; rhamnolipids; SUNCs; Pistacia vera L. oleoresin; Casearia sylvestris leaf derivative; ARM1	Lactobacillus reuteri; Saccharomyces spp.
Future steps	Update regional and local resistance surveillance, especially in developing countries; validation of PCR-AST in diverse populations by correlating detected mutations with actual resistance profiles; identification of novel mutations and determinants of resistance through WGS; development and validation of non-invasive molecular-AST		Cost-effectiveness evaluation between empirical and AST-guided therapies in both RCTs and real-world data; evaluation of vonoprazan-containing therapies through multicenter RCTs in different regions and populations; evaluation of the impact of different antimicrobial therapies on the gut microbiota resistome through multicenter RCTs						Further evaluation of potential agents in high-quality clinical trials	Determination of specific strains and formulations through high-quality and multicenter RCTs

AMX: Amoxicillin; ARM1: Armeniaspirol A; AST: Antimicrobial susceptibility testing; BQT: Bismuth-containing quadruple therapy; CLA: Clarithromycin; DT: Dual therapy; LEV: Levofloxacin; MET: Metronidazole; NAC: N-acetylcysteine; Non-BQT: Non-bismuth-containing quadruple therapy; QT: Quadruple therapy; RCT: Randomized controlled trial; RIF: Rifabutin; Sc-BQT: Single-capsule bismuth-containing quadruple therapy; SUNCs: Silver Ultra-NanoClusters; TT: Triple therapy; WGS: Whole-genome sequencing.