Efficacy of a Nitazoxanide Based Regimen for Heliobacter pylori (HP) Eradication

Abstract

Purpose: Clarithromycin and metronidazole are widely utilized as the basis of HP therapy. Unfortunately, increasing microbial resistance to these drugs is one of the most prevalent reasons for HP treatment failures. Nitazoxanide is a thiazolide antibiotic with demonstrated activity against protozoa and anaerobic bacteria including HP. Nitazoxanide exerts its clinical efficacy on HP by interfering with anaerobic energy metabolism at the PFOR enzyme. In vitro data indicates nitazoxanide and tizoxanide (an active metabolite) are highly active against HP, including metronidazole resistant strains. Other studies have demonstrated that nitazoxanide does not possess mutagenic activity, cause DNA fragmentation, or promote cross-resistance with metronidazole. This study evaluates the efficacy and safety of nitazoxanide in conjunction with lansoprazole and amoxicillin in a 7-day regimen for the eradication of HP in previously untreated patients. Methods: An open label study to evaluate the safety and efficacy of a one-week triple drug regimen of nitazoxanide, lansoprazole and amoxicillin in adult patients with treatment naïve HP. All patients had Acute Superficial Gastritis (ASG) and active HP infection. The diagnosis of HP was confirmed by both 14C-Urea Breath Test (14C-UBT) and endoscopic biopsy. Overall 100 patients were enrolled in the study. Patients received nitazoxanide 500 mg BID, lansoprazole 30 mg BID and amoxicillin 1000 mg BID for 7 days. Proton pump inhibitors were discontinued post treatment and therapeutic efficacy was assessed by 14C-UBT performed between the 6th and 8th week after the completion of therapy. Eradication was defined as a negative 14C-UBT, and failure as a positive 14C-UBT at the 6 to 8 week follow-up assessment. Evaluations for safety and tolerability of the regimen were made via interview and physical examination. Results: One hundred patients diagnosed with HP infection and ASG were enrolled in the study (57 female, 43 male) with an average age of 53 years (range 20 to 65 years). Nine patients were excluded for protocol deviation (6 out of 9 patients excluded were 14C-UBT negative at baseline). Eighty-two out of ninety-one evaluable patients (90.1%) were 14C-UBT negative at the 6th to 8th week and were considered cures. Treatment compliance was good, and no major side effects were recorded. Conclusion: A 7-day regimen of nitazoxanide, lansoprazole, and amoxicillin twice daily is effective for the eradication of HP infection in treatment naïve patients. Due to increasing resistance patterns observed with clarithromycin and metronidazole, nitazoxanide may offer a valuable alternative to these medications as a foundation for HP therapy.