A REVIEW ON PREVALENCE AND GENETIC ELEMENTS ASSOCIATED WITH ANTIBIOTIC RESISTANCE OF H. PYLORI: A NARRATIVE REVIEW
DOI:
https://doi.org/10.71000/en1w1g28Keywords:
Antimicrobial resistance, , Helicobacter pylori, Global trends, Genetic mutations, Multidrug resistance, Narrative review.Abstract
Background: The management of Helicobacter pylori infection has become increasingly complex due to the global rise in antibiotic resistance, which undermines the effectiveness of conventional eradication regimens. This resistance is largely driven by inappropriate antibiotic use and regional variations in prescribing practices. Understanding the mechanisms and trends of resistance is crucial to designing effective, locally adapted treatment strategies.
Objective: This review aimed to analyze global trends in H. pylori antibiotic resistance and identify genetic determinants associated with antimicrobial resistance to commonly used antibiotics, including amoxicillin, metronidazole, clarithromycin, levofloxacin, and tetracycline.
Main Discussion Points: Evidence from multiple countries indicates a significant rise in resistance to several antibiotics, with metronidazole resistance reaching up to 100% in India and clarithromycin and tetracycline resistance rates exceeding 90% in some regions. Levofloxacin resistance remained relatively lower but showed a progressive increase in East Asia. Multidrug resistance, particularly the combination of metronidazole and clarithromycin, was notably high in Korea (40.3%). Genetic studies revealed key mutations responsible for resistance: A2143G in the 23S rRNA gene for clarithromycin, amino acid substitutions in the PBP1A gene for amoxicillin, mutations in the 16S rRNA gene for tetracycline, gyrA/gyrB substitutions for levofloxacin, and nucleotide alterations in the rdxA gene for metronidazole.
Conclusion: There is marked geographic and temporal variation in H. pylori resistance patterns. Continuous antimicrobial surveillance and genotype-based diagnostic approaches are essential to guide region-specific therapy and curb resistance development.
References
Kim JJ, Kim JG, Kwon DH, El-Zaatari FA, Osato MS, Graham DY. Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J Antimicrob Chemother. 2001;47(4):459–61.
Koletzko S, Richy F, Bontems P, Celinska-Cedro D, Crone J, Kalach N, et al. Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe. Gut. 2006;55(12):1711–6.
Otth L, Wilson M, Fernández H, Otth C, Toledo C, Cárcamo C, et al. Isolation of Helicobacter pylori in gastric mucosa and susceptibility to five antimicrobial drugs in Southern Chile. Braz J Microbiol. 2011;42(1):442–7.
Ahmed KS, Khan AA, Ahmed I, Tiwari SK, Habeeb MA, Ahi JD, et al. Determination of antibiotic sensitivity pattern of Helicobacter pylori isolates from South India population by epsilometer Test (E-Test). Adv Microbiol. 2012;2:263–7.
Biernat MM, Poniewierska-Baran A, Bińkowska A, Głowacka A, Kempińska-Mirosławska B, Młynarczyk G, et al. Antimicrobial susceptibility of Helicobacter pylori isolates from Lower Silesia, Poland. Arch Med Sci. 2014;10(3):505–9.
Diab M, El-Shenawy A, El-Shenawy R, El-Morsy F. Detection of antimicrobial resistance genes of Helicobacter pylori strains to clarithromycin, metronidazole, amoxicillin and tetracycline among Egyptian patients. Egypt J Med Hum Genet. 2018;19(4):417–23.
Llanes R, Martínez MJ, Fernández L, Pérez L, Valdés L, Valdés AE, et al. Phenotypic and genetic characterization of antimicrobial profiles of Helicobacter pylori strains in Cuba. J Health Popul Nutr. 2010;28(2):124–30.
Azzaya D, Purevdorj E, Tserendorj T, Khasag O, Erdenebaatar J, Sarantuya J. High antibiotic resistance of Helicobacter pylori and its associated novel gene mutations among the Mongolian population. Microorganisms. 2020;8(7):1062.
Farzi N, Ghotaslou R, Nahaei MR, Akhi MT, Nikvash S, Asgharzadeh M, et al. High prevalence of antibiotic resistance in Iranian Helicobacter pylori isolates: importance of functional and mutational analysis of resistance genes and virulence genotyping. J Clin Med. 2019;8(11):2004.
Korona-Glowniak I, Siwiec R, Młynarczyk-Bonikowska B, Gościniak G. Antibiotic resistance and genotypes of Helicobacter pylori strains in patients with gastroduodenal disease in Southeast Poland. J Clin Med. 2019;8(7):1071.
Saniee P, Siavoshi F, Alikhani MY, Malekzadeh R. Helicobacter pylori multidrug resistance due to misuse of antibiotics in Iran. Arch Iran Med. 2018;21(7):283–8.
Siavoshi F, Saniee P, Malekzadeh R. Effective antimicrobial activity of rifabutin against multidrug-resistant Helicobacter pylori. Helicobacter. 2018;23(6):e12531.
Lee JH, Ahn YW, Lee DH, Kim N, Kang JM, Kim SE, et al. Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: a prospective multicenter study. Helicobacter. 2019;24(4):e12592.
An B, Moon BS, Kim H, Lim HC, Lee YC, Lee G, et al. Antibiotic resistance in Helicobacter pylori strains and its effect on eradication rates in a single center in Korea. Ann Lab Med. 2013;33(6):415–21.
Boyanova L, Stancheva I, Markovska R, Yordanov D, Gergova G, Mitov I. Helicobacter pylori susceptibility to fosfomycin, rifampin, and five usual antibiotics for H. pylori eradication. Diagn Microbiol Infect Dis. 2014;79(3):358–61.
Park JY, Shin TS, Kim JS, Kim JH, Kim BJ, Lee BH, et al. The prevalence of multidrug resistance of Helicobacter pylori and its impact on eradication in Korea from 2017 to 2019: a single-center study. Antibiotics (Basel). 2020;9(10):646.
Su P, Li Y, Li H, Zhang J, Lin L, Wang Q, et al. Antibiotic resistance of Helicobacter pylori isolated in the Southeast Coastal Region of China. Helicobacter. 2013;18(4):274–9.
Siddiqui TR, Ahmed W, Arif A, Qureshi H, Mehraj V, Awan S, et al. Emerging trends of antimicrobial resistance in Helicobacter pylori isolates obtained from Pakistani patients: the need for consideration of amoxicillin and clarithromycin. J Pak Med Assoc. 2016;66(6):710–6.
Vazirzadeh J, Shokri-Shirvani J, Salek R, Amraei M, Kafil HS. Molecular assessment of resistance to clarithromycin in Helicobacter pylori strains isolated from patients with dyspepsia by fluorescent in situ hybridization in the center of Iran. Biomed Res Int. 2020;2020:1–7.
Ribeiro ML, Vitiello L, Miranda MC, Benvengo YH, Godoy AP, Mendonça S, et al. Mutations in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori isolates in Brazil. Ann Clin Microbiol Antimicrob. 2003;2(1):1–4.
Yamade M, Furuta T, Yamamoto T, Uotani T, Higuchi K, Ando T, et al. Resistance of Helicobacter pylori to quinolones and clarithromycin assessed by genetic testing in Japan. J Gastroenterol Hepatol. 2011;26(9):1457–61.
Miftahussurur M, Nusi IA, Graham DY, Yamaoka Y. Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal. BMC Microbiol. 2016;16(1):1–10.
Zhang Y, Wu J, Zhang J, Zhao Q, Guo Z, Jin Z, et al. Mutations in the antibiotic target genes related to clarithromycin, metronidazole and levofloxacin resistance in Helicobacter pylori strains from children in China. Infect Drug Resist. 2020;13:311–21.
Phan TN, Santona A, Tran VH, Tran TP, Le VA, Le BT, et al. High rate of levofloxacin resistance in a background of clarithromycin- and metronidazole-resistant Helicobacter pylori in Vietnam. Int J Antimicrob Agents. 2015;45(3):244–8.
Miyachi H, Miki I, Aoyama N, Shirasaka D, Matsumoto Y, Toyoda M, et al. Primary levofloxacin resistance and gyrA/B mutations among Helicobacter pylori in Japan. Helicobacter. 2006;11(4):243–9.
Abdollahi H, Ranjbar R, Abedian Kenari S, et al. A study of rdxA gene deletion in metronidazole resistant and sensitive Helicobacter pylori isolates in Kerman, Iran. 2011.
Solcà NM, Bernasconi MV, Piffaretti JC. Mechanism of metronidazole resistance in Helicobacter pylori: comparison of the rdxA gene sequences in 30 strains. Antimicrob Agents Chemother. 2000;44(8):2207–10.
Cho H, Uehara T, Bernhardt TG. β-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell. 2014;159(6):1300–11.
Mlynarczyk G, Mlynarczyk A, Jeljaszewicz J. Epidemiological aspects of antibiotic resistance in respiratory pathogens. Int J Antimicrob Agents. 2001;18(6):497–502.
Kim BJ, Kim JG. Substitutions in penicillin-binding protein 1 in amoxicillin-resistant Helicobacter pylori strains isolated from Korean patients. Gut Liver. 2013;7(6):655–61.
Gerrits MM, Godoy AP, Kuipers EJ, van Vliet AH, Mendonça S, Stoof J, et al. Alterations in penicillin-binding protein 1A confer resistance to β-lactam antibiotics in Helicobacter pylori. Antimicrob Agents Chemother. 2002;46(7):2229–33.
Glocker E, Berning M, Gerrits MM, Kusters JG, Kist M. Real-time PCR screening for 16S rRNA mutations associated with resistance to tetracycline in Helicobacter pylori. Antimicrob Agents Chemother. 2005;49(8):3166–70.
Wu JY, Hsu PI, Chen YH, Tseng HH, Tsay FW, Lai KH, et al. Tetracycline-resistant clinical Helicobacter pylori isolates with and without mutations in 16S rRNA-encoding genes. Antimicrob Agents Chemother. 2005;49(2):578–83.
Toledo H, López-Solís R. Tetracycline resistance in Chilean clinical isolates of Helicobacter pylori. J Antimicrob Chemother. 2010;65(3):470–3.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Sharista, Maissor Ahmed Nafees, Saif-Ud-Din, Shan Alam, Imraan (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
