{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:56:13Z","timestamp":1783587373953,"version":"3.55.0"},"reference-count":50,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,3]]},"abstract":"<jats:p><jats:italic>Helicobacter pylori<\/jats:italic> antibiotic susceptibility in the Dominican Republic has not been monitored. We assessed <jats:italic>H. pylori<\/jats:italic> antibiotic susceptibility in the Dominican Republic, and analyzed <jats:italic>H. pylori<\/jats:italic> 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\u2013based sequencing was used to assess <jats:italic>gyrA<\/jats:italic>, <jats:italic>gyrB<\/jats:italic>, <jats:italic>rdxA<\/jats:italic>, <jats:italic>frxA<\/jats:italic>, and 23S rRNA mutations; next-generation sequencing was used to identify other metronidazole resistance\u2013associated genes. Among 64 <jats:italic>H. pylori<\/jats:italic> 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 <jats:italic>rdxA<\/jats:italic> and <jats:italic>frxA<\/jats:italic> mutations in metronidazole-resistant strains, but no synergistic effect was apparent. We revealed novel mutations in <jats:italic>dppA<\/jats:italic>, <jats:italic>dppB<\/jats:italic>, <jats:italic>fdxA<\/jats:italic>, and <jats:italic>fdxB<\/jats:italic>, irrespective of <jats:italic>rdxA<\/jats:italic> and <jats:italic>frxA<\/jats:italic> mutations. Novel mutations at Ser-14 of <jats:italic>trx1<\/jats:italic> and Arg-221 of <jats:italic>dapF<\/jats:italic> were associated with different levels of metronidazole resistance. Most levofloxacin-resistant strains had a substitution at Asn-87 of <jats:italic>gyrA<\/jats:italic>, including the strain with the highest levofloxacin resistance, whereas only three substitutions were found at Ser-479 of <jats:italic>gyrB<\/jats:italic> 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 <jats:italic>H. pylori<\/jats:italic> infection.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0729","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T01:40:26Z","timestamp":1487036426000},"page":"1050-1059","source":"Crossref","is-referenced-by-count":14,"title":["Clarithromycin-Based Triple Therapy is Still Useful as an Initial Treatment for Helicobacter pylori Infection in the Dominican Republic"],"prefix":"10.4269","volume":"96","author":[{"given":"Muhammad","family":"Miftahussurur","sequence":"first","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan."},{"name":"Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas."},{"name":"Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital-Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modesto","family":"Cruz","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Parasitology, Faculty of Science, Autonomous University of Santo Domingo, Santo Domingo, Dominican Republic."},{"name":"Department of Biomedical Research, National Institute of Medicine and Diagnostic Imaging, Santo Domingo, Dominican Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phawinee","family":"Subsomwong","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Jim\u00e9nez Abreu","sequence":"additional","affiliation":[{"name":"Dominican\u2013Japanese Digestive Disease Center, Dr. Luis E. Aybar Health and Hygiene City, Santo Domingo, Dominican Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Hosking","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Parasitology, Faculty of Science, Autonomous University of Santo Domingo, Santo Domingo, Dominican Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Akada","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan."},{"name":"Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"ref1","series-title":"J Gastroenterol Hepatol","first-page":"1587","article-title":"Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection","volume":"24","author":"Fock","year":"2009"},{"key":"ref2","series-title":"Gut","first-page":"646","article-title":"Management of Helicobacter pylori infection: the Maastricht IV\/ Florence Consensus Report","volume":"61","author":"Malfertheiner","year":"2012"},{"key":"ref3","series-title":"World J Gastroenterol","first-page":"9898","article-title":"Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance","volume":"20","author":"Papastergiou","year":"2014"},{"key":"ref4","series-title":"Molecules","first-page":"6068","article-title":"Appropriate first-line regimens to combat Helicobacter pylori antibiotic resistance: an Asian perspective","volume":"20","author":"Miftahussurur","year":"2015"},{"key":"ref5","series-title":"BMC Gastroenterol","first-page":"164","article-title":"Low Helicobacter pylori primary resistance to clarithromycin in gastric biopsy specimens from dyspeptic patients of a city in the interior of Sao Paulo, Brazil","volume":"13","author":"Suzuki","year":"2013"},{"key":"ref6","series-title":"Helicobacter","first-page":"227","article-title":"Identification of a 23S rRNA gene mutation in clarithromycin-resistant Helicobacter pylori","volume":"1","author":"Stone","year":"1996"},{"key":"ref7","series-title":"Mol Microbiol","first-page":"383","article-title":"Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase","volume":"28","author":"Goodwin","year":"1998"},{"key":"ref8","series-title":"J Bacteriol","first-page":"5082","article-title":"Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori","volume":"182","author":"Jeong","year":"2000"},{"key":"ref9","series-title":"Antimicrob Agents Chemother","first-page":"2343","article-title":"Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing","volume":"59","author":"Binh","year":"2015"},{"key":"ref10","series-title":"World J Gastroenterol","first-page":"1847","article-title":"Screening for metronidazole-resistance associated gene fragments of H. pylori by suppression subtractive hybridization","volume":"13","author":"Li","year":"2007"},{"key":"ref11","series-title":"Biochem Biophys Res Commun","first-page":"785","article-title":"Isolation of a genetic locus associated with metronidazole resistance in Helicobacter pylori","volume":"236","author":"Chang","year":"1997"},{"key":"ref12","series-title":"J Bacteriol","first-page":"2927","article-title":"The fdxA ferredoxin gene can down-regulate frxA nitroreductase gene expression and is essential in many strains of Helicobacter pylori","volume":"185","author":"Mukhopadhyay","year":"2003"},{"key":"ref13","series-title":"Antimicrob Agents Chemother","first-page":"2133","article-title":"Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori","volume":"44","author":"Kwon","year":"2000"},{"key":"ref14","series-title":"J Bacteriol","first-page":"1961","article-title":"Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization","volume":"183","author":"Baker","year":"2001"},{"key":"ref15","series-title":"Curr Drug Ther","first-page":"190","article-title":"Who's winning the war? Molecular mechanisms of antibiotic resistance in Helicobacter pylori","volume":"3","author":"Jones","year":"2008"},{"key":"ref16","series-title":"Helicobacter","first-page":"36","article-title":"Fluoroquinolone resistance in Helicobacter pylori: role of mutations at position 87 and 91 of GyrA on the level of resistance and identification of a resistance conferring mutation in GyrB","volume":"17","author":"Rimbara","year":"2012"},{"key":"ref17","series-title":"Am J Gastroenterol","first-page":"485","article-title":"The problem of Helicobacter pylori resistance to antibiotics: a systematic review in Latin America","volume":"109","author":"Camargo","year":"2014"},{"key":"ref18","series-title":"J Med Microbiol","first-page":"1189","article-title":"Virulence genes of Helicobacter pylori in the Dominican Republic","volume":"63","author":"Shiota","year":"2014"},{"key":"ref19","series-title":"Gut","first-page":"772","article-title":"Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report","volume":"56","author":"Malfertheiner","year":"2007"},{"key":"ref20","series-title":"Gut","first-page":"6","article-title":"Management of Helicobacter pylori infection: the Maastricht V\/Florence Consensus Report","volume":"66","author":"Malfertheiner","year":"2017"},{"key":"ref21","series-title":"J Antimicrob Chemother","first-page":"793","article-title":"Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates","volume":"46","author":"Kwon","year":"2000"},{"key":"ref22","series-title":"World J Gastroenterol","first-page":"2272","article-title":"Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains","volume":"16","author":"Wang","year":"2010"},{"key":"ref23","series-title":"J Dig Dis","first-page":"101","article-title":"Clarithromycin resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Malaysia","volume":"11","author":"Ho","year":"2010"},{"key":"ref24","series-title":"J Gastrointestin Liver Dis","first-page":"409","article-title":"Worldwide H. pylori antibiotic resistance: a systematic review","volume":"19","author":"De Francesco","year":"2010"},{"key":"ref25","series-title":"FEBS J","first-page":"4306","article-title":"Structure of RdxA: an oxygen-insensitive nitroreductase essential for metronidazole activation in Helicobacter pylori","volume":"279","author":"Martinez-Julvez","year":"2012"},{"key":"ref26","series-title":"J Antimicrob Chemother","first-page":"753","article-title":"The role of the rdxA gene in the evolution of metronidazole resistance in Helicobacter pylori","volume":"43","author":"Jenks","year":"1999"},{"key":"ref27","series-title":"Antimicrob Agents Chemother","first-page":"2609","article-title":"DNA sequence analysis of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant clinical Helicobacter pylori isolates","volume":"45","author":"Kwon","year":"2001"},{"key":"ref28","series-title":"Gut","first-page":"34","article-title":"Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption","volume":"62","author":"Megraud","year":"2013"},{"key":"ref29","series-title":"Expert Rev Anti Infect Ther","first-page":"59","article-title":"Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents","volume":"8","author":"Boyanova","year":"2010"},{"key":"ref30","series-title":"Rev Panam Salud Publica","first-page":"219","article-title":"Trends in antibiotic utilization in eight Latin American countries, 1997\u20132007","volume":"27","author":"Wirtz","year":"2010"},{"key":"ref31","series-title":"J Clin Microbiol","first-page":"397","article-title":"Real-time PCR assay for rapid and accurate detection of point mutations conferring resistance to clarithromycin in Helicobacter pylori","volume":"41","author":"Oleastro","year":"2003"},{"key":"ref32","series-title":"World J Gastroenterol","first-page":"8168","article-title":"How antibiotic resistances could change Helicobacter pylori treatment: a matter of geography?","volume":"19","author":"Ierardi","year":"2013"},{"key":"ref33","series-title":"Ann Intern Med","first-page":"94","article-title":"Clarithromycin-resistant genotypes and eradication of Helicobacter pylori","volume":"144","author":"De Francesco","year":"2006"},{"key":"ref34","series-title":"J Antimicrob Chemother","first-page":"47","article-title":"Amoxycillin tolerance in Helicobacter pylori","volume":"43","author":"Dore","year":"1999"},{"key":"ref35","series-title":"J Gastroenterol Hepatol","first-page":"981","article-title":"Antibiotic susceptibility of Helicobacter pylori in the Chinese population","volume":"16","author":"Yakoob","year":"2001"},{"key":"ref36","series-title":"J Gastroenterol Hepatol","first-page":"720","article-title":"Resistance rate to antibiotics of Helicobacter pylori isolates in eastern Taiwan","volume":"22","author":"Hu","year":"2007"},{"key":"ref37","series-title":"J Clin Gastroenterol","first-page":"683","article-title":"Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea","volume":"40","author":"Kim","year":"2006"},{"key":"ref38","series-title":"Gut","first-page":"1374","article-title":"H. pylori antibiotic resistance: prevalence, importance, and advances in testing","volume":"53","author":"Megraud","year":"2004"},{"key":"ref39","series-title":"World J Gastroenterol","first-page":"5746","article-title":"Antimicrobial susceptibility of Helicobacter pylori strains isolated from patients in Shiraz, southern Iran","volume":"16","author":"Farshad","year":"2010"},{"key":"ref40","series-title":"Lancet","first-page":"905","article-title":"Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial","volume":"377","author":"Malfertheiner","year":"2011"},{"key":"ref41","series-title":"PLoS One","first-page":"e101481","article-title":"Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur","volume":"9","author":"Teh","year":"2014"},{"key":"ref42","series-title":"J Bacteriol","first-page":"1454","article-title":"Molecular cloning, characterization, and chromosomal localization of dapF, the Escherichia coli gene for diaminopimelate epimerase","volume":"169","author":"Richaud","year":"1987"},{"key":"ref43","series-title":"Int J Biochem Cell Biol","first-page":"143","article-title":"Oxidases and reductases are involved in metronidazole sensitivity in Helicobacter pylori","volume":"33","author":"Trend","year":"2001"},{"key":"ref44","series-title":"Helicobacter","first-page":"157","article-title":"Systematic review and meta-analysis: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics in Helicobacter pylori eradication","volume":"10","author":"Gisbert","year":"2005"},{"key":"ref45","series-title":"Therap Adv Gastroenterol","first-page":"331","article-title":"Second-line rescue therapy of Helicobacter pylori infection","volume":"2","author":"Gisbert","year":"2009"},{"key":"ref46","series-title":"Mem Inst Oswaldo Cruz","first-page":"741","article-title":"Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?","volume":"101","author":"Andrade","year":"2006"},{"key":"ref47","series-title":"Am J Gastroenterol","first-page":"1808","article-title":"American College of Gastroenterology guideline on the management of Helicobacter pylori infection","volume":"102","author":"Chey","year":"2007"},{"key":"ref48","series-title":"Antimicrob Agents Chemother","first-page":"1538","article-title":"Gatifloxacin resistance and mutations in gyrA after unsuccessful Helicobacter pylori eradication in Japan","volume":"50","author":"Nishizawa","year":"2006"},{"key":"ref49","series-title":"Antimicrob Agents Chemother","first-page":"550","article-title":"Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France","volume":"56","author":"Garcia","year":"2012"},{"key":"ref50","series-title":"World J Gastroenterol","first-page":"6400","article-title":"Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype","volume":"20","author":"Sugimoto","year":"2014"}],"container-title":["The American Society of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/96\/5\/article-p1050.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/96\/5\/article-p1050.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/96\/5\/article-p1050.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T22:32:56Z","timestamp":1723069976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/96\/5\/article-p1050.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,3]]},"references-count":50,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.16-0729","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,3]]}}}