Clarithromycin-Based Triple Therapy is Still Useful as an Initial Treatment for Helicobacter pylori Infection in the Dominican Republic

Abstract

Abstract<i>Helicobacter pylori</i> antibiotic susceptibility in the Dominican Republic has not been monitored. We assessed <i>H. pylori</i> antibiotic susceptibility in the Dominican Republic, and analyzed <i>H. pylori</i> mutations associated with antibiotic resistance. We recruited 158 dyspeptic patients in Santo Domingo and used agar dilution to test susceptibility to five antibiotics. Polymerase chain reaction-based sequencing was used to assess <i>gyrA</i>, <i>gyrB</i>, <i>rdxA</i>, <i>frxA</i>, and 23S rRNA mutations; next-generation sequencing was used to identify other metronidazole resistance-associated genes. Among 64 <i>H. pylori</i> strains isolated, we identified two (3.1%), one (1.6%), and no strains with clarithromycin, amoxicillin, and tetracycline resistance, respectively. Moreover, high frequency of metronidazole resistance (53/64, 82.8%) was observed, whereas levofloxacin resistance is emerging (23/64, 35.9%). We identified many <i>rdxA</i> and <i>frxA</i> mutations in metronidazole-resistant strains, but no synergistic effect was apparent. We revealed novel mutations in <i>dppA</i>, <i>dppB</i>, <i>fdxA</i>, and <i>fdxB</i>, irrespective of <i>rdxA</i> and <i>frxA</i> mutations. Novel mutations at Ser-14 of <i>trx1</i> and Arg-221 of <i>dapF</i> were associated with different levels of metronidazole resistance. Most levofloxacin-resistant strains had a substitution at Asn-87 of <i>gyrA</i>, including the strain with the highest levofloxacin resistance, whereas only three substitutions were found at Ser-479 of <i>gyrB</i> with no synergistic effect. Besides the 23S rRNA A2142G mutation, we observed another mutation at T1958G in both clarithromycin-resistant strains. We confirmed high metronidazole and levofloxacin resistance associated with genetic mutations in the Dominican Republic. However, prevalence of clarithromycin resistance was low, suggesting that standard clarithromycin-based triple therapy remains useful as initial treatment of <i>H. pylori</i> infection.