N-acetyl cysteine as an adjunct to standard anti-Helicobacter pylori eradication regimen in patients with dyspepsia: A prospective randomized, open-label trial


1 Departments of Gastroenterology and Liver Disease, Kermanshah University of Medical Sciences, Iran

2 Kermanshah University of Medical Sciences, Iran

3 Poursina Hakim Research Institute Isfahan, Iran

4 Department of Community Medicine, Islamic Azad University, Najafabad Branch, Iran

5 Department of Internal Medicine, Isfahan University of Medical Sciences, Iran

6 Department of Gastroenterology and Liver Disease, Ahvaz University of Medical Sciences, Iran


Background: Increasing antibiotic resistance of Helicobacter pylori (H. pylori) which is associated with diseases of the upper gastrointestinal tract, has made alternative treatments necessary. This study compares the efficacy of adding N-acetyl cysteine (NAC) to standard regimen for H. pylori eradication.
Materials and Methods: We conducted a randomized, open-label trial, comparing the efficacy of 14 days of quadruple therapy with Amoxicillin, Bismuth citrate, Omeprazole, Clarithromycin (group A) versus 14 days of above regimen plus NAC (group B) in adult patients with dyspepsia. Primary objective was H. pylori eradication.Compliance and side effects were determined by questionnaires. Our analysis was by intention-to-treat (ITT) and per-protocol. This study is registered with www.IRCT.ir, number: IRCT201201078634N1.
Result: A total of 121 participants aged 21-76 years with a mean age of 44.5 ± 14.1, and 52.9% female, were randomly allocated a treatment: 60 with 14-day standard therapy and 61 with 14-day standard therapy with NAC. The eradication rate in groups A and B with ITT analyses was 49/60 (81.7%; 95% [confidence intervals] CI = 71.6-91.8%) and 50/61 (82%; 95% CI = 72-91.9%), respectively ( P = 0.96). In per-protocol analysis, the rate of H. pylori eradication in groups A and B was 45/54 (83.3%; 95% CI = 73.1-93.6%) and 45/53 (84.9%; 95% CI = 74.9-94.9%), respectively ( P = 0.82). Minor well tolerated side effects were reported in 15 (34.9%) and 21 (35.6%) patients of groups A and B, respectively, and only one therapy cessation in group A was created.
Conclusion: Standard 14-day triple-drug therapy with NAC is not preferable to standard drug regimens for H. pylori infection.


1. Alakkari A, Zullo A, O'Connor HJ. Helicobacter pylori and nonmalignant diseases. Helicobacter 2011;16:33-7.  Back to cited text no. 1
2. Zullo A, Hassan C, Cristofari F, Andriani A, De Francesco V, Ierardi E, et al. Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol 2010;8:105-10.  Back to cited text no. 2
3. Compare D, Rocco A, Nardone G. Risk factors in gastric cancer. Eur Rev Med Pharmacol Sci 2010;14:302-8.  Back to cited text no. 3
4. Kivi M, Johansson AL, Reilly M, Tindberg Y. Helicobacter pylori status in family members as risk factors for infection in children. Epidemiol Infect 2005;133:645-52.  Back to cited text no. 4
5. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: A combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001;49:347-53.  Back to cited text no. 5
6. Rowland M, Daly L, Vaughan M, Higgins A, Bourke B, Drumm B. Age-specific incidence of Helicobacter pylori. Gastroenterology 2006;130:65-72.  Back to cited text no. 6
7. Sonnenberg A, Lash RH, Genta RM. A national study of Helicobactor pylori infection in gastric biopsy specimens. Gastroenterology 2010;139:1894-1901.  Back to cited text no. 7
8. Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: The Maastricht III Consensus Report. Gut 2007;56:772-81.  Back to cited text no. 8
9. Massarrat S, Saberi-Firoozi M, Soleimani A, Himmelmann GW, Hitzges M, Keshavarz H. Peptic ulcer disease, irritable bowel syndrome and constipation in two populations in Iran. Eur J Gastroenterol Hepatol 1995;7:427-33.  Back to cited text no. 9
10. Malekzadeh R, Sotoudeh M, Derakhshan MH, Mikaeli J, Yazdanbod A, Merat S, et al. Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran. J Clin Pathol 2004;57:37-42.  Back to cited text no. 10
11. Gisbert JP, Calvet X, Gomollón F, Monés J. Eradication treatment of Helicobacter pylori. Recommendations of the II Spanish Consensus Conference. Med Clin (Barc) 2005;125:301-16.  Back to cited text no. 11
12. Malfertheiner P, Mégraud F, O'Morain C, Hungin AP, Jones R, Axon A, et al. Current concepts in the management of Helicobacter pylori infection: The Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther 2002;16:167-80.  Back to cited text no. 12
13. Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 2010;59:1143-53.  Back to cited text no. 13
14. Korownyk C, Kolber MR. Is quadruple therapy the new triple therapy for H pylori? Can Fam Physician 2012;58:58.  Back to cited text no. 14
15. Raymond J, Lamarque D, Kalach N, Chaussade S, Burucoa C. High level of antimicrobial resistance in French Helicobacter pylori isolates. Helicobacter 2010;15:21-7.  Back to cited text no. 15
16. Fiorini G, Zullo A, Gatta L, Castelli V, Ricci C, Cassol F, et al. Newer agents for Helicobacter pylori eradication. Clin Exp Gastroenterol 2012;5:109-12.  Back to cited text no. 16
17. O'Connor A, Gisbert J, O'Morain C. Treatment of Helicobacter pylori infection. Helicobacter 2009;14:46-51.  Back to cited text no. 17
18. Zagari RM, Bianchi-Porro G, Fiocca R, Gasbarrini G, Roda E, Bazzoli F. Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: The HYPER Study. Gut 2007;56:475-9.  Back to cited text no. 18
19. Paoluzi P, Iacopini F, Crispino P, Nardi F, Bella A, Rivera M, et al. 2-week triple therapy for Helicobacter pylori infection is better than 1-week in clinical practice: A large prospective single-center randomized study. Helicobacter 2006;11:562-8.  Back to cited text no. 19
20. Egan BJ, Marzio L, O'Connor H, O'Morain C. Treatment of Helicobacter pylori infection. Helicobacter 2008;13:35-40.  Back to cited text no. 20
21. Pajares G, Pajares-Villarroya R, Gisbert JP. H. pylori infection: Antibiotic resistance. Rev Esp Enferm Dig 2007;99:63-70.  Back to cited text no. 21
22. Moradimoghaddam F, saadatnia H, Arbabi H. Antibiotic resistance pattern of Helicobacter pylori in patients with chronic dyspepsia in Northeast of Iran. Med J Tabriz Univ Med Sci 2011;32:61-5.[Persian]  Back to cited text no. 22
23. Tran CD, Kritas S, Campbell MA, Huynh HQ, Lee SS, Butler RN. Novel combination therapy for the eradication of Helicobacter pylori infection in a mouse model. Scand J Gastroenterol 2010;45:1424-30.  Back to cited text no. 23
24. Huynh HQ, Couper RT, Tran CD, Moore L, Kelso R, Butler RN. N-acetylcysteine, a novel treatment for Helicobacter pylori infection. Dig Dis Sci 2004;49:1853-61.  Back to cited text no. 24
25. Ziment I. Acetylcysteine: A drug with an interesting past and a fascinating future. Respiration 1986;50:26-30.  Back to cited text no. 25
26. Matthews GM, Butler RN. Cellular mucosal defense during Helicobacter pylori infection: A review of the role of glutathione and the oxidative pentose pathway. Helicobacter 2005;10:298-306.  Back to cited text no. 26
27. Aslam S, Darouiche RO. Role of antibiofilm-antimicrobial agents in controlling device-related infections. Int J Artif Organs 2011;34:752-8.  Back to cited text no. 27
28. Zala G, Flury R, Wust J, Meyenberger C, Ammann R, Wirth HP. Omeprazole/amoxicillin: Improved eradication of Helicobacter pylori in smokers because of N-acetylcysteine. Schweiz Med Wochenschr 1994;124:1391-7.  Back to cited text no. 28
29. Gurbuz AK, Ozel AM, Ozturk R, Yildirim S, Yazgan Y, Demirturk L. Effect of N-acetyl cysteine on Helicobacter pylori. South Med J 2005;98:1095-7.  Back to cited text no. 29
30. Chey WD, Wong BC. Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007;102:1808-25.  Back to cited text no. 30
31. Laine L, Estrada R, Trujillo M, Fukanaga K, Neil G. Randomized comparison of differing periods of twice-a-day triple therapy for the eradication of Helicobacter pylori. Aliment Pharmacol Ther 1996;10:1029-33.  Back to cited text no. 31
32. Carron MA, Tran VR, Sugawa C, Coticchia JM. Identification of Helicobacter pylori biofilms in human gastric mucosa. J Gastrointest Surg 2006;10:712-7.  Back to cited text no. 32
33. Coticchia JM, Sugawa C, Tran VR, Gurrola J, Kowalski E, Carron MA. Presence and density of Helicobacter pylori biofilms in human gastric mucosa in patients with peptic ulcer disease. J Gastrointest Surg 2006;10:883-9.  Back to cited text no. 33
34. Yonezawa H, Osaki T, Kurata S, Zaman C, Hanawa T, Kamiya S. Assessment of in vitro biofilm formation by Helicobacter pylori. J Gastroenterol Hepatol 2010;25:S90-4.  Back to cited text no. 34
35. Cammarota G, Sanguinetti M, Gallo A, Posteraro B. Review article: Biofilm formation by Helicobacter pylori as a target for eradication of resistant infection. Aliment Pharmacol Ther 2012;36:222-30.  Back to cited text no. 35
36. Aslam S, Trautner BW, Ramanathan V, Darouiche RO. Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters. Antimicrob Agents Chemother 2007;51:1556-8.  Back to cited text no. 36
37. Perri F, Villani MR, Festa V, Quitadamo M, Andriulli A. Predictors of failure of Helicobacter pylori eradication with the standard 'Maastricht triple therapy'. Aliment Pharmacol Ther 2001;15:1023-9.  Back to cited text no. 37
38. Ziment I. Acetylcysteine: A drug that is much more than a mucokinetic. Biomed Pharmacother 1988;42:513-9.  Back to cited text no. 38
39. Parry MF, Neu HC. Effect of N-acetylcysteine on antibiotic activity and bacterial growth in vitro. J Clin Microbiol 1977;5:58-61.  Back to cited text no. 39
40. Millea PJ. N-acetylcysteine: Multiple clinical applications. Am Fam Physician 2009;80:265-9.  Back to cited text no. 40
41. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine: A safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 2007;7:355-9.  Back to cited text no. 41