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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 20  |  Issue : 1  |  Page : 67-71

Two nitazoxanide-based quadruple regimens for eradication of Helicobacter pylori infection: a single-center randomized controlled trial


Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Assiut, Egypt

Date of Submission28-Jun-2021
Date of Decision30-Aug-2021
Date of Acceptance30-Aug-2021
Date of Web Publication4-Mar-2022

Correspondence Address:
MD Amro M Hassan
Assistant Professor of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Assiut, ZIP/Postal Code: 71524
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/azmj.azmj_74_21

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  Abstract 


Background and aim Eradication of Helicobacter pylori becomes an ongoing challenge worldwide because eradication rates of H. pylori are declining to less than 60% in some countries. As there is no acceptable definite long-standing used therapeutic regimen for H. pylori, clinicians are doing their best to find new regimens to improve eradication rates of H. pylori. Nitazoxanid and fluoroquinolones, including moxifloxacin and levofloxacin, have been used in treatment of H. pylori. The study aimed to assess and compare the efficacy of two nitazoxanide-based quadruple regimens in treatment of patients infected with H. pylori.
Patients and methods This prospective randomized controlled trial was conducted on 100 patients diagnosed to be infected by H. pylori by stool antigen test (one-step H. pylori Antigen test Device). They were randomized into two groups: group 1: 50 patients were treated for 14 days with quadruple therapy, including nitazoxanide, moxifloxacin, omeprazole, and doxycycline; and group 2: 50 patients were treated for 14 days with quadruple therapy, including nitazoxanide, levofloxacin, omeprazole, and doxycycline. Eradication of H. pylori was assessed 4 weeks after the end of treatment by stool antigen test (one-step H. pylori Antigen test Device).
Results Eradication rate of H. pylori infection was higher in patients treated with nitazoxanide–moxifloxacin-based quadruple therapy 37 (74%) than in patients treated with nitazoxanide–levofloxacin-based quadruple therapy 32 (64%), but there were no significant differences between the studied groups with P value (P<0.28). By subgroup analysis of eradication rate among anemic and nonanemic patients treated by nitazoxanide–moxifloxacin and nitazoxanide–levofloxacin-based quadruple therapy, we found that eradication rate was higher in anemic patients 88% and 80% than nonanemic patients 60% and 45%, with significant P values 0.02 and 0.01, respectively.
Conclusions Use of moxifloxacin instead of levofloxacin in the nitazoxanide-based quadruple regimen improves eradication therapy of H. pylori.

Keywords: H. pylori eradication, levofloxacin, moxifloxacin, nitazoxanide, quadruple regimen


How to cite this article:
Hassan AM, Eid K, Eliwa KA, Abdel-Gawad M. Two nitazoxanide-based quadruple regimens for eradication of Helicobacter pylori infection: a single-center randomized controlled trial. Al-Azhar Assiut Med J 2022;20:67-71

How to cite this URL:
Hassan AM, Eid K, Eliwa KA, Abdel-Gawad M. Two nitazoxanide-based quadruple regimens for eradication of Helicobacter pylori infection: a single-center randomized controlled trial. Al-Azhar Assiut Med J [serial online] 2022 [cited 2022 Jun 29];20:67-71. Available from: http://www.azmj.eg.net/text.asp?2022/20/1/67/339077




  Introduction Top


Helicobacter pylori (H. pylori) infection is the most common worldwide chronic bacterial infection; ∼50% of the world was estimated to be infected with H. pylori [1].

H. pylori is treated with proton-pump inhibitor (PPI) and combinations of two or more antimicrobials, taken concomitantly or sequentially over a period of time ranging from 3 to 14 days [2]. Despite there are different treatment regimens, no regimen can achieve 100% cure rate [3].

Antibiotic resistance varies among affected populations in different geographical areas and from one area to another in the same country, which in turn will greatly affect eradication rates of H. pylori [4].

Unfortunately, triple therapy regimen for H. pylori, which includes metronidazole or clarithromycin, is associated with significant increase patterns of resistance and decrease in eradication rate [5],[6],[7].

In regions with increasing resistance to standard triple therapy, quadruple therapy is gaining in popularity [8].

Fluoroquinolones have antimicrobial activity against Gram-positive and Gram-negative bacteria [9],[10]. Levofloxacin and moxifloxacin have been used in treatment of H. pylori and many studies have demonstrated that levofloxacin- and moxifloxacin-based regimens provide excellent first-line therapies and rescue regimens for H. pylori eradication [11],[12],[13].

The aim of the study was to assess the efficacy of moxifloxacin–nitazoxanide versus levofloxacin–nitazoxanide-based quadruple regimen in patients infected with H. pylori.


  Patients and methods Top


This prospective randomized controlled study was designed to assess and compare the efficacy and safety of moxifloxacin versus levofloxacin in nitazoxanide-based quadruple regimen for treatment of patients infected with H. pylori. The study was conducted on 100 patients infected with H. pylori attended to the outpatient clinic of the gastroenterology department at Al-Azhar-Assiut University Hospital from January 2020 to October 2020. The study was done in accordance with the World Medical Association Declaration of Helsinki, revised in 2013, Edinburgh, UK. An approval of Al-Azhar Assuit-Faculty of Medicine Ethical Committee was obtained before the start of the study and informed written consent was signed by every patient enrolled in the study.

Inclusion criteria

Patients infected by H. pylori who were diagnosed by stool antigen test (SAT) (one-step H. pylori Antigen test Device) manufactured by Abon Biopharm, Hangzhou, China and aged more than 18 years were included in the study.

Exclusion criteria

Patients were excluded from the study if they had any of the following: aged less than 18 years, previous exposure to H. pylori eradication therapy, recent intake of antibiotics, PPI, histamine (H2)-receptor blockers, nonsteroidal or anti-inflammatory drugs within 1 month, known allergy to any drug used in the study, gastrointestinal malignancy, active upper gastrointestinal bleeding, recent gastric surgery, renal or hepatic impairment, and pregnant and lactating women.

Investigatory workup

Patients were admitted to the Gastroenterology Department Al-Azhar-Assiut University Hospital. All patients were assessed by full history taking and clinical examination. After a midnight fasting, patients were evaluated by the following laboratory: complete blood count, renal function, and liver functions (aspartate transferase, alanine transferase, serum bilirubin, international normalized ratio, albumin, fasting blood sugar, lipid profile including cholesterol triglycerides, and erythrocyte sedimentation rate). Patients were also assessed by pelv-abdominal ultrasound (US) using a B-mode convex-probe US equipment (Esaote ID, CE0051; Technos, Genoa, Italy) with a 4.5–7 MHz after a midnight fasting.

Eligible patients were randomly divided into two groups: group 1: 50 patients treated for 14 days with Moxifloxacin (moxavidex) 400 mg once daily, Omeprazole (pepzol) 20 mg bid, Nitazoxanide (nanazoxide) 500 mg bid, and Doxycycline (vibramycin) 100 mg bid [moxifloxacin-based quadruple therapy (MOND)]; and group 2: 50 patients treated for 14 days with Levofloxacin (tavanic) 500 mg once daily, Omeprazole (pepzol; Hikma Pharmaceuticals) 20 mg bid, Nitazoxanide (nanazoxide) 500 mg bid, and Doxycycline (vibramycin) 100 mg bid [levofloxacin-based quadruple therapy (LOND)].

All patients were instructed not to use any PPI, H2 blockers, or antibiotic for at least 4 weeks after the end of treatment. All patients were assessed for eradication of H. pylori 4 weeks after the end of treatment by SAT (one-step H. pylori Antigen test Device) manufactured by Abon Biopharm, Hangzhou, China.

Statistical analysis

The collected data were revised, organized, tabulated, and statistically analyzed using Statistical Package for Social Sciences SPSS Version 22 (IBM SPSS Inc., Chicago, Illinois, USA) for Windows 10. Quantitative data were expressed as mean±SD, and qualitative data are expressed as frequency and percentage. Categorical variables of groups were compared using the χ2. Continuous variables of groups were compared by Student’s t-test. P value was considered significant if less than 0.05.


  Results Top


From January 2020 to October 2020, a total of 100 patients diagnosed to be infected by H. pylori by SAT.

The mean age of patients enrolled in the study was 35.74±11.5, 38% of patients were males, and 62% were females, and as regards to demographic data, no significant differences were found between the studied groups. Also, no significant difference between the studied groups as regards to BMI ([Table 1]).
Table 1 Baseline characteristics of the studied groups

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In this study, epigastric pain was present in 52% of patients infected with H. pylori, early satiety in 24%, and heart burn in 21%, while urticaria was present in only 3% of patients and no significant difference between the studied groups as regards to their complaints ([Table 1]).

As regards laboratory parameters that include complete blood count, renal function, liver functions (aspartate transferase, alanine transferase, serum bilirubin, international normalized ratio, albumin, and total protein), fasting blood sugar, total cholesterol, and triglyceride, there were no significant differences between the studied groups concerning [Table 1].

[Table 2] shows that 57% of patients had normal ultrasonographic findings and 43% of patients had fatty liver with no significant differences between the studied groups.
Table 2 Ultrasonographic findings in the studied groups

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Eradication rate of H. pylori infection was higher in patients treated with MOND 37 (74%) than patients treated with LOND 32 (64%) ([Figure 1]), but there were no significant differences between the studied groups with P value (P<0.28) ([Table 3]).
Figure 1 Flowchart of the studied groups.

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Table 3 Helicobacter pylori stool antigen test 4 weeks after treatment in the studied groups

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Subgroup analysis of eradication rate among anemic and nonanemic patients treated by nitazoxanide–moxifloxacin and nitazoxanide–levofloxacin-based quadruple regimen, we found that eradication rate was higher in anemic patients 88% and 80% than nonanemic patients 60% and 45%, with significant P values 0.02 and 0.01, respectively ([Table 4]).
Table 4 Eradication rate among anemic and nonanemic patients treated by MOND and LOND therapy

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In this study, all patients in the studied groups were compliant and adherent to treatment (100.0%) and minor adverse effects were reported in the form of headache, epigastric pain, fatigue, anorexia, nausea, and diarrhea, with no significant difference between the two groups as shown in [Table 5].
Table 5 Adverse effects of treatment in both groups

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  Discussion Top


Eradication of H. pylori is an ongoing challenge worldwide as antibiotic-eradication rates are declining to less than 60% in some countries [14].

In Egypt, the eradication rates of the standard triple therapy (PPI, Clarithromycin and Amoxicillin or Metronidazole) were decreased, as 59.36% in Nile Delta and 62% in Upper Egypt [14],[7]. As the standard triple therapy has low eradication rates, its popularity as first-line eradication therapy of H. pylori in most areas was decreased, consequently alternative regimens become a mandatory issue [15].

Worldwide, there is no acceptable definite long-standing used therapeutic regimen for H. pylori as there is continuous rising of antimicrobial resistance [16].

Levofloxacin is a bactericidal fluoroquinolone and has been used in first-line and salvage regimens for eradication of H. pylori [3]. Also, moxifloxacin is a bactericidal fluoroquinolone and characterized by fast absorption with a bioavailability of 89% and broad penetration through body fluids and tissues [17].

Based on Basu et al. [18] study, our prospective study was done to evaluate levofloxacin-based quadruple regimen proposed by Basu et al. [18] in upper Egyptian patients and to evaluate the efficacy of replacing levofloxacin by moxifloxacin in this regimen.

Our study showed that eradication rate of H. pylori infection was higher in patients treated by moxifloxacin-based quadruple regimen 37 (74%) than in patients treated with levofloxacin-based quadruple therapy 32 (64%).In our study, the eradication rate of H. pylori infection with levofloxacin-based quadruple regimen was lower than the study done by Afifi et al. [19], which showed that the eradication rate of 14-day levofloxacin quadruple therapy was 85.7% and was lower than Basu et al. [18] Study, which showed that the eradication rate of 10-day levofloxacin quadruple therapy was 94.1%. This discrepancy in eradication rate may be due to host genetic factors, genetic variability of H. pylori strains, environmental factors, or antibiotics resistance.

Previous studies had used moxifloxacin for eradication of H. pylori as in Kadhim et al. [20] study that showed eradication rate of 14-day Moxifloxacin-based triple therapy was 80% and Marušić et al. [21] study that showed eradication rate of Bismuth-based quadruple therapy modified with moxifloxacin (bismuth 240 mg bid, pantoprazole 40 mg bid, metronidazole 500 mg bid, and moxifloxacin 400 mg once for 14 days) was 88%.

Also, in Zhang et al. [13] meta-analysis that evaluates the efficacy of moxifloxacin-based triple therapy versus standard triple or quadruple therapy, eradication rate of H. pylori by moxifloxacin-based triple regimens was 79.03 versus 68.33% without moxifloxacin.

As regards Nitazoxanide–moxifloxacin-based quadruple regimen, no previous study used our protocol of Nitazoxanide–moxifloxacin-based quadruple regimen.

In our study, among group 1 treated by MOND regimen, 25 patients were anemic and 25 patients were nonanemic and among group 2 treated by LOND regimen, 26 patients were anemic and 24 were nonanemic. Eradication rate was higher in anemic patients 88% and 80% than nonanemic patients 60% and 45%, with significant P values 0.02 and 0.01, respectively. High eradication rate of H. pylori in anemic patients than nonanemic patients’ needs further studies to explain and clarify this association or cause relationship.

Minor adverse effects were reported in patients treated by moxifloxacin-based quadruple regimen, in the form of headache in 16%, fatigue in 10%, anorexia in 8%, nausea in 16%, epigastric pain in 14%, and diarrhea in 6%, with no significant differences between the two studied groups.

Limitations of our study

Being a single-center trial, small sample size and lack of antibiotic-sensitivity tests before the trial are the main limitations of our study.


  Conclusion Top


Use of Nitazoxanide–moxifloxacin instead of Nitazoxanide–levofloxacin in quadruple regimen improves eradication therapy of H. pylori.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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