Antibiotic resistance mechanisms of Helicobacter pylori

Infection with Helicobacter pylori is most frequently associated with gastr itis and peptic ulcer disease. Antimicrobial intervention, together with pr oton pump inhibitors, has become the standard therapy for treating this dis ease. Resistance to clarithromycin and metronidazole, two of the most commo nly used antimicrobials for treatment of H pylori infections, is often asso ciated with treatment failures and relapse of infection. Clarithromycin res istance arises through mutations leading to base changes in 23S ribosomal R NA subunits, while resistance to metronidazole is due to mutations in the r dxA gene, which encodes a novel nitroreductase that is responsible for redu ctive activation of the drug. Products of metronidazole activation are muta genic and can be demonstrated to increase both the mutation frequency and t he frequency at which antibiotic resistance arises in H pylori.