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

• DOI: 10.4269/ajtmh.16-0729
• Publication Date: 2017-02-14T01:40:26Z
• Authors: Muhammad Miftahus...; Modesto Cruz; Phawinee Subsomwong; José A. Jiménez A...; Celso Hosking; Hiroyuki Nagashima; Junko Akada; Yoshio Yamaoka
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; 610; Levofloxacin; Microbial Sensitivity Tests; Helicobacter Infections; 03 medical and health sciences; R735-854 Medical education. Medical schools. Research; Clarithromycin; Metronidazole; Drug Resistance, Bacterial; Humans; Aged; Aged, 80 and over; Helicobacter pylori; Dominican Republic; Amoxicillin; High-Throughput Nucleotide Sequencing; R5-920 Medicine (General); Anti-Bacterial Agents; 3. Good health; Genes, Bacterial; Drug Therapy, Combination; Female

Helicobacter pylori antibiotic susceptibility in the Dominican Republic has not been monitored. We assessed H. pylori antibiotic susceptibility in the Dominican Republic, and analyzed H. pylori 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 gyrA, gyrB, rdxA, frxA, and 23S rRNA mutations; next-generation sequencing was used to identify other metronidazole resistance–associated genes. Among 64 H. pylori 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 rdxA and frxA mutations in metronidazole-resistant strains, but no synergistic effect was apparent. We revealed novel mutations in dppA, dppB, fdxA, and fdxB, irrespective of rdxA and frxA mutations. Novel mutations at Ser-14 of trx1 and Arg-221 of dapF were associated with different levels of metronidazole resistance. Most levofloxacin-resistant strains had a substitution at Asn-87 of gyrA, including the strain with the highest levofloxacin resistance, whereas only three substitutions were found at Ser-479 of gyrB 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 H. pylori infection.