Sequential and concomitant non-bismuth quadruple therapies are ineffective for H. pylori eradication in Palestine. A randomized trial


Background: Increasing clarithromycin resistance has undermined the effectiveness of traditional clarithromycin-containing triple eradication therapy of Helicobacter pylori infections. Sequential and concomitant therapies show improved outcome with clarithromycin resistance. Aim: To evaluate the effectiveness of sequential and concomitant 4-drug non-bismuth therapies for eradication of Helicobacter pylori in a prospective, randomized, clinical trial conducted in Palestine. Patients and Methods: Patients who underwent upper endoscopy for a clinical indication and tested positive for rapid urease test were included. Subjects randomly allocated into two groups: One received a modified sequential therapy: esomeprazole 40 mg OD and amoxicillin 1 g BID for 5 days then esomeprazole 40 mg OD, clarithromycin 500 mg BID and tinidazole 500 mg BID for another 5 days. The other group received concomitant therapy in which the same 4 drugs and doses were all given daily for 10 days. Stool antigen was tested 4 weeks after completion of treatment. Results: Five hundred thirty three (533) patients were tested for H. pylori and 180 (34%) were positive; 141 patients were included in the study and 112 patients completed. The overall per protocol eradication rate was (74%; 95% CI = 65.9% - 82.1%). The eradication rates for sequential therapy was, (70.9%; 95% CI = 58.9% - 82.9%) and for concomitant therapy (77.2%; 95% CI = 66.3% - 88.1%). The results intention-to-treat were: sequential 61%, concomitant 57%. Conclusion: Neither sequential nor concomitant therapy achieved an acceptable H. pylori eradiation rate in Palestine.

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Abu-Safieh, Y. and Yamin, H. (2012) Sequential and concomitant non-bismuth quadruple therapies are ineffective for H. pylori eradication in Palestine. A randomized trial. Open Journal of Gastroenterology, 2, 177-180. doi: 10.4236/ojgas.2012.24034.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Suerbaum, S. and Michetti, P. (2002) Helicobacter pylori infection. The New England Journal of Medicine, 347, 1175-1186. doi:10.1056/NEJMra020542
[2] European Helicobacter Pylori Study Group (EHPSG) (2002) Current concepts in the management of Helico-bacter pylori infection—The Maastricht 2-2000 consensus report. Alimentary Pharmacology & Therapeutics, 16, 167-180. doi:10.1046/j.1365-2036.2002.01169.x
[3] Howden, C.W. and Hunt, R.H. (1998) Guidelines for the management of Helicobacter pylori infection. Ad Hoc committee on practice parameters of the American college of gastroenterology. American Journal of Gastroen-terology, 93, 2330-2338. doi:10.1111/j.1572-0241.1998.00684.x
[4] Megraud, F. (2004) H. pylori antibiotic resistance: Prevalence, importance, and advances in testing. Gut, 53, 1374-1384. doi:10.1136/gut.2003.022111
[5] Vakil, N. (2006) Helicobacter pylori treatment: A practical approach. American Journal of Gastroenterology, 101, 497-499. doi:10.1111/j.1572-0241.2006.00454.x
[6] Moayyedi, P. (2007) Sequential regimens for Helico-bacter pylori eradication. Lancet, 370, 1010-1012. doi:10.1016/S0140-6736(07)61455-X
[7] Zullo, A., De, F.V., Hassan, C., Morini, S. and Vaira, D. (2007) The sequential therapy regimen for Helicobacter pylori eradication: A pooled-data analysis. Gut, 56, 1353-1357. doi:10.1136/gut.2007.125658
[8] Jafri, N.S., Hornung, C.A. and Howden, C.W. (2008) Meta-analysis: Sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Annals of Internal Medicine, 148, 923-931.
[9] Graham, D.Y., Lu, H. and Yamaoka, Y. (2008) Therapy for Helicobacter pylori infection can be improved: Sequential therapy and beyond. Drugs, 68, 725-736. doi:10.2165/00003495-200868060-00001
[10] Treiber, G., Ammon, S., Schneider, E., et al. (1998) Amoxicillin/metronidazole/omeprazole/clarithromycin: A new, short quadruple therapy for Helicobacter pylori eradication. Helicobacter, 3, 54-58. doi:10.1046/j.1523-5378.1998.08019.x
[11] Okada, M., Oki, K., Shirotani, T., et al. (1998) A new quadruple therapy for the eradication of Helicobacter pylori. Effect of pretreatment with omeprazole on the cure rate. Journal of Gastroenterology, 33, 640-645. doi:10.1007/s005350050150
[12] Wu, D.C., Hsu, P.I., Wu, J.Y., et al. (2010) Sequential and concomitant therapy with four drugs is equally effective for eradication of H. pylori infection. Clinical Gas-troenterology and Hepatology, 8, 36-41. doi:10.1016/j.cgh.2009.09.030
[13] Yanai, A., Sakamoto, K., Akanuma, M., et al. (2012) Non Bismuth quadruple therapy for first line Helicobacter py-lori eradication: A randomized study in Japan. World Journal of Gastrointestinal Pharmacology and Therapeutics, 3, 1-6.
[14] Graham, D.Y. and Fischbach, L. (2010) Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut, 59, 1143-1153. doi:10.1136/gut.2009.192757
[15] Okada, M., Nishimura, H., Kawashima, M., et al. (1999) A new quadruple therapy for Helicobacter pylori: Influence of resistant strains on treatment outcome. Alimentary Pharmacology & Therapeutics, 13, 769-774. doi:10.1046/j.1365-2036.1999.00551.x
[16] Essa, A.S., Kramer, J.R., Graham, D.Y. and Treiber, G. (2009) Meta-analysis: Four-drug, three-antibiotic, non-bismuth-containing “concomitant therapy” versus triple therapy for Helicobacter pylori eradication. Helicobacter, 14, 109-118. doi:10.1111/j.1523-5378.2009.00671.x
[17] Sanchez-Delgade, J., Calvet, X., et al. (2008) Ten-day sequential treatment for Helicobacter pylori eradication in clinical practice. American Journal of Gastroenterology, 103, 2220-2223. doi:10.1111/j.1572-0241.2008.01924.x
[18] Gao, X.-Z., et al. (2010) Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter py-lori eradication. World Journal of Gastroenterology, 16, 4357-4362. doi:10.3748/wjg.v16.i34.4357
[19] Gisbert, J.P. and Calvet, X. (2012) Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori. Clinical and Experimental Gastro-enterology, 5, 23-34. doi:10.2147/CEG.S25419
[20] Robert, W., Frenck, Jr and Clemens, J. (2003) Helico-bacter in the developing world. Microbes and Infection, 5, 705-713. doi:10.1016/S1286-4579(03)00112-6
[21] Tomatari, F., Mobarez, A., Amini, A., et al. (2010) Helicobacter pylori resistance to metronidazole and clarithromycin in dyspepsic patients in Iran. Iranian Red Crescent Medical Journal, 12, 409-412.
[22] Greenberg, E.R., Anderson, G.L., Morgan, D.R., et al. (2011) 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: A randomised trial. Lancet, 378, 507-514. doi:10.1016/S0140-6736(11)60825-8
[23] Toros, A.B., Ince, A.T., Kesici, B., et al. (2011) A new modified concomitant therapy for Helicobacter pylori eradication in Turkey. Helicobacter, 16, 225-228. doi:10.1111/j.1523-5378.2011.00823.x
[24] Choi, C., Lee, D., Chon, I., et al. (2011) Concomitant therapy was more effective than ppi-base triple therapy in Korea: A preliminary report. Helicobacter, 16, 136.

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