Update on fluoroquinolone resistance in Helicobacter pylori : new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility
Abstract Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly mark...
Gespeichert in:
| Veröffentlicht in: | International journal of antimicrobial agents 2007-04, Vol.29 (4), p.389-396 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 396 |
|---|---|
| container_issue | 4 |
| container_start_page | 389 |
| container_title | International journal of antimicrobial agents |
| container_volume | 29 |
| creator | Cattoir, Vincent Nectoux, Juliette Lascols, Christine Deforges, Lionel Delchier, Jean-Charles Megraud, Francis Soussy, Claude-James Cambau, Emmanuelle |
| description | Abstract Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004–2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC50 = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a ‘test and treat’ strategy that can confidently rely on QRDR gyrA sequencing. |
| doi_str_mv | 10.1016/j.ijantimicag.2006.11.007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70247684</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0924857906004778</els_id><sourcerecordid>20294543</sourcerecordid><originalsourceid>FETCH-LOGICAL-c491t-32a61d7fd8238b95be3fe21288db857dd6301093c490c3783d94fa16fa57d5db3</originalsourceid><addsrcrecordid>eNqNks1u1DAUhSMEokPhFZBZwG4G_2TywwKpGgFFqsQCurYc-2bmDo4dbKdVXosnxNGM1IoNrLzwd-49OucWxRtGN4yy6v1xg0flEg6o1X7DKa02jG0orZ8UK9bUfF23TDwtVrTl5brZ1u1F8SLGI6VsK8rt8-KC1YIK0fJV8ft2NCoB8Y70dvLB_5rQeesdkAARY1JOA0FHrsGi9p3SCQIZZ-sDkg_EwT0ZpqQSeheJBWXQ7Unyj8XKGdJjiIkYiDrguMDE90SR_RyuyOjtPPgwHjAORMXoNWZHhtxjOpDDPEKIU9SQZR1aTPPL4lmvbIRX5_eyuP386cfuen3z7cvX3dXNWpctS2vBVcVM3ZuGi6Zrtx2IHjjjTWO6nIkxlaCMtiLTVIu6EaYte8WqXuXPrenEZfHuNHdcUoGY5IDZh7XKgZ-irCkv66op_wlyyttyW4oMtidQBx9jgF6OAQcVZsmoXJqVR_moWbk0KxmTudmsfX1eMnUDmAflucoMvD0DKmpl-5DDx_jANRWr847M7U4c5OzuEIKMGiEXZTCATtJ4_C87H_-aoi26jNmfMEM8-im4XI5kMnJJ5fflFJdLpBWlZZ3T_gOivOIJ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20294543</pqid></control><display><type>article</type><title>Update on fluoroquinolone resistance in Helicobacter pylori : new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Cattoir, Vincent ; Nectoux, Juliette ; Lascols, Christine ; Deforges, Lionel ; Delchier, Jean-Charles ; Megraud, Francis ; Soussy, Claude-James ; Cambau, Emmanuelle</creator><creatorcontrib>Cattoir, Vincent ; Nectoux, Juliette ; Lascols, Christine ; Deforges, Lionel ; Delchier, Jean-Charles ; Megraud, Francis ; Soussy, Claude-James ; Cambau, Emmanuelle</creatorcontrib><description>Abstract Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004–2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC50 = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a ‘test and treat’ strategy that can confidently rely on QRDR gyrA sequencing.</description><identifier>ISSN: 0924-8579</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2006.11.007</identifier><identifier>PMID: 17303392</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>Amino Acid Sequence ; Anti-Bacterial Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Bacterial diseases ; Bacterial diseases of the digestive system and abdomen ; Biological and medical sciences ; Ciprofloxacin - pharmacology ; DNA gyrase ; DNA Gyrase - drug effects ; DNA Gyrase - genetics ; Drug Resistance, Bacterial - genetics ; Fluoroquinolones - pharmacology ; Fluoroquinolones - therapeutic use ; gyrA polymorphism ; Helicobacter Infections - drug therapy ; Helicobacter Infections - microbiology ; Helicobacter pylori ; Helicobacter pylori - drug effects ; Helicobacter pylori - genetics ; Human bacterial diseases ; Humans ; Infectious Disease ; Infectious diseases ; Medical sciences ; Microbial Sensitivity Tests ; Molecular diagnosis ; Molecular Sequence Data ; Mutation ; Pharmacology. Drug treatments ; Polymorphism, Genetic ; QRDR ; Quinolones</subject><ispartof>International journal of antimicrobial agents, 2007-04, Vol.29 (4), p.389-396</ispartof><rights>Elsevier B.V. and the International Society of Chemotherapy</rights><rights>2006 Elsevier B.V. and the International Society of Chemotherapy</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-32a61d7fd8238b95be3fe21288db857dd6301093c490c3783d94fa16fa57d5db3</citedby><cites>FETCH-LOGICAL-c491t-32a61d7fd8238b95be3fe21288db857dd6301093c490c3783d94fa16fa57d5db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0924857906004778$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18617101$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17303392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cattoir, Vincent</creatorcontrib><creatorcontrib>Nectoux, Juliette</creatorcontrib><creatorcontrib>Lascols, Christine</creatorcontrib><creatorcontrib>Deforges, Lionel</creatorcontrib><creatorcontrib>Delchier, Jean-Charles</creatorcontrib><creatorcontrib>Megraud, Francis</creatorcontrib><creatorcontrib>Soussy, Claude-James</creatorcontrib><creatorcontrib>Cambau, Emmanuelle</creatorcontrib><title>Update on fluoroquinolone resistance in Helicobacter pylori : new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>Abstract Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004–2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC50 = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a ‘test and treat’ strategy that can confidently rely on QRDR gyrA sequencing.</description><subject>Amino Acid Sequence</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Bacterial diseases</subject><subject>Bacterial diseases of the digestive system and abdomen</subject><subject>Biological and medical sciences</subject><subject>Ciprofloxacin - pharmacology</subject><subject>DNA gyrase</subject><subject>DNA Gyrase - drug effects</subject><subject>DNA Gyrase - genetics</subject><subject>Drug Resistance, Bacterial - genetics</subject><subject>Fluoroquinolones - pharmacology</subject><subject>Fluoroquinolones - therapeutic use</subject><subject>gyrA polymorphism</subject><subject>Helicobacter Infections - drug therapy</subject><subject>Helicobacter Infections - microbiology</subject><subject>Helicobacter pylori</subject><subject>Helicobacter pylori - drug effects</subject><subject>Helicobacter pylori - genetics</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular diagnosis</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic</subject><subject>QRDR</subject><subject>Quinolones</subject><issn>0924-8579</issn><issn>1872-7913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1DAUhSMEokPhFZBZwG4G_2TywwKpGgFFqsQCurYc-2bmDo4dbKdVXosnxNGM1IoNrLzwd-49OucWxRtGN4yy6v1xg0flEg6o1X7DKa02jG0orZ8UK9bUfF23TDwtVrTl5brZ1u1F8SLGI6VsK8rt8-KC1YIK0fJV8ft2NCoB8Y70dvLB_5rQeesdkAARY1JOA0FHrsGi9p3SCQIZZ-sDkg_EwT0ZpqQSeheJBWXQ7Unyj8XKGdJjiIkYiDrguMDE90SR_RyuyOjtPPgwHjAORMXoNWZHhtxjOpDDPEKIU9SQZR1aTPPL4lmvbIRX5_eyuP386cfuen3z7cvX3dXNWpctS2vBVcVM3ZuGi6Zrtx2IHjjjTWO6nIkxlaCMtiLTVIu6EaYte8WqXuXPrenEZfHuNHdcUoGY5IDZh7XKgZ-irCkv66op_wlyyttyW4oMtidQBx9jgF6OAQcVZsmoXJqVR_moWbk0KxmTudmsfX1eMnUDmAflucoMvD0DKmpl-5DDx_jANRWr847M7U4c5OzuEIKMGiEXZTCATtJ4_C87H_-aoi26jNmfMEM8-im4XI5kMnJJ5fflFJdLpBWlZZ3T_gOivOIJ</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Cattoir, Vincent</creator><creator>Nectoux, Juliette</creator><creator>Lascols, Christine</creator><creator>Deforges, Lionel</creator><creator>Delchier, Jean-Charles</creator><creator>Megraud, Francis</creator><creator>Soussy, Claude-James</creator><creator>Cambau, Emmanuelle</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20070401</creationdate><title>Update on fluoroquinolone resistance in Helicobacter pylori : new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility</title><author>Cattoir, Vincent ; Nectoux, Juliette ; Lascols, Christine ; Deforges, Lionel ; Delchier, Jean-Charles ; Megraud, Francis ; Soussy, Claude-James ; Cambau, Emmanuelle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-32a61d7fd8238b95be3fe21288db857dd6301093c490c3783d94fa16fa57d5db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Amino Acid Sequence</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Bacterial diseases</topic><topic>Bacterial diseases of the digestive system and abdomen</topic><topic>Biological and medical sciences</topic><topic>Ciprofloxacin - pharmacology</topic><topic>DNA gyrase</topic><topic>DNA Gyrase - drug effects</topic><topic>DNA Gyrase - genetics</topic><topic>Drug Resistance, Bacterial - genetics</topic><topic>Fluoroquinolones - pharmacology</topic><topic>Fluoroquinolones - therapeutic use</topic><topic>gyrA polymorphism</topic><topic>Helicobacter Infections - drug therapy</topic><topic>Helicobacter Infections - microbiology</topic><topic>Helicobacter pylori</topic><topic>Helicobacter pylori - drug effects</topic><topic>Helicobacter pylori - genetics</topic><topic>Human bacterial diseases</topic><topic>Humans</topic><topic>Infectious Disease</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular diagnosis</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic</topic><topic>QRDR</topic><topic>Quinolones</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cattoir, Vincent</creatorcontrib><creatorcontrib>Nectoux, Juliette</creatorcontrib><creatorcontrib>Lascols, Christine</creatorcontrib><creatorcontrib>Deforges, Lionel</creatorcontrib><creatorcontrib>Delchier, Jean-Charles</creatorcontrib><creatorcontrib>Megraud, Francis</creatorcontrib><creatorcontrib>Soussy, Claude-James</creatorcontrib><creatorcontrib>Cambau, Emmanuelle</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cattoir, Vincent</au><au>Nectoux, Juliette</au><au>Lascols, Christine</au><au>Deforges, Lionel</au><au>Delchier, Jean-Charles</au><au>Megraud, Francis</au><au>Soussy, Claude-James</au><au>Cambau, Emmanuelle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Update on fluoroquinolone resistance in Helicobacter pylori : new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>29</volume><issue>4</issue><spage>389</spage><epage>396</epage><pages>389-396</pages><issn>0924-8579</issn><eissn>1872-7913</eissn><abstract>Abstract Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004–2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC50 = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a ‘test and treat’ strategy that can confidently rely on QRDR gyrA sequencing.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>17303392</pmid><doi>10.1016/j.ijantimicag.2006.11.007</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0924-8579 |
| ispartof | International journal of antimicrobial agents, 2007-04, Vol.29 (4), p.389-396 |
| issn | 0924-8579 1872-7913 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70247684 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amino Acid Sequence Anti-Bacterial Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Bacterial diseases Bacterial diseases of the digestive system and abdomen Biological and medical sciences Ciprofloxacin - pharmacology DNA gyrase DNA Gyrase - drug effects DNA Gyrase - genetics Drug Resistance, Bacterial - genetics Fluoroquinolones - pharmacology Fluoroquinolones - therapeutic use gyrA polymorphism Helicobacter Infections - drug therapy Helicobacter Infections - microbiology Helicobacter pylori Helicobacter pylori - drug effects Helicobacter pylori - genetics Human bacterial diseases Humans Infectious Disease Infectious diseases Medical sciences Microbial Sensitivity Tests Molecular diagnosis Molecular Sequence Data Mutation Pharmacology. Drug treatments Polymorphism, Genetic QRDR Quinolones |
| title | Update on fluoroquinolone resistance in Helicobacter pylori : new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T22%3A28%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Update%20on%20fluoroquinolone%20resistance%20in%20Helicobacter%20pylori%20:%20new%20mutations%20leading%20to%20resistance%20and%20first%20description%20of%20a%20gyrA%20polymorphism%20associated%20with%20hypersusceptibility&rft.jtitle=International%20journal%20of%20antimicrobial%20agents&rft.au=Cattoir,%20Vincent&rft.date=2007-04-01&rft.volume=29&rft.issue=4&rft.spage=389&rft.epage=396&rft.pages=389-396&rft.issn=0924-8579&rft.eissn=1872-7913&rft_id=info:doi/10.1016/j.ijantimicag.2006.11.007&rft_dat=%3Cproquest_cross%3E20294543%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20294543&rft_id=info:pmid/17303392&rft_els_id=S0924857906004778&rfr_iscdi=true |