Iranian Journal of Pediatrics Tehran University of Medical Sciences Press ISSN: 1018-4406 EISSN: 2008-2150 Vol. 19, Num. 3, 2009, pp. 244-248

Iranian Journal of Pediatrics, Vol. 19, No. 3, Sept, 2009, pp. 244-248

Success Rate of Furazolidone-Based Triple Therapy for Eradication of Helicobacter Pylori in Children

Mehri Najafi, MD*¹; Ahmad Khodadad, MD¹; Gholamhossein Fallahi, MD;  Fatemeh Farahmand¹, MD; Farzaneh Motamed, MD¹; Mohammad Sobhani¹,MD

1. Department of Pediatrics, Tehran University of Medical Sciences, Tehran, IR Iran

Received: Oct 07, 2008; Final Revision: Jan 08, 2009; Accepted: Mar 07, 2009

Code Number: pe09037

Abstract

Objective: Helicobacter pylori (H. Pylori) is now recognized as a major etiological factor in the pathogenesis of gastritis and peptic ulcer disease. There is concrete evidence that eradication of the bacterium reverses histological gastritis, and results in significant reduction of duodenal and gastric ulcer recurrence. Poor compliance and antibiotic resistance are the main causes for failure of anti H. pylori therapy. In this study we determined efficacy of omeprazole based triple therapy with b.i.d. dosing of furazolidone, amoxicillin for 2 weeks and omeprazole in Iranian children.
Methods: This prospective study included 37 children, in whom H. Pylori infection was diagnosed endoscopically.H.Pylori positive children were treated with a two weeks course of furazoidone (6 mg/kg/day) and amoxicillin (50 mg/kg/day) plus omeprazole (1-2 mg/kg/day). Eradication was assessed by ¹³C UBT.
Findings: Mean age of patients was 10.2 yr (5-15 yr), 25 (67.5%) patients were boys. H. Pylori was eradicated in 34 children (per patient 91.9%, per protocol 86%).Side effects occurred in 3 (8.1%) patients, but these were mild and it was not necessary to discontinue treatment. Three children (8.1%) remained H. pylori positive.
Conclusion: Our study showed that the association of furazolidone plus amoxicillin with a proton-pump inhibitor could be a valuable alternative for eradication of H. Pylori infection in children. It is an effective, affordable treatment that allows good compliance and produces low adverse effect rates.

Key Words: Helicobacter pylori; Furazolidone; Omeprazole triple therapy; Children

Introduction

Helicobacter pylorus is now recognized as a major etiological factor in the pathogenesis of gastritis and peptic ulcer disease ^[1]. There is concrete evidence that eradication of the bacterium reverses histological gastritis, and results in significant reduction of duodenal and gastric ulcer recurrence ^[1].

A recent meta-analysis concluded that recurrent infection is rare when eradication rates exceed 90% ^[2]. Eradication regimens for H. pylori must be effective, safe, with minimal induction of resistance. In Asia, H. pylori eradication is difficult and generally two weeks of treatment is necessary ^[3,4].

Metronidazole resistance is a common problem and clarithromycin is expensive ^[5,6] but H. pylori is sensitive to Furazolidone and reports of resistance have been scarce so far^[6-8]. Furazolidone was effective against H. pylori in Iranian patients and was a good substitute for clarithromycin or metronidazole ^[9,10,11]. In addition to its efficacy, Furazolidone is a relatively inexpensive and easily affordable medication. In many of reports furazolidone consumption for two weeks in adults was associated with adverse reactions such as anorexia, dizziness, urticarial rash, flu-like symptoms, and fever in 5–15% of cases, therefore, limiting its prescription ^[5,9].

The early childhood years are important with regard to exposure to H. pylori infection, with higher rates of acquisition than during the adult years^[12,13]. When selecting a therapy to eradicate H. pylori, duration of treatment and adverse effects should be considered ^[1].

Until recently, the recommended duration of therapy for H. pylori eradication was one to two weeks. In this study we determined efficacy of triple therapy and two antibiotics (furazolidone, and amoxicillin) for 2 weeks.

Subjects and Methods

Children with chronic abdominal pain, hematemesis, and melena between 2.5 and 16 years of age were prospectively recruited during 2006 and 2007.

Children with H. Pylori infection confirmed by endoscopy and pathology entered the study. Patients who had undergone previous H. Pylori eradication therapy prior to the study or had a previous history of severe renal and hepatic disease were excluded from the study.

Upper gastrointestinal endoscopy was carried out after midazolam sedation (0.1 mg per kg). Gastric antral biopsy specimens were taken for histology examination, Giemsa staining and urease testing.

The presence of H. Pylori in histology was accepted as diagnostic for infection. H. Pylori positive children were treated with a two week course of amoxicillin (50 mg/kg/day b.i.d. as syrup or capsule) and furazolidone (6 mg/kg/day b.i.d. as syrup or tablet) plus four weeks omeprazole (1-2 mg/kg/day), and reinvestigated eight to ten weeks after accomplished treatment by urea breath test (¹³C UBT). This test was performed after a fasting period of 6 hours or longer. The patients swallowed capsules containing urea labeled ¹³C (non radioactive) and ¹³C in the expired air was measured 20 minutes later, using an infrared spectrophotometer (IRIS, Dr. Wagner, Bremen, Germany).

The difference between the values obtained at 20 minutes and at baseline was expressed as delta over baseline (DOB %). The cut-off value for negative UBT was less than 2.5 and for positive UBT more than 4.0 δ unit (delta over base).

Children, in whom H. Pylori persisted, were treated successfully with quadruple regimen (omeprazole, amoxicillin, bismuth subcitrate and clarithromycin).

The Ethics Committee of Tehran University of Medical Sciences approved the protocol.  Statistical analysis: Chi-square test or Fisher's exact test was used for qualitative variables and the Student t-test for quantitative variables. SPSS software for Windows version 15 was then used for processing of data. A P-value of less than 0.05 was considered significant.

Findings

Thirty seven children fulfilled inclusion criteria. Their mean age was10.2 years, range 5 to 17 (10.9± 2.5) years and 25 (67.5%) of them were boys. Characteristics of patients and endoscopic findings are shown in Tables 1 and 2.

All 37 children completed treatment protocol combined of amoxicillin and furazulidone and omeprazole. Side effects occurred in three (8.1 %) children: (abdominal pain in two, vomiting, and headache each affected one child), but these were mild and it was not necessary to discontinue treatment.

Overall, the eradication was cleared in 34 of 37 children, giving an eradication rate of 91.9% (95% CI, 83%-98%) in ITT analysis. Three children (8.1%) remained H. pylori positive. All of these persistently H. pylori positive children had cleared from infection by a quadruple therapy (omeprazole, bismuth subcitrate, amoxicillin, clarithro-mycin).

Discussion

Treatment of H. Pylori infection is definitely indicated in children with proven H. Pylori gastritis, but also no ulcer need be treated is still debated. Treatment induces the eventual healing of inflammation and ulceration and significant reduction in the likelihood of developing gastric carcinoma ^[14]. However, after H. Pylori gastritis is diagnosed, the current approach is to treat the patient ^[15].

Triple treatment including a proton pump inhibitor (PPI) and clarithromycin, combined with either amoxicillin or metronidazole has been recommended to treat children with H. pylori infection^[16].

In children all regimens should continue for 7-14 days ^[14]. However antibiotic resistance is increasing, so new therapeutic regimens are needed ^[17,18].

In this study we show that administering furazolidone for 2 weeks b.i.d. plus omeprazole and amoxicillin in a triple anti H. pylori treatment regimen has a high eradication rate (per patient 91.9%, per protocol 86%). One of the great impediments regarding the use of furazolidone is its association with some side effects, reported mainly from adults and studies carried out in Europe ^[9,19]. In our study however, no patient had to interrupt the treatment due to side effects.

The results of H. Pylori treatment in children are different from that in adults. So some authors concluded that treatment recommended for adults may be not suitable for children ^[20]. Bahremand et al, compared a triple therapy (omeprazole, amoxicillin, and clarithromycin) to a quadruple therapy (omeprazole, amoxicilline, metronidazole and bismuth subcitrate for 10 days), in Iranian children with H. pylori infection. The eradication rates were higher in triple versus bismuth quadruple therapy (92% vs. 84%) ^[21].

In the study of Arenz et al^[22] one week esomeprazole–based triple therapy (amoxi-cillin, clarithromycin) was very effective in eradication of H. Pylori in children (92-93%).

The rate of resistance was 9% for clarithromycin and 16% for metronidazole. Triple therapy is more effective than dual therapy ^[23].

In Iranian children the rate of resistance to metronidazole was very high (72-79%), and susce ptibility to amoxicillin was 58% and 75% for clarithromycin ^[24]. In another study from Iran ^[25] the rate of resistance to metronidazole was (54.2%), and there was no resistance to furazolidone. Kawakami et al treated 38 children with omeprazole, clarithromycin and furazolidone for 7 days ^[26]. The rate of success was 84.8% per patient and 73.7% per protocol.

So treatment of H. Pylori in children needs more designed randomized placebo- controlled trials, especially in developing countries^[27]. The high rate of resistance to antibiotics in these countries and also low compliance for drug intake are the main reasons for treatment failure ^[28].

Our limitations: Peptic disease in children is much less than in adults, and also some of the parents are not consent to endoscopy. So gathering sufficient sample is difficult.

Conclusion

Triple omerazole based therapy (OAF) could be a valuable alternative to first line eradication therapy of H. pylori in children. It is an effective, affordable treatment that allows good compliance and produce low adverse effect rates, but further multicenter trials are needed to establish its role in the H. Pylori infection.

Acknowledgment

This study was approved by research committee of Tehran University of Medical Sciences. We thank greatly Mrs. Sadeghie responsible in Radio Isotope Ward of Dr Shareiatee Hospital, and also Mrs. M. Madadie and S. Tafreshie proficient nurses of Children's Medical Center Endoscopy Unit for their unreserved cooperation.

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