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

Table 1 Summary of antibiotic resistance mechanisms and their global distribution

Resistance pattern	Main resistance mechanisms	Resistance prevalence by region (2013-2023)
		Africa	Americas	Asia	Europe	General
Clarithromycin	Nucleotide substitutions disrupting the antibiotic binding site in the 23S rRNA (A2142G, A2143G, A2142C, A2115G, G2212A, G2141A, A2144T, and T2289C mutations); efflux pump systems (HP0605-HP0607)	24.6% (16.4-33.9)1	16.0% (11.7-20.8)1	28.9% (26.6-31.2)1	21.3% (18.1-24.6)1	26.7% (24.7-28.8)1
Metronidazole	Partial inactivation of reductase enzymes required for metronidazole activity (mutations mainly in rdxA and possibly in frxA gene)	84.2% (78.9-88.9)1	48.1% (43.2-53.1)1	66.1% (62.1-69.9)1	29.9% (24.0-36.1)1	59.6% (55.2-63.9)1
Levofloxacin	Disrupted antibiotic binding site in the DNA gyrase (mainly gyrA but also gyrB gene mutations)	14.3% (0-49.9)1	25.0% (5.2-52.8)1	31.4% (28.3-34.6)1	13.3% (10.4-16.4)1	26.2% (23.5-28.9)1
Amoxicillin	Reduced affinity to PBPs (pbp1A gene mutations); porin protein alterations (hopB and hopC)	70.4% (64.0-76.4)1	4.8% (2.8-7.3)1	2.8% (2.0-3.7)1	0% (0-0.2)1	2.6% (1.8-3.5)1
Tetracycline	Disrupted antibiotic binding site in rRNA (mutations in 16S rRNA-encoding genes); efflux pump tetA[P] (HP1165), and other multidrug efflux systems	1% (0.1-2.5)1	1.1% (0-4.2)1	2.2% (1.3-3.2)1	0% (0-0)1	1.5% (0.9-2.3)1
Rifampicin	Amino acid exchanges disrupting antibiotic binding site in the β subunit of DNA-dependent RNA polymerase (mutations in rpoB gene)	0%3 (Algeria)[234,235]	0%-23.0%3 (Colombia)[236,237], 7.0%-19.0%3 (New York, United States)[238]	14.4%3 (Iran)[239], 5.4%-73.2%3 (China)[240]	11.4%3 (Belgium)[241], 8.3%3 (Bulgaria)[242], 1.2%3 (France)[243], 33.3%3 (Spain)[244]	Unavailable
Multi-drug resistance patterns	Accumulation of single-drug resistance genes; upregulation of multidrug efflux pump systems (hefA, gluP, HP1181 and HP1184); biofilm formation	1.6%3 (Egypt)[245], 15.7%3 (Cameroon)[246]	12.5%3 (Chile)[247]	10.0% (7-14)2 (children in East Asia)[248], 14.7%2 (India)[112], 24.9%3 (China)[249]	1.4%2 (Portugal)[116], 0.8%3 (Austria)[250], 2.4%3 (Spain)[251]	6.0%2 (children)[252]

¹Pooled primary resistance prevalence from 2013-2023 according to a meta-analysis by Yu et al[107].

²Prevalence of multiple antibiotic resistance according to meta-analyses conducted between 2013 and 2023.

³Rates derived from primary studies conducted between 2013 and 2023 (unavailable data from metanalyses). PBPs: Penicillin-binding proteins.