{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:13:19Z","timestamp":1788581599856,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Grant","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The efficacy of fluoroquinolone-based eradication therapy largely depends on the fluoroquinolone resistance of H. pylori. The aim of this study was to investigate the changes in the primary resistance rate of H. pylori to fluoroquinolone and the mechanism of resistance in Korea. A total of 153 strains and 48 strains of H. pylori were isolated at a tertiary hospital in 2005\/2006 and 2017\/2018, respectively. The minimum inhibitory concentrations (MICs) of fluoroquinolone were determined by the serial 2-fold agar dilution method. DNA sequences in the quinolone resistance-determining regions of gyrA\/gyrB were analyzed in resistant strains. Subsequent natural transformation study was performed to determine the association between gyrase mutation and resistance. The resistance rates increased from 19.0% (29\/153) to 43.8% (21\/48) both for levofloxacin and moxifloxacin. The MIC values for resistant strains increased from 2\u20138 \u00b5g\/mL to 4\u201316 \u00b5g\/mL over time. Mutation of gyrA was detected in 93.1% (27\/29) and 100% (21\/21) among the resistant strains in both periods, respectively. A novel Gly-85 mutation of gyrA was found and confirmed to be associated with fluoroquinolone resistance. Fluoroquinolone resistance rate of H. pylori has markedly increased over time in Korea. The resistance is mostly due to the point mutation of gyrA. Fluoroquinolone-containing regimens should be carefully selected in Korea, considering the increasing fluoroquinolone resistance.<\/jats:p>","DOI":"10.3390\/antibiotics9060287","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T08:27:48Z","timestamp":1590654468000},"page":"287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Discovery of a Novel Mutation in DNA Gyrase and Changes in the Fluoroquinolone Resistance of Helicobacter pylori over a 14-Year Period: A Single Center Study in Korea"],"prefix":"10.3390","volume":"9","author":[{"given":"Su Yeon","family":"Rhie","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Health Promotion Center, Samsung Medical Center, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-8920","authenticated-orcid":false,"given":"Jae Yong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Seop","family":"Shin","sequence":"additional","affiliation":[{"name":"MD Healthcare Inc., Seoul 03923, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-6697","authenticated-orcid":false,"given":"Beom Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-9404","authenticated-orcid":false,"given":"Jae Gyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"NIH Consensus Conference (1994). Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA, 272, 65\u201369.","DOI":"10.1001\/jama.272.1.65"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1128\/JCM.42.10.4856-4858.2004","article-title":"Antimicrobial Susceptibility of Helicobacter pylori Strains Isolated in Bangladesh","volume":"42","author":"Nahar","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1097\/MEG.0b013e3283643491","article-title":"Antibiotic susceptibility of Helicobacter pylori in central Germany and its relationship with the number of eradication therapies","volume":"25","author":"Selgrad","year":"2013","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1136\/gut.2009.192757","article-title":"Helicobacter pylori treatment in the era of increasing antibiotic resistance","volume":"59","author":"Graham","year":"2010","journal-title":"Gut"},{"key":"ref_5","first-page":"34","article-title":"On behalf of the Study Group participants Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption","volume":"62","author":"Coenen","year":"2012","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2016-312288","article-title":"Management of Helicobacter pylori infection\u2014The Maastricht V\/Florence Consensus Report","volume":"66","author":"Malfertheiner","year":"2016","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1365-2036.2005.02522.x","article-title":"A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses","volume":"22","author":"Gatta","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tai, W.-C., Lee, C.-H., Chiou, S.-S., Kuo, C.-M., Liang, C.-M., Lu, L.-S., Chiu, C.-H., Wu, K.-L., Chiu, Y.-C., and Hu, T.-H. (2014). The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105822"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/nyas.12830","article-title":"Mechanisms of drug resistance: Quinolone resistance","volume":"1354","author":"Hooper","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3164\/jcbn.08-220R","article-title":"Quinolone-Based Third-Line Therapy for Helicobacter pylori Eradication","volume":"44","author":"Nishizawa","year":"2009","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/apt.13497","article-title":"Review article: The global emergence of Helicobacter pylori antibiotic resistance","volume":"43","author":"Thung","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jaka, H., R\u00fcttgerodt, N., Bohne, W., Mueller, A., Gross, U., Kasang, C., and Mshana, S. (2019). Helicobacter pylori Mutations Conferring Resistance to Fluoroquinolones and Clarithromycin among Dyspeptic Patients Attending a Tertiary Hospital, Tanzania. Can. J. Gastroenterol. Hepatol., 2019.","DOI":"10.1155\/2019\/8481375"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3346\/jkms.2014.29.5.704","article-title":"Meta-Analysis of First-Line Triple Therapy for Helicobacter pylori Eradication in Korea: Is It Time to Change?","volume":"29","author":"Gong","year":"2014","journal-title":"J. Korean Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, J.G., Kim, J.J., Lee, Y.C., Choi, I.J., Yoon, S.M., Sung, J.K., Kim, S.W., Kim, H.S., Jeon, S.W., and Lee, J.Y. (2019). Su1283 \u2013 Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy in First-Line Treatment of Helicobacter Pylori Infection: A Nationwide Randomized Trial in Korea. Gastroenterology, 156.","DOI":"10.1016\/S0016-5085(19)38208-3"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.gastro.2019.04.011","article-title":"Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics","volume":"157","author":"Moss","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_16","first-page":"19","article-title":"The efficacy of levofloxacin based triple therapy for Helicobacter pylori eradication","volume":"48","author":"Lee","year":"2006","journal-title":"Korean J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3346\/jkms.2011.26.6.785","article-title":"Efficacy of Levofloxacin and Rifaximin based Quadruple Therapy in Helicobacter pylori Associated Gastroduodenal Disease: A Double-Blind, Randomized Controlled Trial","volume":"26","author":"Choi","year":"2011","journal-title":"J. Korean Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.5009\/gnl16099","article-title":"Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease","volume":"11","author":"Lim","year":"2016","journal-title":"Gut Liver"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.3748\/wjg.v18.i40.5669","article-title":"Levofloxacin\/amoxicillin-based schemes vs quadruple therapy for Helicobacter pylori eradication in second-line","volume":"18","author":"Fini","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Ahn, J.Y., Choi, K.D., Jung, H.-Y., Kim, J.M., Baik, G.H., Kim, B., Park, J.C., Jung, H., and Cho, S.J. (2019). Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study. Helicobacter, 24.","DOI":"10.1111\/hel.12592"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1086\/510074","article-title":"The Relationship between Previous Fluoroquinolone Use and Levofloxacin Resistance in Helicobacter pylori Infection","volume":"44","author":"Carothers","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/jac\/dki334","article-title":"Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patients","volume":"56","author":"Kim","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1128\/AAC.47.12.3942-3944.2003","article-title":"Single and Double Mutations in gyrA but Not in gyrB Are Associated with Low- and High-Level Fluoroquinolone Resistance in Helicobacter pylori","volume":"47","author":"Tankovic","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7629","DOI":"10.1128\/AAC.01467-15","article-title":"High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of other Fluoroquinolones","volume":"59","author":"Lee","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1128\/AAC.39.1.107","article-title":"Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin-resistant mutants of Helicobacter pylori","volume":"39","author":"Moore","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1440-1746.2011.06874.x","article-title":"Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance","volume":"27","author":"Chung","year":"2012","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1523-5378.2011.00840.x","article-title":"Mutations of Helicobacter pylori Associated with Fluoroquinolone Resistance in Korea","volume":"16","author":"Lee","year":"2011","journal-title":"Helicobacter"},{"key":"ref_28","first-page":"9","article-title":"Primary Levofloxacin-Resistance and gyrA\/B Mutations among Helicobacter pylori in Japan","volume":"11","author":"Miyachi","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Saeed, A., Bosch, A., Bettiol, M., Gonz\u00e1lez, D.N., Erben, M.F., and Lamberti, Y. (2018). Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species. Molecules, 23.","DOI":"10.3390\/molecules23051158"},{"key":"ref_30","first-page":"208","article-title":"Synthesis and in vitro Selective anti-Helicobacter pylori Activity of N-Substituted-2-oxo-2H-1-benzopyran-3-carboxamides","volume":"37","author":"Bizzarri","year":"2006","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5137","DOI":"10.1093\/nar\/20.19.5137","article-title":"DNA diversity among clinical isolates of Helicobacter pylori detected by PCR-based RAPD fingerprinting","volume":"20","author":"Akopyanz","year":"1992","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/j.1523-5378.2005.00316.x","article-title":"Isogenic Variation of Helicobacter pylori Strain Resulting in Heteroresistant Antibacterial Phenotypes in a Single Host In Vivo","volume":"10","author":"Lee","year":"2005","journal-title":"Helicobacter"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1128\/AAC.48.12.4843-4847.2004","article-title":"Distribution of Antibiotic MICs for Helicobacter pylori Strains over a 16-Year Period in Patients from Seoul, South Korea","volume":"48","author":"Kim","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","unstructured":"National Committee for Clinical Laboratory Standards (NCCLS) (2002). Performance Standards for Antimicrobial Susceptibility Testing: Twelfth Informational Supplement, Clinical and Laboratory Standards Institute."},{"key":"ref_35","first-page":"470","article-title":"Antimicrobial resistance rate of Helicobacter pylori isolates and detection of mechanism of clarithromycin resistance","volume":"61","author":"Kim","year":"2001","journal-title":"Korean J. Med."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/6\/287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:33:15Z","timestamp":1760175195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/6\/287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["antibiotics9060287"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics9060287","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]}}}