TY - JOUR
T1 - Clarithromycin-based triple therapy is still useful as an initial treatment for helicobacter pylori infection in the Dominican Republic
AU - Miftahussurur, Muhammad
AU - Cruz, Modesto
AU - Subsomwong, Phawinee
AU - Abreu, José A.Jiménez
AU - Hosking, Celso
AU - Nagashima, Hiroyuki
AU - Akada, Junko
AU - Yamaoka, Yoshio
N1 - Funding Information:
Financial support: This work was supported in part by grants from the National Institutes of Health (DK62813) and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (25293104, 26640114, 15H02657, and 221S0002) (Yoshio Yamaoka). It was also supported by the Japan Society for the Promotion of Science (JSPS) Institutional Program for Young Researcher Overseas Visits (Yoshio Yamaoka), Strategic Funds for the Promotion of Science and Technology from the Japan Science and Technology Agency (JST) (Yoshio Yamaoka). In addition, it was supported in part by a grant from The National Fund for Innovation and Development of Science and Technology (FONDOCYT) from the Ministry of Higher Education Science and Technology (MESCyT) of the Dominican Republic (2012-2013-2A1-65 and 2015-3A1-182) (Modesto Cruz). Muhammad Miftahussurur was a PhD student and Phawinee Subsomwong is a PhD student supported by The Japanese Government (MEXT) Scholarship Program for 2012 and 2013, respectively.
Publisher Copyright:
Copyright © 2017 by The American Society of Tropical Medicine and Hygiene.
PY - 2017
Y1 - 2017
N2 - 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 levofloxacinresistant 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.
AB - 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 levofloxacinresistant 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.
UR - http://www.scopus.com/inward/record.url?scp=85019055936&partnerID=8YFLogxK
U2 - 10.4269/ajtmh.16-0729
DO - 10.4269/ajtmh.16-0729
M3 - Article
C2 - 28193745
AN - SCOPUS:85019055936
SN - 0002-9637
VL - 96
SP - 1050
EP - 1059
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
IS - 5
ER -