Saudi Journal of Gastroenterology
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Table of Contents   
EDITORIAL  
Year : 2015  |  Volume : 21  |  Issue : 4  |  Page : 183-184
Selecting the optimum first-line treatment for H. pylori eradication


1 Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
2 Department of Medicine, Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia; Division of Gastroenterology, The McGill University Health Center, Montreal General Hospital, McGill University, Montreal, Canada

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Date of Web Publication29-Jul-2015
 

How to cite this article:
Ang TL, Almadi MA. Selecting the optimum first-line treatment for H. pylori eradication. Saudi J Gastroenterol 2015;21:183-4

How to cite this URL:
Ang TL, Almadi MA. Selecting the optimum first-line treatment for H. pylori eradication. Saudi J Gastroenterol [serial online] 2015 [cited 2021 Aug 2];21:183-4. Available from: https://www.saudijgastro.com/text.asp?2015/21/4/183/161638


Clarithromycin-based triple therapy had been the standard empiric treatment for Helicobacter pylori infection, while increasing rates of bacterial resistance to clarithromycin have decreased its efficacy in many countries.[1] Although sequential therapy was proposed as an alternative treatment strategy with initial studies demonstrating its superiority over triple therapy,[2] recent meta-analyses are inconclusive with regards to that notion depending on the duration of treatment.[3][4][5] It is important to have knowledge of local patterns of antibiotic resistance, as these differ across geographic regions[6] and what is considered an obsolete treatment in one area might be effective in another.[7] This randomized controlled study by Alsohaibani et al.[8] that compared triple therapy with sequential therapy in Saudi Arabia is important because it provided important local data in terms of treatment efficacy and antibiotic resistance patterns.

The study concluded that the efficacy of 10-day sequential therapy was similar to 14-day triple therapy, which is in keeping with the meta-analysis by Gatta et al.[3] However, the eradication rates were suboptimal with both regimens, being 62.3% and 67.6%, respectively. This was due to the high rates of antibiotic resistance. Amoxicillin resistance was 14.8%, clarithromycin resistance was 23.3%, and metronidazole resistance was 48.5%. It must be noted that sequential therapy is now also regarded by some experts to be less than ideal in the presence of clarithromycin resistance and to be more useful in regions with low resistance rates, similar to triple therapy,[2] and should not be used if one were to comply with the Maastricht IV/Florence consensus report.[9]

Tailored therapy with pre-treatment antibiotic susceptibility testing is ideal; however, access to these tests is limited and its use is impractical on a routine basis. In the search for optimum treatment, it is worthwhile to briefly review the determinants of treatment efficacy. For a treatment regimen to be optimum, it is crucial to use a combination of effective antibiotics, ensure compliance with adequate treatment duration, and achieve adequate acid suppression.

Historical data have demonstrated clearly that a combination of antibiotics is superior to a single antibiotic. In the early days of H. pylori eradication therapies, triple therapy comprising two antibiotics was shown to be clearly superior to dual therapy with a single antibiotic.[10] In addition, the presence of bacterial resistance resulted in the loss of treatment efficacy by reducing the number of effective antibiotics in the treatment regimen.[11]

Adequate treatment duration and compliance are important for treatment success. A recently published meta-analysis showed clearly that 14-day triple therapy was superior to 7- or 10-day therapy.[12] In addition, treatment compliance lower than 80% has been shown to decrease treatment success rates.[13]

Adequate acid suppression will prevent inactivation of antibiotics and facilitate the conversion of H. pylori from a dormant to replicative state where they become susceptible to antibiotics. In terms of acid suppression, proton pump inhibitors (PPI) are clearly superior to histamine-2 receptor antagonists. However, the metabolism and efficacy of PPI may be affected by cytochrome P450 genetic polymorphism with genotype CYP2C19 variation resulting in extensive, intermediate, and poor metabolizers. The homozygous extensive metabolizers have inadequate acid suppression when lansoprazole, omeprazole, and pantoprazole are used, resulting in reduced treatment efficacy. In contrast, because of differences in the metabolic pathway, the efficacy of esomeprazole and rabeprazole is not affected.[14] This may be of potential concern in Saudi Arabia, where a high prevalence rate of homozygous extensive metabolizer genotypes has been reported.[15] Vonoprazan is a newly developed potassium-competitive acid blocker that has been shown to be more potent than lansoprazole. In a preliminary study, triple therapy comprising vonoprazan, amoxicillin, and clarithromycin was compared with a regimen comprising lansoprazole, amoxicillin, and clarithromycin and was found to achieve significantly higher eradication rates (92.6% vs. 75.9%), even for subjects with clarithromycin resistance (82.0% vs. 40.0%).[16] More data are needed, but it is certainly a very promising acid suppressant.

Fourteen-day triple therapy and 10-day sequential therapy are not ideal empiric first-line treatments in Saudi Arabia. Thus, it is crucial to evaluate the efficacy and relevance of bismuth- and non-bismuth–based quadruple therapies such as concomitant and hybrid therapies. Bismuth-based quadruple therapy comprises bismuth, PPI, tetracycline, and metronidazole, and high eradication rates exceeding 90% can be achieved with this regimen even in the context of metronidazole resistance,[17] especially given the fact that the rate of tetracycline resistance in Saudi Arabia is low (2.3%).[8] Concomitant therapy consists of a PPI, amoxicillin, clarithromycin, and metronidazole given concurrently. Hybrid therapy combines sequential and concomitant therapy, with a 7-day first dual phase (PPI + amoxicillin) followed by a 7- day quadruple phase (PPI + amoxicillin + clarithromycin + metronidazole). These regimens have been shown to be effective even in the presence of high rates of clarithromycin and metronidazole resistance. A multicenter study reported that hybrid and concomitant therapies could achieve eradication rates of 90% and 91.7%, respectively.[13] In the context of Saudi Arabia, where the rates of resistance to clarithromycin, metronidazole, and amoxicillin are all high, non-bismuth –based quadruple therapies are probably less ideal than bismuth-based quadruple therapy and concomitant therapies would be expected to be more effective than hybrid therapies. Lastly, although quinolones have been incorporated into triple and quadruple therapy regimens successfully, it is uncertain whether such a strategy could achieve an acceptable eradication rate in Saudi Arabia, given the fact that levofloxacin resistance was reported to be 11.1%.[8]

To conclude, it is crucial to use an optimized treatment regimen. Based on available data, a 14-day bismuth-based quadruple therapy using esomeprazole or rabeprazole as the PPI may well be the preferred option for empiric first-line therapy in Saudi Arabia. Concomitant therapy could be another option, but conceptually it appears less ideal. A randomized controlled study comparing these two regimens in Saudi Arabia would be crucial and studies that confirm the true resistance rate to quinolones and the efficacy of quinolone-containing regimens are needed. Whichever strategy is taken, in the event of treatment failure, it would be worthwhile to perform antibiotic susceptibility testing to guide treatment in a given individual patient.



 
   References Top

1.
Camargo MC, García A, Riquelme A, Otero W, Camargo CA, Hernandez-García T, et al. The problem of Helicobacter pylori resistance to antibiotics: A systematic review in Latin America. Am J Gastroenterol 2014;109:485-95.  Back to cited text no. 1
    
2.
Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: Evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol 2014;12:177-86 e3; Discussion e12-3.  Back to cited text no. 2
    
3.
Gatta L, Vakil N, Vaira D, Scarpignato C. Global eradication rates for Helicobacter pylori infection: Systematic review and meta-analysis of sequential therapy. BMJ 2013;347:f4587.  Back to cited text no. 3
    
4.
Yoon H, Lee DH, Kim N, Park YS, Shin CM, Kang KK, et al. Meta-analysis: Is sequential therapy superior to standard triple therapy for Helicobacter pylori infection in Asian adults? J Gastroenterol Hepatol 2013;28:1801-9.  Back to cited text no. 4
    
5.
Kim JS, Ji JS, Choi H, Kim JH. Sequential therapy or triple therapy for Helicobacter pylori infection in Asians: Systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2014;38:118-25.  Back to cited text no. 5
    
6.
Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J Gastroenterol 2013;19:8168-80.  Back to cited text no. 6
    
7.
Ang TL, Fock KM, Song M, Ang D, Kwek AB, Ong J, et al. Ten-day triple therapy versus sequential therapy versus concomitant therapy as first-line treatment for Helicobacter pylori infection. J Gastroenterol Hepatol 2015;30:1134-9.  Back to cited text no. 7
    
8.
Alsohaibani F, Alashgar H, Alkahtani K, Kagevi I, Peedikayil M, Alfadda A, et al. Prospective trial in Saudi Arabia comparing the 14-day standard triple therapy with the 10-day sequential therapy for treatment of Helicobacter pylori infection. Saudi J Gastroenterol 2015;21:220-5.  Back to cited text no. 8
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9.
Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, et al.; European Helicobacter Study Group. Management of Helicobacter pylori infection--the Maastricht IV/Florence Consensus Report. Gut 2012;61:646-64.  Back to cited text no. 9
    
10.
Wong BC, Xiao SD, Hu FL, Qian SC, Huang NX, Li YY, et al. Comparison of lansoprazole-based triple and dual therapy of treatment of Helicobacter pylori-related duodenal ulcer: An Asian multicentre double-blind randomized placebo controlled study. Aliment Pharmacol Ther 2000;14:217-24.  Back to cited text no. 10
    
11.
Fischbach L, Evans EL. Meta-analysis: The effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther 2007;26:343-57.  Back to cited text no. 11
    
12.
Yuan Y, Ford AC, Khan KJ, Gisbert JP, Forman D, Leontiadis GI, et al. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev 2013;12:CD008337.  Back to cited text no. 12
    
13.
Molina-Infante J, Romano M, Fernandez-Bermejo M, Federico A, Gravina AG, Pozzati L, et al. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology 2013;145:121-8.e1.  Back to cited text no. 13
    
14.
Tang HL, Li Y, Hu YF, Xie HG, Zhai SD. Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: A meta-analysis of randomized clinical trials. PloS One 2013;8:e62162.  Back to cited text no. 14
    
15.
Saeed LH, Mayet AY. Genotype-phenotype analysis of CYP2C19 in healthy saudi individuals and its potential clinical implication in drug therapy. Int J Med Sci 2013;10:1497-502.  Back to cited text no. 15
    
16.
Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. A newly developed potassium-competitive acid blocker, vonoprazan vs. Lansoprazole in first-line triple therapy with amoxicillin, and clarithromycin for H pylori eradication-phase 3, double-blind study. Helicobacter 2014;19(Suppl 1):75-167.  Back to cited text no. 16
    
17.
Fischbach LA, van Zanten S, Dickason J. Meta-analysis: The efficacy, adverse events, and adherence related to first-line anti-Helicobacter pylori quadruple therapies. Aliment Pharmacol Ther 2004;20:1071-82.  Back to cited text no. 17
    

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Correspondence Address:
Tiing L Ang
Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.161638

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