Antibiotic resistance mechanisms of Helicobacter pylori

Infection with Helicobacter pylori is 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 of H pylori infections, 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 the rdxA gene, 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 in H pylori.