Antibiotic Resistance Mechanisms ofHelicobacter pylori

Abstract

Infection withHelicobacter pyloriis most frequently associated with gastritis and peptic ulcer disease. Antimicrobial intervention, together with proton pump inhibitors, has become the standard therapy for treating this disease. Resistance to clarithromycin and metronidazole, two of the most commonly used antimicrobials for treatment ofH pyloriinfections, is often associated with treatment failures and relapse of infection. Clarithromycin resistance arises through mutations leading to base changes in 23S ribosomal RNA subunits, while resistance to metronidazole is due to mutations in therdxAgene, which encodes a novel nitroreductase that is responsible for reductive activation of the drug. Products of metronidazole activation are mutagenic and can be demonstrated to increase both the mutation frequency and the frequency at which antibiotic resistance arises inH pylori.