{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:11:16Z","timestamp":1791277876340,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            AAC(6\u2032)-Ib-cr is a plasmid-mediated quinolone resistance mechanism described worldwide for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            . Since it confers\n            <jats:italic>in vitro<\/jats:italic>\n            only a low level of resistance to ciprofloxacin, we evaluated its impact on the\n            <jats:italic>in vivo<\/jats:italic>\n            activity of ciprofloxacin. Isogenic strains were obtained by transferring plasmid p449, harboring\n            <jats:italic>aac(6<\/jats:italic>\n            \u2032\n            <jats:italic>)-Ib-cr<\/jats:italic>\n            , into the quinolone-susceptible strain\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            CFT073-RR and its D87G\n            <jats:italic>gyrA<\/jats:italic>\n            mutant. MICs were 0.015, 0.06, 0.25, and 0.5 \u03bcg\/ml against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            strains CFT073-RR, CFT073-RR\/p449, CFT073-RR GyrA\n            <jats:sup>r<\/jats:sup>\n            , and CFT073-RR GyrA\n            <jats:sup>r<\/jats:sup>\n            \/p449, respectively. Bactericidal activity was reduced at 1\u00d7 the MIC for the three resistant derivatives, while at a fixed concentration of 0.5 \u03bcg\/ml, 99.9% killing was observed for all strains except\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            CFT073-RR GyrA\n            <jats:sup>r<\/jats:sup>\n            \/p449. In the murine model of pyelonephritis, an optimal regimen of ciprofloxacin (10 mg\/kg of body weight twice a day [b.i.d.]) significantly decreased the bacterial count in the kidneys of mice infected with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            CFT073 (1.6 versus 4.3 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g of kidney compared to untreated controls;\n            <jats:italic>P<\/jats:italic>\n            = 0.0001), while no significant decrease was observed for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            CFT073-RR\/p449 (2.7 versus 3.1 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g;\n            <jats:italic>P<\/jats:italic>\n            = 0.84),\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            CFT073-RR GyrA\n            <jats:sup>r<\/jats:sup>\n            (4.2 versus 4.1 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g;\n            <jats:italic>P<\/jats:italic>\n            = 0.35), or\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            CFT073-RR GyrA\n            <jats:sup>r<\/jats:sup>\n            \/p449 (2.9 versus 3.6 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g;\n            <jats:italic>P<\/jats:italic>\n            = 0.47). While pharmacokinetic and pharmacodynamic (PK\/PD) parameters accounted for ciprofloxacin failure against\n            <jats:italic>gyrA<\/jats:italic>\n            -containing mutants, this was not the case for the\n            <jats:italic>aac(6<\/jats:italic>\n            \u2032\n            <jats:italic>)-Ib-cr<\/jats:italic>\n            -containing strains, suggesting an\n            <jats:italic>in situ<\/jats:italic>\n            hydrolysis of ciprofloxacin in the latter case.\n          <\/jats:p>","DOI":"10.1128\/aac.01489-13","type":"journal-article","created":{"date-parts":[[2013,9,10]],"date-time":"2013-09-10T01:54:39Z","timestamp":1378778079000},"page":"5830-5835","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Ciprofloxacin Treatment Failure in a Murine Model of Pyelonephritis Due to an AAC(6\u2032)-Ib-cr-Producing Escherichia coli Strain Susceptible to Ciprofloxacin\n            <i>In Vitro<\/i>"],"prefix":"10.1128","volume":"57","author":[{"given":"T.","family":"Guillard","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA4687 SFR CAP-Sant\u00e9, Reims, France"},{"name":"PRES Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Diderot-Paris 7, EA3964, Paris, France"},{"name":"CHU Reims, H\u00f4pital Robert Debr\u00e9, Laboratoire de Bact\u00e9riologie-Virologie-Hygi\u00e8ne, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Cambau","sequence":"additional","affiliation":[{"name":"PRES Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Diderot-Paris 7, EA3964, Paris, France"},{"name":"AP-HP, Groupe Hospitalier Lariboisi\u00e8re-Saint Louis, Laboratoire de Bact\u00e9riologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Chau","sequence":"additional","affiliation":[{"name":"PRES Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Diderot-Paris 7, EA3964, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Massias","sequence":"additional","affiliation":[{"name":"AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Laboratoire de Pharmacologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"de Champs","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Reims Champagne-Ardenne, EA4687 SFR CAP-Sant\u00e9, Reims, France"},{"name":"CHU Reims, H\u00f4pital Robert Debr\u00e9, Laboratoire de Bact\u00e9riologie-Virologie-Hygi\u00e8ne, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Fantin","sequence":"additional","affiliation":[{"name":"PRES Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Diderot-Paris 7, EA3964, Paris, France"},{"name":"AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Service de m\u00e9decine interne, Clichy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/314056"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02725.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2736"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01617-06"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00016-09"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)07322-4"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00143-07"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.2.798-799.2003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1347"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00886-08"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0691.2000.00142.x"},{"key":"e_1_3_2_13_2","volume-title":"Performance standards for antimicrobial susceptibility testing: twenty-first informational supplement M100-S21","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. 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