The current status, mechanisms, and coping strategies of helicobacter pylori drug resistance

doi:10.19871/j.cnki.xfcrbzz.2025.03.013

Abstract

Abstract: Helicobacter pylori (H. pylori) infection is a global public health issue and is closely associated with a variety of gastric diseases, including chronic gastritis, peptic ulcers, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma. With the extensive use of antibiotics, drug resistance in H. pylori has gradually become a key factor in treatment failure. In recent years, the drug resistance rate of H. pylori has significantly increased worldwide, particularly to commonly used antibiotics such as clarithromycin, metronidazole, and levofloxacin. The mechanisms of resistance are complex and diverse, including alterations in antibiotic targets, upregulation of drug efflux pump systems, biofilm formation, and other mechanisms. To effectively address the issue of drug resistance, in addition to traditional antibiotic susceptibility testing-guided treatment, new therapeutic approaches should be explored, such as phage therapy, nanoparticle delivery of antibiotics, and vaccine development. Moreover, strategies like optimizing existing treatment regimens, extending treatment duration, and combining probiotics or traditional Chinese medicine with antibiotics have also shown certain therapeutic effects. This review article provides a comprehensive analysis of multiple relevant studies, focusing on the current status of drug resistance, mechanisms of resistance, and coping strategies. The aim is to offer reference for clinical treatment and further research.

Key words: Helicobacter pylori, Drug resistance, Resistance mechanism, Treatment

CLC Number:

R446.5

Fan Bing, Nie Yongbo, Pei Xiaogai, Li Zhipeng, Zhou Ming, Luo Yi, Xiang Qi. The current status, mechanisms, and coping strategies of helicobacter pylori drug resistance[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(3): 72-77.

References

[1] HOOI JK, LAI WY, NG WK.Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis[J]. Gastroenterology, 2017, 153(2):420-429.
[2] UEMURA N, OKAMOTO S, YAMAMOTO S, et al.Helicobacter pylori infection and the development of gastric cancer[J]. N Engl J Med, 2001, 345(11):784-789.
[3] TSHIBANGU-KABAMBA E, YAMAOKA Y.Helicobacter pylori infection and antibiotic resistance-from biology to clinical implications[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(9):613-629.
[4] HU Y, ZHANG Y, LIU Y, et al.Primary antibiotic resistance of Helicobacter pylori in China: a multicenter study[J]. Helicobacter, 2022, 27(5):e12849.
[5] WANG Y, ZHANG J, CHEN X, et al.Antibiotic resistance of Helicobacter pylori in different regions of China: a meta-analysis[J]. J Digest Dis, 2023, 24(5):243-252.
[6] 张淑贞,李雪宏,黄海燕,等. 深圳地区幽门螺杆菌临床分离株的耐药性分析[J/CD]. 新发传染病电子杂志,2021, 6(2):79-83.
[7] LOK SH, YAU TO, SUNG JJ.Molecular detection of Helicobacter pylori antibiotic resistance: current status and future directions[J]. Gut, 2020, 69(5):837-849.
[8] RIMBARA E, FISCHBACH LA, GRAHAM DY.Role of Helicobacter pylori outer membrane proteins and penicillin-binding proteins in amoxicillin resistance[J]. Antimicrob Agents Ch, 2008, 52(9):3296-3303.
[9] QURESHI SA, IQBAL Z, KHAN AA.Detection of Helicobacter pylori isolates with decreased susceptibility to amoxicillin in Karachi, Pakistan[J]. Braz J Infect Dis, 2011, 15(3):252-257.
[10] SARANATHAN S, DENG W, ZHENG Q.Helicobacter pylori antibiotic resistance: mechanisms and advances in diagnosis[J]. Clin Microbiol Rev, 2020, 33(3):e00002-e00018.
[11] ANIS ET, IQBAL J, ASIM B.Helicobacter pylori antibiotic resistance: an updated review[J]. Infect Drug Resist, 2021, 14:1403-1410.
[12] TANIH NF, MAHMUD R, PARASAKTHI N.Helicobacter pylori resistance to metronidazole: role of rdxA and frxA mutations[J]. Malays J Pathol, 2011, 33(1):31-36.
[13] TEH BT, MAHMUD R, PARASAKTHI N.Helicobacter pylori resistance to metronidazole: role of rdxA and frxA mutations[J]. Malays J Pathol, 2014, 36(1):19-24.
[14] MIFTAHUSSURUR M, YAMAOKA Y, AZUMA T.Mechanisms of Helicobacter pylori resistance to fluoroquinolones and rifamycins[J]. Helicobacter, 2016, 21(1):1-10.
[15] RIMBARA E, SASAKI T, MIFTAHUSSURUR M.Mutations in gyrA, gyrB, and grlA genes in Helicobacter pylori clinical isolates resistant to levofloxacin in Japan[J]. J Clin Microbiol, 2012, 50(4):1190-1194.
[16] HE Q, LI Y, ZHANG X.Application of artificial intelligence in Helicobacter pylori infection diagnosis and treatment[J]. J Gastroen Hepatol, 2022, 31(2):145-150.
[17] CAI Y, HU F, ZHANG H, et al.The role of efflux pumps in Helicobacter pylori antibiotic resistance[J]. Helicobacter, 2020, 25(1): e12680.
[18] KOUITCHEU MABEKU F, AKOACHERE JF, BOYOM FF.The role of efflux pumps in Helicobacter pylori resistance to antibiotics: a review[J]. Eur J Clin Microbiol, 2019, 38(1):1-11.
[19] ATTARAN N, ASLANI A, GHAFFARI SH.Biofilm formation by Helicobacter pylori[J]. Arch Iran Med, 2016, 19(9): 587-592.
[20] YONEZAWA H, OSAKI T, KURATA S, et al.Helicobacter pylori in the mucus layer and its association with gastric inflammation[J]. Helicobacter, 2015, 20(3):197-204.
[21] ATTARAN N, ASLANI A, GHAFFARI SH.Helicobacter pylori biofilm: a new challenge in the treatment of Helicobacter pylori infection[J]. Arch Iran Med, 2017, 20(9):560-567.
[22] FAUZIA RFITRIANI N, PRASETYOPUTRI ED.Biofilm-forming ability of Helicobacter pylori isolates and its correlation with antibiotic resistance[J]. Acta Med Indones, 2020, 52(2):111-117.
[23] TSENG HH, LIN JT, YANG HB, et al.β-Lactamase production in Helicobacter pylori isolates in Taiwan[J]. Helicobacter, 2009, 14(2):113-117.
[24] MATTEO A, GAROFALO C, NISTA EC.Heteroresistance to clarithromycin in Helicobacter pylori[J]. J Clin Gastroenterol, 2008, 42(10):1124-1127.
[25] SELGRAD M, MALFERTHEINER P, SCHMID RM.Heteroresistance in Helicobacter pylori: a challenge for antimicrobial susceptibility testing[J]. Helicobacter, 2014, 19(4):259-265.
[26] GINGOLD BELFER R, DVIR I, KOREN R.Antibiotic susceptibility testing in Helicobacter pylori infection: current status and future directions[J]. World J Gastroenterol, 2021, 27(15):1443-1458.
[27] MALFERTHEINER P, MEGRAUD F, O'MORAIN CA. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report[J]. Gut, 2017, 66(1):6-30.
[28] CARDOS P, AMARO R, FERREIRA C, et al.Antibiotic resistance in Helicobacter pylori: current status and new insights[J]. Antibiotics, 2021, 10(5):522.
[29] O'MORAIN CA,MCNAMARA D,O'CONNOR A. Treatment of Helicobacter pylori infection[J]. Helicobacter, 2018, 23(Suppl 1):e12472.
[30] GISBERT JP.Rifabutin-containing regimens for Helicobacter pylori eradication[J]. Expert Rev Gastroent, 2020, 14(4):309-317.
[31] SUGANO K, TACK J, KUIPERS EJ.New antibiotics for Helicobacter pylori eradication[J]. Gut, 2022, 71(5):885-894.
[32] SGOURAS DN, MARAGKOUDAKIS PA, PETRAKI K.Probiotics in the treatment of Helicobacter pylori infection[J]. Helicobacter, 2020, 25(1):e12685.
[33] ZHANG Y, LI Y, WANG Z, et al.Probiotics in Helicobacter pylori eradication: a meta-analysis[J]. Helicobacter, 2023, 28(1):e12904.
[34] LI Y, ZHANG Y, WANG X.Traditional Chinese medicine in the treatment of Helicobacter pylori infection: a review[J]. CJIM, 2023, 29(1):76-84.
[35] TANG X, LIU X, ZHANG Y.The role of traditional Chinese medicine in the treatment of Helicobacter pylori infection[J]. CJIM, 2023, 29(1):85-92.
[36] BAO Y, CHEN Z, WANG X, et al.Efficacy and safety of a traditional Chinese medicine formula combined with standard quadruple therapy in the treatment of Helicobacter pylori-associated gastritis: a randomized controlled trial[J]. J Ethnopharmacol, 2022, 291:115124.
[37] DENG H, LIU X, LI Y.Mechanisms of combined treatment of Helicobacter pylori infection with antibiotics and traditional Chinese medicine[J]. CJIM, 2024, 20(1):70-76.
[38] MORAES TM, DE SOUSA DP, DE OLIVEIRA RS.Antimicrobial activity of limonene against Helicobacter pylori[J]. Phytomedicine, 2009, 16(10):905-912.
[39] DE SOUZA AC, DE OLIVEIRA RS, DE SOUSA DP.Antimicrobial activity of limonene against Helicobacter pylori: a review[J]. J Appl Microbiol, 2019, 127(2):303-312.
[40] GRANDE R, COELHO MA, SAAVEDRA MJ.Thymol and carvacrol: from plant compounds to antibacterial and antifungal agents[J]. Molecules, 2021, 26(3):614-625.
[41] SISTO F, LAUDADIO V, TUNDIS R.Antibacterial activity of thymol and carvacrol: from the bench to the food industry[J]. Molecules, 2021, 26(3):614-632.
[42] SISTO F, LAUDADIO V, TUNDIS R.Thymol and carvacrol: a review of bioactive phytochemicals with multiple health-promoting properties[J]. Int J Mol Sci, 2020, 21(12):4488.
[43] DE S, MAJUMDAR A, PAL A.Curcumin inhibits Helicobacter pylori-induced gastric epithelial cell proliferation by modulating the Sonic hedgehog signaling pathway[J]. Helicobacter, 2009, 14(3):218-227.
[44] SHETTY S, UPADHYAY R, SHETTY A.Curcumin: a potential phytochemical against Helicobacter pylori infection[J]. Phytother Res, 2021, 35(2):665-676.
[45] KRZYZEK P, SALAJ R, KUSNIERCZYK P.Flavonoids as inhibitors of Helicobacter pylori virulence factors: a review[J]. Phytochem Rev, 2021, 20(4):1317-1334.
[46] YANG X, ZHANG Y, LIU Y, et al.The anti-Helicobacter pylori activity and mechanism of flavonoids[J]. Chin J Nat Medicines, 2022, 20(1):1-10.
[47] WU Y, LI Y, ZHANG Y, et al.The antibacterial activity of berberine against Helicobacter pylori and its mechanism[J]. Chin J Nat Medicines, 2023, 21(1):1-10.
[48] NAZARI P, DOWLATABADI-BAZAZ R, MOFID MR, et al.The antimicrobial effects and metabolomics footprinting of carboxyl-capped bismuth nanoparticles against Helicobacterpylori[J]. Crit Rev Microbiol, 2014, 172(2): 570-579.
[49] CUOMO P, PAPAIANNI M, FULGIONE A, et al.Aninnovative approach to control H.pylori-induced persistent inflammation and colonization[J]. Microorganisms, 2020, 8(8):1214.