Review

Increasing trend of metronidazole resistance in the treatment of Helicobacter pylori infection:  A global challenge

Novosti Buta¹, Nicoline F. Tanih¹ and Roland N. Ndip^1,2*.

¹Microbial Pathogenicity and Molecular Epidemiology Research Group, Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Fort Hare, P/Bag X1314, Alice 5700, South Africa.

²Department of Biochemistry and Microbiology, Faculty of Science, University of Buea, Box 63, Buea, Cameroon.

*Corresponding author. E-mail: rndip@ufh.ac.za or ndip3@yahoo.com. Tel: +27 782696191. Fax: +27 86624759.

Abbreviations: MALT, Mucosa-associated lymphoid tissue; Mtz, metronidazole; PPIs, proton pump inhibitors; MIC, minimum inhibitory concentration; CLSI, clinical laboratory standard institute; Mtz^s, Mtz sensitive; Mtz_R, Mtz resistant.

Accepted 29 January, 2010

   Abstract

Helicobacter pylori are gram negative spiral bacteria that colonize the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Antibiotic resistance is an ever increasing problem with the treatment of most microbial infections including H. pylori; and has become a growing problem worldwide with the eradication of this organism. In recent years, several treatment regimens have been proposed for H. pylori eradication. However, the only conditions for which such treatment is strongly recommended on the basis of unequivocal supporting evidence are peptic ulcer disease and low grade gastric MALT lymphoma. Success of antimicrobial regimens for H. pylori eradication depends on patient compliance and lack of antimicrobial resistance. Metronidazole (Mtz) containing regimens have been shown to limit effectiveness because of increasing prevalence of resistance to this drug.  A high prevalence (> 90%) of Mtz resistance in H. pylori has been reported especially in developing countries. Mtz resistance may be mediated through an inability of Mtz-resistant strains to remove oxygen from the site of Mtz reduction, thereby preventing Mtz activation.  This has been attributed to a mutation on the frxA and/or rdxA genes resulting in strains of the organism with defective nitro-reductases coded by these genes. Infection by Mtz or amoxicillin resistant strains is an important factor leading to treatment failure; subjecting all H. pylori clinical isolates to susceptibility testing most especially to Mtz is recommended. If not possible, a program to survey the prevalence of resistance should be implemented in a given area or population. This increasing emergence of antimicrobial resistance in H. pylori treatment posses serious public health problems and is therefore necessary that new drug regimens be examined.

Key words: Helicobacter pylori, drug resistance, metronidazole, gene mutations, public health.