Treatment choices in young patients with Helicobacter pylori infection: Standard triple or bismuth-based quadruple therapies

Öz

Background and Aims:Helicobacter pylori is the most abundant pathogen in all age groups worldwide, and eradication rates of this pathogen are decreasing over time. We aimed to determine the efficacy rates of standard triple and bismuth-based quadruple therapies in young patients with dyspepsia, and in the event of eradication failure, to assess the success rates of rescue treatments with bismuthbased quadruple or levofloxacin-based triple protocols. Materials and Methods:A total of 116 Helicobacter pylori -positive young patients (≤35 years old) with dyspepsia were given either lansoprazole 30 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid for 14 days or bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid for 14 days. In case of eradication failure, levofloxacin, amoxicillin, and lansoprazole or bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid therapies were given as rescue treatments. Results:Helicobacter pylori eradication rates were 85.7% in the bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid group and 63.3% in the lansoprazole 30 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid group. Smoking, alcohol, and nonsteroidal antiinflammatory drug use had no effect on response; the only factor affecting the response rate was bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid treatment. The nonresponder patients in the lansoprazole 30 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid group and bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid groups were given bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid and levofloxacin, amoxicillin, and lansoprazole rescue treatments, respectively, and a 70% success rate was achieved in both groups. Conclusions:Even in young patients, who are supposed to be susceptible to clarithromycin-based treatment, the Helicobacter pylori eradication rates were lower with lansoprazole 30 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid treatment; thus, bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid protocol should be preferred as first-line treatment. There was no difference between the second-line treatment response rates of levofloxacin, amoxicillin, and lansoprazole and bismuth subsalicylate 300 mg qid, lansoprazole 30 mg bid, metronidazole 500 mg tid, and tetracycline 500 mg tid protocols

Anahtar Kelimeler

• Helicobacter pylori, dyspepsia, triple treatment, quadruple treatment, bismuth, clarithromycin, levofloxacin

Helicobacter pyloriinfeksiyonlu genç hastalarda tedavi seçenekleri; Standard üçlü veya bismuth bazlı dörtlü tedavi

Öz

Giriş ve Amaç: Helicobacter pylori dünyada tüm yaş gruplarında en sık görülen gastrik patojen olup bu patojenin eradikasyon oranları gün geçtikçe azalmaktadır. Bu çalışmanın amacı dispepsisi olan Helicobacter pylori pozitif genç hastalarda standard üçlü ve bizmut bazlı dörtlü tadavilerin başarı oranlarını belirlemek ve tedaviye cevapsızlık durumunda levofloksasin bazlı üçlü ve yine bizmut bazlı dörtlü ikinci basamak tedavilerinin başarı oranlarını saptamaktır. Gereç ve Yöntem: Otuz beş yaş altı 116 Helicobacter pylori pozitif dispepsili hasta çalışmaya alındı. Hastalar iki gruba ayrıldı bir gruba lansoprazol 30 mg bid, amoksisilin 1 gr bid, klaritromisin 500 mg bid 14 günlük tedavi diğer gruba bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid 14 günlük tedavi olarak verildi. Tedaviye yanıtsız olgulara, levofloksasin, amoksisilin, lansoprazol veya bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid tedavileri ikinci basamak tedavi olarak verildi. Bulgular: Helicobacter pylori eradikasyon oranları bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid grubunda %85.7 ve lansoprazol 30 mg bid, amoksisilin 1 gr bid, klaritromisin 500 mg bid grubunda %63.3 bulundu. İstatistiksel olarak sigara, alkol ve nonsteroid-antiinflamatuvar kullanımının tedavi cevabı üzerinde hiçbir etkisi bulunmaz iken tedaviyi etkileyen tek faktörün bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid tedavi seçeneği olduğu belirlendi. Tedaviye yanıtsızlarda ikinci basamak tedavi olarak lansoprazol 30 mg bid, amoksisilin 1 gr bid, klaritromisin 500 mg bid grubunda olanlara bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid ve bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid grubunda olanlara levofloksasin, amoksisilin, lansoprazol tedavisi verildi, her iki grupta da ikinci basamak tedavi ile %70 oranında başarı elde edildi. Sonuç: Klaritromisine duyarlı olmasını beklediğimiz genç hastalarda dahi Helicobacter pylori eradikasyon oranları lansoprazol 30 mg bid, amoksisilin 1 gr bid, klaritromisin 500 mg bid grubunda düşük olup bu hastalarda da bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid tedavisi ilk basamak tedavi olarak düşünülmelidir. İlk basamak tedaviye yanıtsız gençlerde ikinci basamak tedavi seçeneklerinden bizmut subsalisilat 300 mg qid, lansoprazol 30 mg bid, metronidazol 500 mg tid, tetrasiklin 500 mg tid ve levofloksasin, amoksisilin, lansoprazol arasında fark olmadığı saptanmıştır.

Anahtar Kelimeler

• Helicobacter pylori, dispepsi, üçlü tedavi, dörtlü tedavi, bizmut, klaritromisin, levofloksasin

Kaynakça

1. Ozaydin ANG, Cali S, Türkyilmaz AS. Turkey Helicobacter pylori prevalence survey 2003. [In Turkish]. İstanbul: Marmara Saglik ve Egitim Arastirma Vakfi, 2007; 42.
2. Malfertheiner P, Megraud F, O’Morain CA, et al. European Helico- bacter Study Group. Management of Helicobacter pylori infection - the Maastricht IV/Florence Consensus Report. Gut 2012; 61: 646- 64.
3. Howden CW, Hunt RH. Guidelines for the management of Heli- cobacter pylori infection. Ad Hoc Committee on practice para- meters of American College of Gastroenterology. Am J Gastroen- terol 1998; 93: 2330-8.
4. Nadir I, Yonem O, Ozin Y, et al. Comparison of two different treat- ment protocols in Helicobacter pylori eradication. South Med J 2011; 104: 102-5.
5. Ermis F, Akyüz F, Uyanikoglu A, et al. Second-line levofloxacin- based triple therapy’s efficiency for Helicobacter pylori eradication in patients with peptic ulcer. South Med J 2011; 104: 579-83.
6. Polat Z, Kadayifci A, Kantarcioglu M, et al. Comparison of levo- floxacin-containing sequential and standard triple therapies for the eradiation of Helicobacter pylori. Eur J Intern Med 2012; 23: 165-8.
7. Uygun A, Kadayifci A, Polat Z, et al. Comparison of bismuth–con- taining quadruple and concomitant therapies as a first–line treat- ment option for Helicobacter pylori. Turk J Gastroenterol 2012; 23: 8-13.
8. Ergül B, Dogan Z, Sarikaya M, et al. The efficacy of two-week quadruple first-line therapy with bismuth, lansoprazole, amoxicil- lin, clarithromycin on Helicobacter pylori eradication: a prospective study. Helicobacter 2013; 18: 454-8.

9. Gisbert JP, Pajares JM. 13 C-urea breath test in the diagnosis of Helicobacter pylori infection. Aliment Pharmacol Ther 2004; 20: 1001-17.
10. Malfertheiner P, Mégraud F, O’Morain C, et al. Current European concepts in the management of Helicobacter pylori infection the Maastricht Consensus Report. The European Helicobacter Pylori Study Group (EHPSG). Eur J Gastroenterol Hepatol 1997; 9: 1-2.
11. Lam SK, Talley NJ. Report of the 1997 Asia Pacific Consensus Con- ference on the management of Helicobacter pylori infection. J Gas- troenterol Hepatol 1998; 13: 1-12.
12. Kadayifci A, Buyukhatipoglu H, Savas CM, et al. Eradication of He- licobacter pylori with triple therapy: an epidemiologic analysis of trends in Turkey over 10 years. Clin Ther 2006; 28: 1960-6.
13. Philips RH, Whitehead MW, Lacey S, et al. Solubility, absorption, and anti-Helicobacter pylori activity of bismuth subnitrate and col- loidal bismuth subcitrate: in vitro data do not predict in vivo ef- ficacy. Helicobacter 2000; 5: 176-82.
14. Lu H, Zhang W, Graham DY. Bismuth-containing quadruple thera- py for Helicobacter pylori: lessons from China. Eur J Gastroenterol Hepatol 2013; 25: 1134-40.
15. Couturier MR, Marshall BJ, Goodman KJ, et al. Helicobacter pylori diagnostics and treatment: Could a lack of universal consensus be the best consensus? Clin Chem 2013; 60: 4 (Epub ahead of print).
16. Megraud F, Coenen S, Versporten A, et al.; Study Group partici- pants. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 2013; 62: 34-42.
17. Onder G, Aydın A, Akarca U, et al. High Helicobacter pylori resis- tance rate to clarithromycin in Turkey. J Clin Gastroenterol 2007; 41: 747-50.
18. Cagdas U, Otag F, Tezcan S, et al. Detection of Helicobacter pylori and antimicrobial resistance in gastric biopsy specimens. Microbiol Bul. 2012; 46: 398-409.
19. Bakir Ozbey S, Ozakin C, Keskin M. Antibiotic resistance rates of Helicobacter pylori isolates and the comparison of E-test and fluo- rescent in situ hybridization methods for the detection of clarithro- mycin resistant strains. Mikrobiol Bul 2009; 43: 227-34.
20. Fischbach LA, van Zanten S, Dickason J. Meta-analysis: the efficacy, adverse events, and adherence related to first line anti-Helicobacter pylori quadruple therapies. Alimentary Pharmacol Ther 2004; 20: 1071-82.
21. Salazar CO, Cardenas VM, Reddy RK, et al. Greater than 95% suc- cess with 14-day bismuth quadruple anti-Helicobacter pylori thera- py: a pilot study in US Hispanics. Helicobacter 2012; 17: 382-90.
22. Rimbara E, Fiscbach LA, Graham DY. Optimal therapy for Helico- bacter pylori infections. Nat Rev Gastroenterol Hepatol 2011; 8: 79-88.
23. Songür Y, Senol A, Balkarli A, et al. Triple or quadruple tetracycline based therapies versus standard triple treatment for Helicobacter pylori treatment. Am J Med Sci 2009; 338: 50-3.
24. Uygun A, Kadayifci A, Yesilova Z, et al. Comparison of sequential and standard triple drug regimen for Helicobacter pylori eradica- tion: a 14 day, open label, randomized, prospective, parallel-arm study in adult patients with non ulcer dyspepsia. Clin Ther 2008; 30: 528-34.
25. Jafri NS, Hornung CA, Howden CW. Meta-analysis: sequential ther- apy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med 2008; 148: 923-31.
26. Uygun A, Ozel AM, Sivri B, et al. Efficacy of a modified sequential therapy including bismuth subcitrate as first line therapy to eradi- cate Helicobacter pylori in Turkish population. Helicobacter 2012; 17: 486-90.
27. Kadayifci A, Uygun A, Kilciler G, et al. Low efficacy of clarithromy- cin including sequential regimens for Helicobacter pylori infection. Helicobacter 2012; 17: 121-6.
28. Molina-Infante J, Perez Gallardo B, Fernandez-Bermejo M, et al. Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication. Aliment Pharmacol Ther 2010; 31: 1077-84.
29. Zullo A, De Francesco V, Manes G, et al. Second-line and rescue therapies for Helicobacter pylori eradication in clinical practice. J Gastrointest Liver Dis 2010; 19: 131-4.
30. Wong WM, Gu Q, Chu KM, et al. Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as secondary line treatment of resistant Helicobacter pylori infection. Aliment Phar- macol Ther 2006; 23: 421-7.
31. Giannini EG, Bilardi C, Dulbecco P, et al. A study of 4- and 7-day triple therapy with rabeprazole, high dose levofloxacin and tinida- zole rescue treatment for Helicobacter pylori eradication. Aliment Pharmacol Ther 2006; 23: 281-7.
32. Gispert JP, Castro-Fernandez M, Bermejo F, et al.; H. pylori Study Group of the Asociacion Espanola de Gastroenterologia. Third line rescue therapy with levofloxacin after two H. pylori treatment fail- ures. Am J Gastroenterol 2006; 101: 243-7.
33. Calhan T, Kahraman R, Sahin A, et al. Efficacy of two levofloxacin- containing second-line therapies for Helicobacter pylori: a pilot study. Helicobacter 2013; 18: 378-83.
34. Namiot DB, Leszczynska K, Namiot Z, et al. Smoking and drinking habits are important predictors of Helicobacter pylori eradication. Adv Med Sci 2008; 53: 310-5.