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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 15  |  Issue : 4  |  Page : 225-228
Comparison of azithromycin and metronidazole in a quadruple-therapy regimen for Helicobacter pylori eradication in dyspepsia


1 Departments of Liver and Gastrointestinal Research, Infectious Disease Research, Iran University of Medical Sciences, Tehran, Iran
2 Tehran University of Medical Sciences, Tehran, Iran

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Date of Submission26-Aug-2008
Date of Acceptance08-Feb-2009
Date of Web Publication30-Sep-2009
 

   Abstract 

Background/Aim: Helicobacter pylori (H pylori) plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, and gastric neoplasms . Therefore, it is necessary to select an effective regimen for H pylori eradication . The aim of this study was to compare the efficacy of two quadruple-therapy regimens-one with azithromycin and the other with metronidazole-for H pylori eradication in patients with dyspepsia. Materials and Methods: In this double-blind randomized clinical trial conducted in Rasoule-Akram Hospital in 2006, we included 60 patients (aged 15-70 years) who had dyspepsia and H pylori infection as diagnosed by upper gastrointestinal endoscopy and rapid urease test. Patients were randomly assigned to receive a quadruple-therapy regimen for 2 weeks: 1) the MAO-B group (n = 30) received metronidazole 500 mg b.i.d, amoxicillin 1g b.i.d, omeprazole 20 mg b.i.d, and bismuth 240 mg b.i.d and 2) the AAO-B group (n = 30) received azithromycin 500 mg once daily for 1 week and amoxicillin 1g b.i.d, omeprazole 20 mg b.i.d, and bismuth 240 mg b.i.d for 2 weeks). H pylori eradication was assessed by the rapid urease test (RUT) 2 months after the cessation of treatment . Results: H pylori was eradicated in 68% and 69% of patients in the MAO-B and AAO-B groups, respectively. There was no significant difference in H pylori eradication rates between the two groups (P = 0.939). Conclusion: No significant difference exists between the two quadruple-therapy regimens that were tested.

Keywords: Azithromycin, Helicobacter pylori, metronidazole, quadruple-therapy regimens

How to cite this article:
Agah S, Shazad B, Abbaszadeh B. Comparison of azithromycin and metronidazole in a quadruple-therapy regimen for Helicobacter pylori eradication in dyspepsia. Saudi J Gastroenterol 2009;15:225-8

How to cite this URL:
Agah S, Shazad B, Abbaszadeh B. Comparison of azithromycin and metronidazole in a quadruple-therapy regimen for Helicobacter pylori eradication in dyspepsia. Saudi J Gastroenterol [serial online] 2009 [cited 2020 Nov 26];15:225-8. Available from: https://www.saudijgastro.com/text.asp?2009/15/4/225/56091


Gastritis caused by infection with Helicobacter pylori (H pylori) is one of the most common infectious diseases worldwide. H pylori plays an important role in the pathogenesis of chronic gastritis and peptic ulcer disease. [1],[2],[3],[4] There is strong evidence to show that H pylori infection may also be associated with gastric neoplasms, i.e., carcinoma of the stomach and primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). [5] The decrease in the incidence of H pylori infection in the developing countries has already led to a reduction in the incidence of gastric cancer. [6]

H pylori infection is one of the most common infections in Iran. In seroepidemiologic studies in different parts of this country its prevalence has been reported to be to 90% in adults older than 35 years. [7] A recent study in Ardabil in the north-western part of Iran, in which histopathology was used for screening, also revealed nearly 90% prevalence of H pylori infection in the normal population older than 40 years. [8]

Selection of a particular regimen for H pylori eradication will be influenced by several factors, including efficacy of the regimen, patient tolerance, the pattern of antibiotic resistance in the region, and the cost of the drugs. An acceptable regimen for H pylori eradication should show an eradication rate of 85-90% on intention-to-treat analysis. [9] Several drug regimens have been evaluated in Europe [10] and in the United States [11] for efficacy in H pylori eradication. Clinical experience in Iran and many other developing countries have demonstrated that the eradication rate of H pylori is much lower in these countries than in Western countries using the same treatment regimens; the short- and long-term recrudescence or reinfection rates are also much more than the rates reported from the West. [12]

Various regimens have been used for the eradication of this bacterium in Iran and they have shown different results. In this study, we compared the efficacy of two quadruple- therapy regimens for H pylori eradication in patients with dyspepsia: (A) omeprazole, amoxicillin, bismuth, and metronidazole and (B) omeprazole, amoxicillin, bismuth, and azithromycin. Regimen A is the conventional therapy in Iran.


   Materials and Methods Top


Study population

In this double-blind randomized clinical trial conducted in Rasoule-Akram Hospital in 2006, we included 60 patients (aged 15-70 years) with dyspepsia and H pylori infection; the cases were diagnosed by upper endoscopy and rapid urease test. Patients were not included if any one of the following conditions was present: History of antibiotic use during the 4 weeks preceding the study, gastric surgery, concurrent gastric carcinoma or other severe gastric disease, reflux esophagitis (of grade ≥2 according to Savary- Miller grading), sensitivity to any of the drugs to be used, pregnancy, or lactation. All patients had gastroenterological symptoms and were H pylori positive. Approval of the ethics committee of our institute was obtained before commencement of the study, as also written informed consent from all participants.

Treatment regimens

Patients who satisfied the inclusion criteria were randomly assigned to one of two groups. The MAO-B group (n = 30) received metronidazole 500 mg b.i.d, amoxicillin 1g b.i.d, omeprazole 20 mg b.i.d, and bismuth 240 mg b.i.d for 2 weeks and the AAO-B group (n = 30) received azithromycin 500 mg once daily (for 1 week) along with amoxicillin 1g b.i.d, omeprazole 20 mg b.i.d, and bismuth 240 mg b.i.d for 2 weeks. The efficacy of the treatment was assessed by achievement of H pylori eradication. The urease breath test (UBT) was performed 2 months after the cessation of treatment and a negative UBT was considered to indicate eradication of H pylori.

Statistical analysis

The sample size was calculated considering Chey et al. [13] study that found higher H pylori eradication rate with azithromycin 1g r/day for 3 days. The results were expressed as the mean ± standard deviation (SD) for quantitative variables andas percentages for categorical variables. Categorical variables were compared using the Chi square test; continuous variables were compared using the independent samples t- test for variables with normal distributions and the Mann- Whitney test for variables with non-normal distributions. P values of 0.05 or less were considered statistically significant. All statistical analyses were performed using SPSS version 13 and SAS version 9.1 for Windows.


   Results Top


Patients in the two groups were matched for demographic characteristics and endoscopic findings before treatment [Table 1] and [Table 2]. Out of 60 H pylori-positive patients who entered the study, six (i.e., five patients in the MAO-B group and one patient in the AAO-B group) discontinued treatment because of the side effects of the treatment). Thus, at the end of the study, 54 patients were available for inclusion in the analysis: 27 women and 27 men, with a mean age of 42.5±10.7 years (range: 15-70 years).

The endoscopic findings are shown in [Table 1]. There were no significant differences in the incidence of peptic ulcer, antral gastritis, and body gastritis between the two groups; however, severe reflux was found to be significantly more in the AAO-B group before treatment.

H pylori infection was eradicated in 68% of the 25 patients in the MAO-B group and in 69% of the 29 patients in the AAO-B group. There was no significant difference in the efficacy of the two regimens for eradication of H pylori (P = 0.939).


   Discussion Top


The prevalence of antibiotic resistance has increased substantially in recent years, and there has been a corresponding decrease in the eradication rates for H pylori infection. [14] Eradication rates in most Western countries have declined to unacceptable levels, with eradication therapy failing in approximately one in five patients. [15] A simple, short treatment regimen that would return eradication levels to that seen at the advent of H pylori treatment is urgently needed. [15] Causes of treatment failure include antibiotic resistance, poor compliance with treatment, short (7-10 days) duration of therapy, and drug-related side effects (such as skin flushing, headache, nausea, vomiting, sweating and a rapid heart rate, diarrhea, constipation, stomach cramps.). [16]

In our study, the H pylori eradication rate was similar in the two groups, being 68% and 69% in the MAO-B and AAO-B groups, respectively. According to published studies in Iran, about 37.5% of H pylori strains are resistant to metronidazole. [12] A quadruple-drug regimen, consisting of bismuth, a proton-pump inhibitor (PPI), amoxicillin, and metronidazole had good efficacy (92% eradication rate) in a study from Netherlands, [17] but this same regimen had less than 70% intention-to-treat eradication rate in Iranian

studies. [18] Also, quadruple therapy (omeprazole, bismuth, amoxicillin, and metronidazole) given for 1 week was also unsuccessful. [19] This quadruple-therapy regimen consisting of omeprazole, bismuth, amoxicillin, and metronidazole has a low eradication rate and is therefore not recommended in Iran.

Azithromycin has some special attributes that suggest that it would be a promising compound to be used in regimens for H pylori eradication. It is acid stable, has a long half-life, and achieves remarkably high concentrations in gastric tissue. [20],[21] There have been several clinical trials of azithromycin for the therapy of H pylori infection. [22],[23],[24]

Cammarota et al. found that the efficacy of clarithromycin was more than that of azithromycin; however, it had relatively more side effects than azithromycin. [25] In another study, with a regimen consisting of azithromycin, omeprazole, and metronidazole, the cure rate of H pylori was about 70%; however, the cure of H pylori infection improved gastritis. [26] Also in the Vladimir study, [27] the combination of a macrolide with amoxicillin was shown to provide higher eradication rates and therefore azithromycin at a dose of 1g per day for 3 days can be considered as a promising component of the triple PPI-based regimen. [27] In the Vladimir study, although azithromycin was administered only for 3 days, the dose was double that used by us and therefore its efficacy was similar to that in our study. Similar results were found in Chey et al. study. [13] In the study by Vcev et al., triple regimens consisting of pantoprazole, amoxicillin, and either azithromycin or clarithromycin gave poor eradication rates: 78% with the regimen containing clarithromycin and 71% with the regimen containing azithromycin. [28] According to their study, it was clear that due to the higher side effects of clarithromycin, the use of azithromycin was safer in H pylori eradication.


   Conclusion Top


No significant difference was detected between the two quadruple regimens that we tested for H pylori eradication. With the increase in the bacterial resistance to metronidazole, it seems that the use of azithromycin at a dose of 1g for 2 weeks in a quadruple regimen may be effective for achieving H pylori eradication.


   Acknowledgments Top


We would like to thank Farzan Institute for Research and Technology for technical assistance.

 
   References Top

1.Hunt RH, Mohamed AH. The current role of Helicobacter pylori eradication in clinical practice. Scand J Gastroenterol Suppl 1995;208:47-52.  Back to cited text no. 1      
2.Lind T, Veldhuyzen van Zanten S, Unge P, Spiller R, Bayerdφrffer E, O'Morain C, et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: The MACH I study. Helicobacter 1996;1:138-44.  Back to cited text no. 2      
3.Laine L, Frantz JE, Baker A, Neil GA. A United States multicentre trial of dual and proton pump inhibitor based triple therapies for Helicobacter pylori. Aliment Pharmacol Ther 1997;11:913-7.  Back to cited text no. 3      
4.Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group. Gut 1997;41:8-13.  Back to cited text no. 4      
5.IARC. Schistosomes, liver flukes and Helicobacter pylori. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Geneva: WHO Publications; 1994. p. 61.  Back to cited text no. 5      
6.Sipponen P, Kimura K. Intestinal metaplasia, atrophic gastritis and stomach cancer: Trends over time. Eur J Gastroenterol 1994;6:79-83.   Back to cited text no. 6      
7.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. 7      
8.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 North-West of Iran. J Clin Pathol 2004;57:37-42.  Back to cited text no. 8      
9.Marshall BJ, Armstrong JA, Francis GJ, Nokes NT, Wee SH. Antibacterial action of bismuth in relation to Campylobacter pyloridis colonization and gastritis. Digestion 1987;37:16-30.  Back to cited text no. 9      
10.Malfertheiner P, Mιgraud 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. 10      
11.NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA 1994;272:65-9.  Back to cited text no. 11      
12.Siavoshi F, Pourkhajeh AH, Merat S, Asl-Soleimani H, Heydarian E, Khatibian M, Malekzadeh R. Susceptibility of various strains of Helicobacter pylori to selected agents. Arch Iranian Med 2000;3:60-3.  Back to cited text no. 12      
13.Chey WD, Fisher L, Barnett J, Delvalle J, Elta GH, Hasler WL, et al. Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection. Aliment Pharmacol Ther 1998;12:1263-7  Back to cited text no. 13      
14.Mιgraud F. H pylori antibiotic resistance: Prevalence, importance, and advances in testing. Gut 2004;53:1374-84.   Back to cited text no. 14      
15.Vakil N. Helicobacter pylori treatment: A practical approach. Am J Gastroenterol 2006;101:497-9.  Back to cited text no. 15      
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17.de Boer WA, Driessen WM, Jansz AR, Tytgat GN. Quadruple therapy compared with dual therapy for eradication of Helicobacter pylori in ulcer patients: Results of a randomized prospective single-centre study. Eur J Gastroenterol Hepatol 1995;7:1189-94.  Back to cited text no. 17      
18.Mikaeli J, Mir-Nasseri MM, Manafi-Anari A. Evaluation of OAMB quadruple therapy for Helicobacter pylori eradication in patients with peptic ulcer disease and gastroduodenitis [in Persian] 2004;44:84-9.  Back to cited text no. 18      
19.Kaviani MJ, Malekzadeh R, Vahedi H, Sotoudeh M, Kamalian N, Amini M, et al. Various durations of a standard regimen (amoxicillin, metronidazole, colloidal bismuth subcitrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial. Eur J Gastroenterol Hepatol 2001;13:915-9.  Back to cited text no. 19      
20.Blandizzi C, Malizia T, Gherardi G, Costa F, Marchi S, Marveggio C, et al. Gastric mucosal distribution and clinical efficacy of azithromycin in patients with Helicobacter pylori related gastritis. J Antimicrob Chemother 1998;42:75-82.   Back to cited text no. 20      
21.Silva FM, Eisig JN, Chehter EZ, da Silva JJ, Laudanna AA. Low efficacy of an ultra-short term, once-daily dose triple therapy with omeprazole, azithromycin, and secnidazole for Helicobacter pylori eradication in peptic ulcer. Rev Hosp Clin Fac Med Sao Paulo 2002;57:9-14.  Back to cited text no. 21      
22.Ivashkin VT, Lapina TL, Bondarenko OY, Sklanskaya OA, Grigoriev PY, Vasiliev YV, et al. Azithromycin in a triple therapy for H.pylori eradication in active duodenal ulcer. World J Gastroenterol 2002;8:879- 82.  Back to cited text no. 22      
23.Krichhoff RM, Laufen H, Schδcke G, Kirchhoff G, Gallo E. Determination of azithromycin in gastric biopsy samples. Int J Clin Pharmacol Ther 1999;37:361-4.   Back to cited text no. 23      
24.Peitz U, Menegatti M, Vaira D, Malfertheiner P. The European meeting on Helicobacter pylori: Therapeutic news from Lisbon. Gut 1998;43:66- 9.   Back to cited text no. 24      
25.Cammarota G, Tursi A, Papa A, Montalto M, Veneto G, Cuoco L, et al. Helicobacter pylori eradication using one-week low-dose lansoprazole plus amoxicillin and either clarithromycin or azithromycin. Aliment Pharmacol Ther 1996;10:997-1000.   Back to cited text no. 25      
26.Di Mario F, Dal Bσ N, Grassi SA, Rugge M, Cassaro M, Donisi PM, et al. Azithromycin for the cure of Helicobacter pylori infection. Am J Gastroenterol 1996;91:264-7.  Back to cited text no. 26      
27.Ivashkin VT, Lapina TL, Bondarenko OY, Sklanskaya OA, Grigoriev PY, Vasiliev YV, et al. Azithromycin in a triple therapy for H.pylori eradication in active duodenal ulcer. World J Gastroenterol 2002;8:879- 82.   Back to cited text no. 27      
28.Vcev A, Stimac D, Ivandiζ A, Vceva A, Takac B, Pezeroviζ D. Pantoprazole, amoxicillin and either azithromycin or clarithromycin for eradication of Helicobacter pylori in duodenal ulcer. Alimen Pharmacol Ther 2000;14:69-72.   Back to cited text no. 28      

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Correspondence Address:
Babak Abbaszadeh
Flat 1, No 17, Siami Alley, Sattarkhan Ave., Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.56091

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