Adil ÇOŞKUN, Mustafa ÇELİK, Altay KANDEMİR

The Efficacy of Bismuth-based Quadruple and Sequential Therapies in Helicobacter pylori Eradication

Objective: New therapy regimens are needed for Helicobacter pylori (H. pylori) eradication because of increased resistance to the commonly used antibiotics. This study aimed to compare the efficacy of bismuth quadruple therapy versus sequential therapy for H. pylori eradication. Materials and Methods: Patients who presented with dyspepsia complaints and were diagnosed with H. pylori infection by histopathologic examination of biopsies obtained by gastroscopy were evaluated retrospectively. Two hundred and five patients who received bismuth-based quadruple therapy and sequential therapy for H. pylori eradication were included in the study. Bismuth-based quadruple therapy group were given pantoprazole 2x40 mg, bismuth subcitrate 4x300 mg, amoxicillin 2x1000 mg and metronidazole 3x500 mg for 14 days. In the bismuthbased sequential therapy group, the protocol was as follows; pantoprazole 2x40 mg (14 days), bismuth subcitrate 4x300 mg (14 days), amoxicillin 2x1000 mg (first 7 days), metronidazole 3x500 mg (second 7 days) and levofloxacin 1x500 mg (second 7 days). Eradication was determined by stool H. pylori Antigen test six weeks after the treatment. Results: A total of 102 patients in group 1 and 91 patients in group 2 completed the treatment and there was no significant difference between the two groups (p=0.310). H. pylori eradication rate showed no significant difference between the two groups (p=0.093), while group 1 attained a better eradication rate than group 2 on intention-to-treat, which was statistically significant (p=0.033). Conclusion: We achieved better eradication rates with bismuth-based quadruple therapy compared to the sequential therapy. We recommend bismuth-based quadruple regimen as the first-line eradication therapy to avoid drug incompatabilities seen during the sequential regime.

Helikobakter pilori Eradikasyonunda Bizmutlu Dörtlü Tedavi ile Bizmutlu Ardışık Tedavinin Etkinliği

Amaç: Helikobakter pilori (H. pilori) eradikasyon tedavisinde kullanılan antibiyotiklere karşı direncin artması nedeniyle yeni tedavi rejimlerine ihtiyaç duyulmaktadır. Bu çalışmada, H. pilori eradikasyonunda bizmutlu dörtlü tedavi ile bizmutlu ardışık tedavinin etkinliğini karşılaştırmayı amaçladık. Gereç ve Yöntemler: Dispepsi yakınması ile başvuran, yapılan gastroskopi ile alınan biyopsilerde histolojik inceleme sonrasında H. pilori saptanan hastalar retrospektif olarak değerlendirildi. Eradikasyon tedavisi olarak bizmutlu dörtlü tedavi ve bizmutlu ardışık tedavi alan 231 hasta çalışmaya alındı. Bizmutlu dörtlü tedavi alan gruba; 14 gün boyunca pantoprazol 2x40 mg, bizmut subsitrate 4x300 mg, amoksisilin 2x1000 mg, metronidazol 3x500 mg (14 gün) verilmişti. Bizmutlu ardışık tedavi alan gruba; pantoprazol 2x40 mg (14 gün), bizmut subsitrate 4x300 mg (14 gün), amoksisilin 2x1000 mg (ilk 7 gün), metronidazol 3x500 mg (ikinci 7 gün), levofloksasin 1x500 mg (ikinci 7 gün) verilmişti. Eradikasyon, tedaviden altı hafta sonra gaitada H. pilori Antijen testi ile ölçüldü. Bulgular: Grup 1’de 102 hasta, grup 2’de 91 hasta tedaviyi tamamlamış ve her iki grup arasında anlamlı bir fark bulunmamıştır (p=0,310). Her iki grup arasında protokol başına eradikasyon oranı açısından anlamlı bir fark bulunmamış (p=0,093), grup 1 rejimi intention-to-treat’de grup 2’ye göre daha iyi eradikasyon oranına ulaşmış ve istatistiksel olarak anlamlı bulunmuştur (p=0,033). Sonuç: Bizmut bazlı dörtlü tedavi ile ardışık tedaviye oranla daha iyi bir eradikasyon oranlarına ulaştık. Ardışık tedavi sırasında görülebilen ilaç uyumsuzluğu nedeniyle birinci basamak eradikasyon tedavisinde bizmut bazlı dörtlü tedavi rejiminin kullanılmasını önermekteyiz.

PDF

___

1. Morgan DR, Crowe SE. Helicobacter pylori infection. In: Sleisenger MH, Fordtran JS, (Eds). Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 10th ed. Philedelphia: Saunders, 2010; 856-67.

2. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol 2017; 112: 212-39.

3. Roubaud Baudron C, Franceschi F, Salles N, Gasbarrini A. Extragastric diseases and Helicobacter pylori. Helicobacter 2013; 18: 44-51.

4. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 2017; 153: 420-9.

5. Sezikli M, Çetinkaya ZA, Güzelbulut F, Yeşil A, Coşgun S, Kurdaş OÖ. Supplementing vitamins C and E to standard triple therapy for the eradication of Helicobacter pylori. J Clin Pharm Ther 2012; 37: 282-5.

6. Avşar E, Tiftikçi A, Poturoğlu S, Erzin Y, Kocakaya O, Dinçer D, et al. A multicenter, randomized, prospective study of 14-day ranitidine bismuth citrate vs. lansoprazole-based triple therapy fort he eradication of Helicobacter pylori in dyspeptic patients. Turk J Gastroenterol 2013; 24: 316-21.

7. Lee JY, Park KS. Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies. Gastroenterol Res Pract 2016; 2016: 9086581.

8. Malfertheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ, Axon AT, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 2017; 66: 6-30.

9. Polat Z, Kadayifci A, Kantarcioglu M, Ozcan A, Emer O, Uygun A. Comparison of levofloxacin-containing sequential and standard triple therapies for the eradication of Helicobacter pylori. Eur J Intern Med 2012; 23: 165-8.

10. Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 2006; 19: 449-90.

11. Kadayifci A, Buyukhatipoglu H, Cemil Savas M, Simsek I. Eradication of Helicobacter pylori with triple therapy: an epidemiologic analysis of trends in T urkey over 10 years. Clin Ther 2006; 28: 1960-6. 12. Onder G, Aydin A, Akarca U, Tekin F, Ozutemiz O, Ilter T. High Helicobacter pylori resistance rate to clarithromycin in Turkey. J Clin Gastroenterol 2007; 41: 747-50.

13. Sasaki M, Ogasawara N, Utsumi K, Kawamura N, Kamiya T, Kataoka H, et al. Changes in 12-year first-line eradication rate of Helicobacter pylori based on tripletherapy with proton pump inhibitor, amoxicillin and clarithromycin. J ClinBiochem Nutr 2010; 47: 53-8.

14. Cagdas U, Otag F, Tezcan S, Sezgin O, Aslan G, Emekdas G. [Detection of Helicobacter pylori and antimicrobial resistance in gastric biopsy specimens]. Mikrobiyol Bul 2012; 46: 398-409.

15. Kalem F, Ozdemir M, Basaranoglu M, Toy H, Baysal B. Helicobacter pylori isolates recovered from antral gastric biopsies of patients with dyspeptic symptoms: Antimicrobial resistance of metronidazole, clarithromycin and amoxicillin. Anatol J Clin Invest ig 2012; 6:37-40.

16. Caliskan R, Tokman HB, Erzin Y, Saribas S, Yuksel P, Bolek BK, et al. Antimicrobial resistance of Helicobacter pylori strains to five antibiotics, including levofloxacin, in Northwestern Turkey. Rev Soc Bras Med Trop 2015; 48: 278-84.

17. Ozbey SB, Cuneyt O, Murat K. Antbiotic resistance rates of Helicobacter pylori isolates and the comparison of E-Test and fluorescent in situ hybridization methods for the detection ofclarithromycin resistant strains. Mikrobiyol Bul 2009; 43: 227- 34.

18. Alkim H, Koksal AR, Boga S, Sen I, Alkim C. Role of Bismuth in the Eradication of Helicobacter pylori. Am J Ther 2017; 24: e751-7.

19. Dore MP, Graham DY, Mele R, Marras L, Nieddu S, Manca A, et al. Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection. Am J Gastroenterol 2002; 97: 857-60.

20. Gokcan H, Oztas E, Onal IK. Different bismuth-based therapies for eradicating Helicobacter pylori: Randomized clinical trial of efficacy and safety. Clin Res Hepatol Gastroenterol 2016; 40: 124-31.

21. Unler GK, Teke Ozgur G, Gokturk HS, Karakoca A, Erinanc OH. A Comparison of Five Different Treatment Regimens as the FirstLine Treatment of Helicobacter pylori in Turkey. Helicobacter 2016; 21: 279-85.

22. Kekilli M, Onal IK, Ocal S, Dogan Z, Tanoglu A. Inefficacy of triple therapy and comparison of two different bismuthcontaining quadrupleregimens as a firstline treatment option for helicobacter pylori. Saudi J Gastroenterol 2016; 22: 366-9.

23. Lee H, Hong SN, Min BH, Lee JH, Rhee PL, Lee YC, et al. Comparison of efficacy and safety of levofloxacin-containing versus standard sequential therapyin eradication of Helicobacter pylori infection in Korea. Dig Liver Dis 2015; 47: 114-8.

24. Romano M, Cuomo A, Gravina AG, Miranda A, Iovene MR, Tiso A, et al. Empirical levofloxacin-containing versus clarithromycincontaining sequential therapy for Helicobacter pylori eradication: a randomised trial. Gut 2010; 59: 1465-70.

25. Aydin A, Oruc N, Turan I, Ozutemiz O, Tuncyurek M, Musoglu A. The modified sequential treatment regimen containing levofloxacin for Helic