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22-09-2023 | Antibiotic | Narrative review

Current paradigms in the management of refractory Helicobacter pylori infection

Authors: Vaneet Jearth, Manas Kumar Panigrahi

Published in: Indian Journal of Gastroenterology

Abstract

Helicobacter pylori is the most prevalent chronic bacterial infection, with approximately half of the world’s population estimated to be colonized. The World Health Organization (WHO) has classified Helicobacter pylori as a class-I carcinogen. All main society guidelines recommend its eradication in infected individuals. The global trend indicates that eradication rates are decreasing annually and the likelihood of eradication decreases with each unsuccessful therapeutic attempt. Resistance to antibiotics in H. pylori strains is the leading cause for eradication failure. Still, drug resistance and treatment failure may be complex, multi-dimensional and associated with several other factors. Knowledge of these factors can aid in optimizing eradication rates. This review will focus on the factors associated with refractory H. pylori, with a particular emphasis on antibiotic resistance mechanisms and their clinical implications. Also, the most recent literature and recommendations available for determining an appropriate regimen after the failure of the first attempt at eradication will be discussed.

Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022; gutjnl-2022–327745. https://doi.org/10.1136/gutjnl-2022-327745.

Zamani M, Ebrahimtabar F, Zamani V, et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. 2018;47:868–76. https://doi.org/10.1111/apt.14561. CrossRefPubMed

Boyanova L, Hadzhiyski P, Gergova R, Markovska R. Evolution of Helicobacter pylori resistance to antibiotics: a topic of increasing concern. Antibiotics (Basel). 2023;12:332. https://doi.org/10.3390/antibiotics12020332. CrossRefPubMed

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660.

Plummer M, Franceschi S, Vignat J, Forman D, de Martel C. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 2015;136:487–90. https://doi.org/10.1002/ijc.28999. CrossRefPubMed

Ford AC, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut. 2020;69:2113–21. https://doi.org/10.1136/gutjnl-2020-320839. CrossRefPubMed

Lee YC, Chiang TH, Chou CK, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology. 2016;150:1113-24.e5. https://doi.org/10.1053/j.gastro.2016.01.028. CrossRefPubMed

Rokkas T, Rokka A, Portincasa P. A systematic review and meta-analysis of the role of Helicobacter pylori eradication in preventing gastric cancer. Ann Gastroenterol. 2017;30:414–23. https://doi.org/10.20524/aog.2017.0144.

Liou JM, Lee YC, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Treatment of refractory Helicobacter pylori infection-tailored or empirical therapy. Gut Liver. 2022;16:8–18. https://doi.org/10.5009/gnl20330.

10.

Misra V, Pandey R, Misra SP, Dwivedi M. Helicobacter pylori and gastric cancer: Indian enigma. World J Gastroenterol. 2014;20:1503–9. https://doi.org/10.3748/wjg.v20.i6.1503. CrossRefPubMedPubMedCentral

11.

Ramakrishna BS. Helicobacter pylori infection in India: the case against eradication. Indian J Gastroenterol. 2006;25:25–8. PubMed

12.

Ahuja V. The case for Helicobacter pylori eradication in India: sensationalism, skepticism and scientific salesmanship. Indian J Gastroenterol. 2006;25:20–4. PubMed

13.

Singh SP, Ahuja V, Ghoshal UC, et al. Management of Helicobacter pylori infection: the Bhubaneswar Consensus Report of the Indian Society of Gastroenterology. Indian J Gastroenterol. 2021;40:420–44. https://doi.org/10.1007/s12664-021-01186-4. CrossRefPubMed

14.

Shah SC, Iyer PG, Moss SF. AGA clinical practice update on the management of refractory Helicobacter pylori infection: expert review. Gastroenterology. 2021;160:1831–41. https://doi.org/10.1053/j.gastro.2020.11.059. CrossRefPubMed

15.

Cortés P, Nelson AD, Bi Y, et al. Treatment approach of refractory Helicobacter pylori infection: a comprehensive review. J Prim Care Community Health. 2021;12:21501327211014090. CrossRefPubMedPubMedCentral

16.

Sun K, Chen Y, Wang Z, et al. Application of a WeChat-based mini-app as a patient reminder in Helicobacter pylori eradication: a prospective multi-center randomized controlled study. BMC Gastroenterol. 2022;22:520. https://doi.org/10.1186/s12876-022-02614-1. CrossRefPubMedPubMedCentral

17.

Luo M, Hao Y, Tang M, et al. Application of a social media platform as a patient reminder in the treatment of Helicobacter pylori. Helicobacter. 2020;25:e12682. https://doi.org/10.1111/hel.12682. CrossRefPubMed

18.

Megraud F, Bruyndonckx R, Coenen S, et al. Helicobacter pylori resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community. Gut. 2021;70:1815–22. https://doi.org/10.1136/gutjnl-2021-324032. CrossRefPubMed

19.

Guo CG, Jiang F, Cheung KS, Li B, Ooi PH, Leung WK. Timing of prior exposure to antibiotics and failure of Helicobacter pylori eradication: a population-based study. J Antimicrob Chemother. 2022;77:517–23. https://doi.org/10.1093/jac/dkab415. CrossRefPubMed

20.

Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology. 2018;155:1372-82.e17. https://doi.org/10.1053/j.gastro.2018.07.007. CrossRefPubMed

21.

Kuo YT, Liou JM, El-Omar EM, et al. Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:707–15. https://doi.org/10.1016/S2468-1253(17)30219-4. CrossRefPubMed

22.

Graham DY, Canaan Y, Maher J, Wiener G, Hulten KG, Kalfus IN. Rifabutin-based triple therapy (RHB-105) for Helicobacter pylori eradication: a double-blind, randomized, controlled trial. Ann Intern Med. 2020;172:795–802. https://doi.org/10.7326/M19-3734. CrossRefPubMed

23.

Hallur V, Panigrahi M, Sable M, et al. Low clarithromycin resistance in virulent Helicobacter pylori from dyspeptic patients at a tertiary care centre in Odisha. Indian J Med Microbiol. 2022;40:211–6. https://doi.org/10.1016/j.ijmmb.2022.02.008. CrossRefPubMed

24.

Gehlot V, Mahant S, Mukhopadhyay AK, et al. Antimicrobial susceptibility profiles of Helicobacter pylori isolated from patients in North India. J Glob Antimicrob Resist. 2016;5:51–6. CrossRefPubMed

25.

Thyagarajan SP, Ray P, Das BK, et al. Geographical difference in antimicrobial resistance pattern of Helicobacter pylori clinical isolates from Indian patients: multicentric study. J Gastroenterol Hepatol. 2003;18:1373–8. CrossRefPubMed

26.

Shrestha AB, Pokharel P, Sapkota UH, et al. Drug resistance patterns of commonly used antibiotics for the treatment of Helicobacter pylori infection among South Asian countries: a systematic review and meta-analysis. Trop Med Infect Dis. 2023;8:172. https://doi.org/10.3390/tropicalmed8030172.

27.

Hulten KG, Lamberth LB, Kalfus IN, Graham DY. National and regional US antibiotic resistance to Helicobacter pylori: lessons from a clinical trial. Gastroenterology. 2021;161:342-4.e1. https://doi.org/10.1053/j.gastro.2021.03.045. CrossRefPubMed

28.

Kuo CJ, Lee CH, Chang ML, et al. Multidrug resistance: the clinical dilemma of refractory Helicobacter pylori infection. J Microbiol Immunol Infect. 2021;54:1184–7. https://doi.org/10.1016/j.jmii.2021.03.006. CrossRefPubMed

29.

Tshibangu-Kabamba E, Yamaoka Y. Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications. Nat Rev Gastroenterol Hepatol. 2021;18:613–29. https://doi.org/10.1038/s41575-021-00449-x. CrossRefPubMed

30.

Boyanova L, Hadzhiyski P, Kandilarov N, Markovska R, Mitov I. Multidrug resistance in Helicobacter pylori: current state and future directions. Expert Rev Clin Pharmacol. 2019;12:909–15. https://doi.org/10.1080/17512433.2019.1654858. CrossRefPubMed

31.

Phan TN, Santona A, Tran VH, et al. High rate of levofloxacin resistance in a background of clarithromycin-and metronidazole-resistant Helicobacter pylori in Vietnam. Int J Antimicrob Agents. 2015;45:244–8. CrossRefPubMed

32.

Mascellino MT, Porowska B, De Angelis M, Oliva A. Antibiotic susceptibility, heteroresistance, and updated treatment strategies in Helicobacter pylori infection. Drug Des Devel Ther. 2017;28:2209–20. https://doi.org/10.2147/DDDT.S136240. CrossRef

33.

Selgrad M, Tammer I, Langner C, et al. Different antibiotic susceptibility between antrum and corpus of the stomach, a possible reason for treatment failure of Helicobacter pylori infection. World J Gastroenterol. 2014;20:16245–51. https://doi.org/10.3748/wjg.v20.i43.16245. CrossRefPubMedPubMedCentral

34.

Keikha M, Karbalaei M. Prevalence of antibiotic heteroresistance associated with Helicobacter pylori infection: a systematic review and meta-analysis. Microb Pathog. 2022;170:105720. CrossRefPubMed

35.

Kocsmár É, Kocsmár I, Buzás GM, et al. Helicobacter pylori heteroresistance to clarithromycin in adults-new data by in situ detection and improved concept. Helicobacter. 2020;25:e12670. https://doi.org/10.1111/hel.12670. CrossRefPubMed

36.

Sugimoto M, Furuta T, Shirai N, et al. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Helicobacter. 2007;12:317–23. https://doi.org/10.1111/j.1523-5378.2007.00508.x. CrossRefPubMed

37.

Wang YC, Chen YP, Ho CY, et al. The impact of gastric juice pH on the intraluminal therapy for Helicobacter pylori infection. J Clin Med. 2020;9:1852. https://doi.org/10.3390/jcm9061852. CrossRefPubMedPubMedCentral

38.

Erah PO, Goddard AF, Barrett DA, Shaw PN, Spiller RC. The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection. J Antimicrob Chemother. 1997;39:5–12. https://doi.org/10.1093/jac/39.1.5. CrossRefPubMed

39.

Zhang Z, Liu ZQ, Zheng PY, Tang FA, Yang PC. Influence of efflux pump inhibitors on the multidrug resistance of Helicobacter pylori. World J Gastroenterol. 2010;16:1279–84. CrossRefPubMedPubMedCentral

40.

Kuo CH, Lu CY, Shih HY, et al. CYP2C19 polymorphism influences Helicobacter pylori eradication. World J Gastroenterol. 2014;20:16029–36. https://doi.org/10.3748/wjg.v20.i43.16029. CrossRefPubMedPubMedCentral

41.

Zihlif M, Bashaireh B, Rashid M, Almadani Z, Jarrar Y. Effect of major CYP2C19 genetic polymorphisms on Helicobacter pylori eradication based on different treatment regimens. Biomed Rep. 2022;16:2. CrossRefPubMed

42.

Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and proton pump inhibitor dosing. Clin Pharmacol Ther. 2021;109:1417–23. CrossRefPubMed

43.

El Rouby N, Lima JJ, Johnson JA. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018;14:447–60. CrossRefPubMedPubMedCentral

44.

Zhang HJ, Zhang XH, Liu J, et al. Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors. Pharmacol Res. 2020;152:104606. CrossRefPubMed

45.

Shah SC, Tepler A, Chung CP, et al. Host genetic determinants associated with Helicobacter pylori eradication treatment failure: a systematic review and meta-analysis. Gastroenterology. 2021;161:1443–59. CrossRefPubMed

46.

Fu J, Sun CF, He HY, et al. The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis. Pharmacogenomics. 2021;22:859–79. CrossRefPubMed

47.

Zhao X, Zhang Z, Lu F, et al. Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: an updated meta-analysis. Front Pharmacol. 2022;13:938419.

48.

Zullo A, Perna F, Hassan C, et al. Primary antibiotic resistance in Helicobacter pylori strains isolated in northern and central Italy. Aliment Pharmacol Ther. 2007;25:1429–34. CrossRefPubMed

49.

Ji Z, Han F, Meng F, Tu M, Yang N, Zhang J. The association of age and antibiotic resistance of Helicobacter pylori: a study in Jiaxing City, Zhejiang Province, China. Medicine (Baltimore). 2016;95:e2831. CrossRefPubMed

50.

Shiota S, Reddy R, Alsarraj A, El-Serag HB, Graham DY. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clin Gastroenterol Hepatol. 2015;13:1616–24. CrossRefPubMedPubMedCentral

51.

Suzuki T, Matsuo K, Ito H, et al. Smoking increases the treatment failure for Helicobacter pylori eradication. Am J Med. 2006;119:217–24. CrossRefPubMed

52.

Bai P, Zhou LY, Xiao XM, Luo Y, Ding Y. Susceptibility of Helicobacter pylori to antibiotics in Chinese patients. J Dig Dis. 2015;16:464–70. CrossRefPubMed

53.

White B, Winte M, DeSipio J, Phadtare S. Clinical factors implicated in antibiotic resistance in Helicobacter pylori patients. Microorganisms. 2022;10:322.

54.

Broutet N, Marais A, Lamouliatte H, et al. cagA Status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia. J Clin Microbiol. 2001;39:1319–22. CrossRefPubMedPubMedCentral

55.

Mégraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut. 2004;53:1374–84. https://doi.org/10.1136/gut.2003.022111.

56.

Ding SZ, Du YQ, Lu H, et al. Chinese consensus report on family-based Helicobacter pylori infection control and management (2021 Edition). Gut. 2022;71, 238–53.

57.

Smith SM, O’Morain C, McNamara D. Helicobacter pylori resistance to current therapies. Curr Opin Gastroenterol. 2019;35:6–13. CrossRefPubMed

58.

Brennan D, McNamara D, Smith SM. Noninvasive molecular tests for H. pylori. Cogoro: Hospital Healthcare Europe London; 2016. p. 197–9.

59.

Fernandez-Caso B, Miqueleiz A, Valdez VB, Alarcón T. Are molecular methods helpful for the diagnosis of Helicobacter pylori infection and for the prediction of its antimicrobial resistance? Front Microbiol. 2022;13:962063.

60.

Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6–30. https://doi.org/10.1136/gutjnl-2016-312288. CrossRefPubMed

61.

Gisbert JP. Empirical or susceptibility-guided treatment for Helicobacter pylori infection? A comprehensive review. Therap Adv Gastroenterol. 2020;13:1756284820968736.

62.

López-Góngora S, Puig I, Calvet X, et al. Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection. J Antimicrob Chemother. 2015;70:2447–55. CrossRefPubMed

63.

Chen H, Dang Y, Zhou X, et al. Tailored therapy versus empiric chosen treatment for Helicobacter pylori eradication: a meta-analysis. Medicine. 2016;95:e2750. CrossRefPubMedPubMedCentral

64.

Espada MNO, Gisbert JP. Non-bismuth quadruple concomitant treatment for H. pylori eradication: systematic review and meta-analysis. United Eur Gastroenterol J. 2021;9:325.

65.

Gingold-Belfer R, Niv Y, Schmilovitz-Weiss H, Levi Z, Boltin D. Susceptibility-guided versus empirical treatment for Helicobacter pylori infection: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2021;36:2649–58. https://doi.org/10.1111/jgh.15575. CrossRefPubMed

66.

Nyssen OP, Espada M, Gisbert JP. Empirical vs. Susceptibility-guided treatment of Helicobacter pylori infection: a systematic review and meta-analysis. Front Microbiol. 2022;13:913436.

67.

Nyssen OP, Vaira D, Pérez Aísa Á, et al. Empirical second-line therapy in 5000 patients of the European registry on Helicobacter pylori management (Hp-EuReg). Clin Gastroenterol Hepatol. 2022;20:2243–57.

68.

Liou J-M, Chen C-C, Chang C-Y, et al. Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial. J Antimicrob Chemother. 2013;68:450–6. CrossRefPubMed

69.

Puig I, López-Góngora S, Calvet X, et al. Systematic review: third-line susceptibility guided treatment for Helicobacter pylori infection. Therap Adv Gastroenterol. 2016;9:437–48. CrossRefPubMed

70.

Baylina M, Muñoz N, Sánchez-Delgado J, López-Góngora S, Calvet X, Puig I. Systematic review: would susceptibility-guided treatment achieve acceptable cure rates for second-line Helicobacter pylori therapy as currently practiced? Helicobacter. 2019;24:e12584. CrossRefPubMed

71.

Zhou L, Lu H, Song Z, et al. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin Med J (Engl). 2022;135:2899–910. https://doi.org/10.1097/CM9.0000000000002546.

72.

Boltin D, Levi Z, Gingold-Belfer R, et al. Effect of previous nitroimidazole treatment on Helicobacter pylori eradication success. J Clin Gastroenterol. 2020;54:333–7. CrossRefPubMed

73.

Graham DY, Lu H, Shiotani A. Vonoprazan-containing Helicobacter pylori triple therapies contribution to global antimicrobial resistance. J Gastroenterol Hepatol. 2021;36:1159–63. CrossRefPubMed

74.

Gisbert JP. Rifabutin for the treatment of Helicobacter pylori infection: a review. Pathogens. 2020;10:15.

75.

Gingold-Belfer R, Niv Y, Levi Z, Boltin D. Rifabutin triple therapy for first-line and rescue treatment of Helicobacter pylori infection: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2021;36:1392–402. CrossRefPubMed

76.

Ciccaglione AF, Tavani R, Grossi L, Cellini L, Manzoli L, Marzio L. Rifabutin containing triple therapy and rifabutin with bismuth containing quadruple therapy for third-line treatment of Helicobacter pylori infection: two pilot studies. Helicobacter. 2016;21:375–81. CrossRefPubMed

77.

Burgos-Santamaria D, McNicholl AG, Gisbert JP. Empirical Helicobacter pylori rescue therapy: an 18-year single-centre study of 1200 patients. GastroHep. 2019;1:311–24. CrossRef

78.

Caldas M, Pérez-Aisa Á, Tepes B, et al. The role of statins on Helicobacter pylori eradication: results from the European Registry on the management of H. pylori (Hp-EuReg). Antibiotics (Basel). 2021;10:965. https://doi.org/10.3390/antibiotics10080965.

79.

Hassan AM, Shawky MAE, Mohammed AQ, Haridy MA, Eid KA. Simvastatin improves the eradication rate of Helicobacter pylori: upper Egypt experience. Infect Drug Resist. 2019;12:1529–34.

80.

Rajabnia M, Sadeghi A, Abdi S, et al. Effect of statins on Helicobacter pylori eradication rate: a systematic review and meta-analysis. GE Port J Gastroenterol. 2021;29:322–30. CrossRefPubMedPubMedCentral

81.

Feng JR, Wang F, Qiu X, et al. Efficacy and safety of probiotic-supplemented triple therapy for eradication of Helicobacter pylori in children: a systematic review and network meta-analysis. Eur J Clin Pharmacol. 2017;73:1199–208. CrossRefPubMed

82.

Zhou B-G, Chen L-X, Li B, et al. Saccharomyces boulardii as an adjuvant therapy for Helicobacter pylori eradication: a systematic review and meta-analysis with trial sequential analysis. Helicobacter. 2019;24:e12651. CrossRefPubMed

83.

Zhang M, Zhang C, Zhao J, et al. Meta-analysis of the efficacy of probiotic supplemented therapy on the eradication of H. pylori and incidence of therapy associated side effects. Microb Pathog. 2020;147:104403. CrossRefPubMed

84.

Shi X, Zhang J, Mo L, Shi J, Qin M, Huang X. Efficacy and safety of probiotics in eradicating Helicobacter pylori: a network meta-analysis. Medicine (Baltimore). 2019;98:e15180. CrossRefPubMed

85.

Szajewska H. Pooling data on different probiotics is not appropriate to assess the efficacy of probiotics. Eur J Pediatr. 2014;173:975. CrossRefPubMedPubMedCentral

Title: Current paradigms in the management of refractory Helicobacter pylori infection
Authors: Vaneet Jearth
Manas Kumar Panigrahi
Publication date: 22-09-2023
Publisher: Springer India
Keywords: Antibiotic
Clarithromycin
Rifabutin
Amoxicillin
Helicobacter Pylori
Metronidazole
Levofloxacin
Gastric Cancer
Gastric Cancer
Tetracyclines
Published in: Indian Journal of Gastroenterology
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI: https://doi.org/10.1007/s12664-023-01448-3

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