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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2014  |  Volume : 25  |  Issue : 1  |  Page : 53-57
Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients


1 Clinical Research Development Center, Qom University of Medical Sciences, Qom, Iran
2 Deparment of Nephrology, Zanjan University of Medical Sciences, Zanjan, Iran
3 Deparment of Gastroetrology, Zanjan University of Medical Sciences, Zanjan, Iran

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Date of Web Publication7-Jan-2014
 

   Abstract 

To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.

How to cite this article:
Vafaeimanesh J, Jalalzadeh M, Nazarian M. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients. Saudi J Kidney Dis Transpl 2014;25:53-7

How to cite this URL:
Vafaeimanesh J, Jalalzadeh M, Nazarian M. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2019 Nov 14];25:53-7. Available from: http://www.sjkdt.org/text.asp?2014/25/1/53/124486

   Introduction Top


Helicobacter pylori is a gram negative bacil­lus with spiral shape and flagella that make it motile in the mucus environment. It is non-invasive and lives in the gastric mucus, with a small amount of the bacteria adhering to the mucosa. This organism has several acid-resis­tance mechanisms; most notably a highly expressed urease that catalyzes urea hydrolysis to produce buffering ammonia. [1],[2] The preva­lence of H. pylori is between 30% and 80% in various countries. In developing countries, more than 80% of adults have the bacillus; H. pylori is usually acquired in childhood. Spon­taneous acquisition or loss of H. pylori in adulthood is uncommon. Transmission occurs by the fecal-oral or the oral-oral route. H. pylori is easily cultured from vomitus and gastro esophageal refluxate, and is less easily cultured from stool. [3]

H. pylori infection has a role in the deve­lopment of gastrointestinal (GI) symptoms in hemodialysis (HD). [1],[2],[3],[4],[5],[6],[7] H. pylori is considered as a cause of gastritis and gastric ulcer. It has also been linked to gastric adenocarcinoma and gastric lymphoma. In addition, H. pylori has a role in the development of inflammation. [8] Inflammation in HD patients has been considered as one of the reasons of cardio­vascular events. [9] On the other hand, mortality in HD patients due to cardiovascular disease is ten to 30 times higher than that in the general population. [10] Thus, an appropriate therapeutic regimen is very important for the eradication of H. pylori infection among HD patients.

Extensive studies exist in the area of treat­ment regimens for H. pylori infection. It is now believed that triple or quadruple medi­cation therapy is needed for 10-14 days to meet the standard of care for an 85% eradica­tion rate of this infection. [4] A common regimen included clarithromycin, amoxicillin and either omeprazole or lansoprazole. [11],[12],[13] Azithromycin is an azalide similar to clarithromycin, but it has the benefit of once-a-day dosage. Most of the clinical trials have examined azithromycin in the treatment of H. pylori with a short dura­tion of treatment (2-7 days of therapy). This may explain the variable eradication rates, which ranged from 44-93%. [14],[15],[16],[17],[18],[19],[20]

We aim in this study to determine the effi­cacy of these agents in a randomized and blinded comparison of azithromycin with a clarithromycin regimen for the eradication of H. pylori in HD patients in 14-day therapy.


   Materials and Methods Top


This study was conducted from March to October 2008. Thirty-nine dialysis patients were enrolled in the study with an age range of 17-88 years. They were dialyzed in two HD centers (Valiasr and Beheshti hospitals) in Zanjan, Iran. Thirty-seven patients completed the treatment schedule (20 men and 19 women, with a mean age of 59 years). Two patients died due to myocardial infraction and were out of the study before the start of treatment. The mean duration of dialysis was 54.3 ± 16.7 months. The patients signed informed consents before their initial evaluation for upper GI tract symptoms.

Patients who had dyspepsia and were diag­nosed with H. pylori on initial testing were included in this study. To confirm the H. pylori infection, three types of tests were used: Anti-H. pylori serology, H. pylori stool Ag (HpSA) and urease breath test (UBT). If two of the three tests were positive, the patients were considered infected.

The exclusion criteria included a history of previous treatment for H. pylori, use of any of the proposed antibiotics in the previous six months and any known allergy to those medi­cations, as well as non-cooperation for per­forming the UBT. Then, with the help of a software for permutation randomization, the patients were randomly assigned to one of two treatments groups. One group received a regimen of omeprazole 20 mg, amoxicillin 500 mg and clarithromycin 500 mg (OAC), pres­cribed twice a day for 14 days. The second group received a regimen of omeprazole 20 mg, amoxicillin 500 mg and azithromycin 250 mg (OAAZ) prescribed twice a day for 14 days. Afterwards, we continued omeprazol in both groups for two more weeks. The subjects were not informed of which treatment they were receiving, but specific pill blinding did not take place. The subjects were followed for a total of ten weeks, which included the treat­ment period.

Any side-effects and change in symptoms were recorded. Exit interviews and pill count were conducted to evaluate compliance and determine side-effects. After the ten-week study period, the patients were re-evaluated for H. pylori infection by using the UBT. Eradi­cation was confirmed by negative results of UBT.


   Statistical Analysis Top


The chi-squared test with Pearson's correction, relative risk with 95% confidence interval, Student's test and paired-t-test were used, as appropriate, to test the statistical significance of the study results. All the statistical tests were two-sided. P-values of less than 0.05 were considered to be significant.


   Results Top


Eleven (55%) patients in the OAAz group and eight (42%) patients in OAC group were females, while nine (45%) patients in the OAAz group and 11 (57%) patients in the OAC group were males. The mean age of the patients in the two groups was 59 years. Eleven (55%) patients in the OAAz group and 14 (73.7%) patients in the OAC group had a history of dyspepsia. Demographic features of the patients in both groups are shown in [Table 1]. Accordingly, no significant statistical diffe­rence was observed between both groups in terms of gender, age, duration of dialysis, H. pylori infection and past history of dyspepsia.
Table 1: Demographic features of the patients in the two study groups

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After eight weeks of treatment, H. pylori era­dication was confirmed in 16 (80%) patients in the OAAz group and in 14 patients (82.4%) in the OAC group. No statistically significant difference in eradication rates was observed bet­ween the two study groups [Table 2].
Table 2: H. pylori eradication efficacy of triple therapy in the two study groups patients

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   Discussion Top


Peptic ulcer disease (PUD) occurs in up to one-fourth of patients with chronic renal failure (CRF). Some of the factors implicated in causing the appearance of peptic ulcer disease include hypergastrinemia, secondary hyperparathyroidism, drugs and, recently, H. pylori infection. [21],[22],[23],[24],[25] Treatment has required multiple drug regimens to assure eradication. Antibiotics used for this purpose in different regimens are azithromycin, clarithromycin, amoxicillin and metronidazole. Recently, clarithromycin resistance of 10% has been repor­ted in the US, with higher rates in other countries. [11],[12],[13] Therefore, newer regimens are being sought. Azithromycin is a medication similar to clarithromycin that has had a favorable pre­test probability of success. Azithromycin has two other potential advantages: (1) it has a once daily dosage and (2) it is available in a 5-day dose pack that may increase compliance. Previous studies using azithromycin-based re­gimens have had a wide range of results. There have been four trials that evaluated longer dur­ation azithromycin-based regimens. Al-Assi et al evaluated azithromycin, tetracycline and bismuth, and found a 50% eradication rate. [26]

Another study by Vcev et al found an eradi­cation rate of 85% with omeprazole, azithromycin and amoxicillin. [20] A third study, also by Vcev et al, evaluated pantoprazole, amoxicillin and either azithromycin or clarithromycin. The eradication rates in this study were found to be 71% and 81%, respectively. [20] A fourth study by Laurent et al using azithromycin, amoxicillin and ameprazole had an eradication rate of 38%. [27] In 1999, it was shown that lansoprazole and azithromycin have additive and synergistic activity in vitro against H. pylori.[28]

In our study, we used a triple-therapy regi­men based on change of antibiotics azithromycin and clarithromycin for the eradication of H. pylori in HD patients. We achieved a high rate of HP eradication (81%) after triple-drug therapy, but longer follow-up is needed to assess the long-term response.

In our study, we did not find a statistical dif­ference between the two regimens. The rate of eradication with the clarithromycin regimen was 82% when evaluated by negative results of UBT. The azithromycin-based regimen achieved an eradication rate of 80% by negative results of UBT. In vitro, azithromycin is bactericidal to H. pylori. In 1998, a study revealed that the gastric mucosa concentrations of azithromycin were significantly higher than the plasma con­centrations. This supported our hypothesis that it would be an effective antibiotic for the treatment of H. pylori. [29] However, in 1999, it was shown that although mucosal concen­trations reached levels much greater than the in vitro minimum inhibitory concentration, the gastric fluid levels of azithromycin were undetectable. [30] Although the antibiotic is delivered to the appropriate target organ, it does not seem to reach the desired concentration in the gastric fluid and mucous layer where the organism lives. This most likely explains the inability of azithromycin to achieve appro­priate eradication rates. Based on our data and new information about azithromycin concen­trations in gastric juice, it does not have a significant difference in the eradication of H. pylori compared with claritromycin.

We conclude that the results of our study showed no significant difference of azithromycin versus claritromycin in the eradication of H. pylori infection in HD patients.


   Acknowledgments Top


This article has been the result of expertism doctoral thesis of the responsible author, Jamshid Vafaeimanesh. This work was supported by grants from Iran's Zanjan University of Medical Sciences. The authors would like to thank Dr. Mirzamohammadi for his help in the analysis of this design.

 
   References Top

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15.Bertoni G, Sassatelli R, Nigrisoli E, et al. Triple therapy with Azithromycin, omeprazole, and amoxicillin is highly effective in the eradication of Helicobacter pylori: A con­trolled trial versus omeprazole plus amoxicillin. Am J Gastroenterol 1996;91:258-63.  Back to cited text no. 15
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18.Chey W, Fisher L, Barnett J, 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. 18
    
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24.Ghaempanah AM, Gasemian Safaii H, Nazarian M, Vafaeemanesh J, Relating H pylori infection with adenocarcinoma and chronic active gastritis and peptic ulcer in the Zanjan (Iran) region. 2nd International and 7th National Congress on Quality Improvement In Clinical Labratories. Tehran-Iran 20-23 April 2009.  Back to cited text no. 24
    
25.Karari EM, Lule GN, McLigeyo SO, Amayo EO. Endoscopic findings and the prevalence of Helicobacter pylori in chronic renal failure patients with dyspepsia. East Afr Med J 2000;77:406-9.  Back to cited text no. 25
    
26.al-Assi MT, Genta RM, Karttunen TJ, Cole RA, Graham DY. Azithromycin triple therapy for Helicobacter pylori infection: Azithro-mycin, tetracycline, and bismuth. Am J Gastroenterol 1995;90:403-5.  Back to cited text no. 26
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27.Laurent J, Mégraud F, Fléjou JF, Caekaert A, Barthélemy P. A randomized comparison of four omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 2001;15:1787-93.  Back to cited text no. 27
    
28.Trautmann M, Riediger C, Möricke A, Vogt K, Bohr U, Glasbrenner B. Combined activity of Azithromycin and lansoprazole against Helicobacter pylori. Helicobacter 1999;4:113-20.  Back to cited text no. 28
    
29.Krichhoff RM, Laufen H, Schäcke 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. 29
    
30.Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the develop­ment of gastric cancer. N Eng J Med 2001; 345:784-9.  Back to cited text no. 30
    

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Correspondence Address:
Jamshid Vafaeimanesh
Clinical Research Development Center, Qom University of Medical Sciences, Qom
Iran
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DOI: 10.4103/1319-2442.124486

PMID: 24434382

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