<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-00517531</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-19T02:28:13+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Influence of inoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of Klebsiella pneumoniae in a rat lung infection model.</title>
            <author role="aut">
              <persName>
                <forename type="first">Anne-Sylvie</forename>
                <surname>Kesteman</surname>
              </persName>
              <idno type="halauthorid">491166-0</idno>
              <affiliation ref="#struct-93481"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Aude A</forename>
                <surname>Ferran</surname>
              </persName>
              <email type="md5">325e645481a9671a6aa2eb8a5785201d</email>
              <email type="domain">envt.fr</email>
              <idno type="idhal" notation="string">audeferran</idno>
              <idno type="idhal" notation="numeric">744273</idno>
              <idno type="halauthorid" notation="string">491170-744273</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/J-6344-2013</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-6629-1088</idno>
              <idno type="GOOGLE SCHOLAR">https://scholar.google.com/citations?user=6fTSiHoAAAAJ&amp;hl=fr</idno>
              <idno type="IDREF">https://www.idref.fr/119658151</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/J-6344-2013</idno>
              <affiliation ref="#struct-93481"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Agnès</forename>
                <surname>Perrin-Guyomard</surname>
              </persName>
              <email type="md5">638c4b3812a1dd6d5ca196282cd3381e</email>
              <email type="domain">anses.fr</email>
              <idno type="idhal" notation="string">agnes-perrin</idno>
              <idno type="idhal" notation="numeric">747394</idno>
              <idno type="halauthorid" notation="string">406615-747394</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-4078-188X</idno>
              <affiliation ref="#struct-69545"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Michel</forename>
                <surname>Laurentie</surname>
              </persName>
              <idno type="halauthorid">406643-0</idno>
              <affiliation ref="#struct-69545"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Pascal</forename>
                <surname>Sanders</surname>
              </persName>
              <email type="md5">617dc73d0162cdc4788651e5b73944ed</email>
              <email type="domain">anses.fr</email>
              <idno type="idhal" notation="string">pascal-sanders</idno>
              <idno type="idhal" notation="numeric">15081</idno>
              <idno type="halauthorid" notation="string">11297-15081</idno>
              <idno type="IDREF">https://www.idref.fr/06862977X</idno>
              <idno type="ORCID">https://orcid.org/0000-0003-4019-480X</idno>
              <affiliation ref="#struct-69545"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Pierre-Louis</forename>
                <surname>Toutain</surname>
              </persName>
              <idno type="idhal" notation="numeric">761603</idno>
              <idno type="halauthorid" notation="string">410613-761603</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-8846-8892</idno>
              <affiliation ref="#struct-93481"/>
            </author>
            <author role="crp">
              <persName>
                <forename type="first">Alain</forename>
                <surname>Bousquet‐mélou</surname>
              </persName>
              <email type="md5">60427ef5078f0af4c61d811bbb2f457f</email>
              <email type="domain">inrae.fr</email>
              <idno type="idhal" notation="string">alain-bousquet-melou</idno>
              <idno type="idhal" notation="numeric">1480601</idno>
              <idno type="halauthorid" notation="string">2154018-1480601</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-7661-4311</idno>
              <idno type="IDREF">https://www.idref.fr/059552964</idno>
              <idno type="GOOGLE SCHOLAR">https://scholar.google.fr/citations?user=oPu1VDwAAAAJ</idno>
              <affiliation ref="#struct-93481"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Alain</forename>
                <surname>Bousquet-Mélou</surname>
              </persName>
              <email type="md5">47fcb0ae6ca1377dd686e1c0ab50fbd1</email>
              <email type="domain">envt.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2010-09-16 11:40:55</date>
              <date type="whenModified">2026-03-18 14:22:02</date>
              <date type="whenReleased">2010-09-16 13:15:20</date>
              <date type="whenProduced">2009-11</date>
              <date type="whenEndEmbargoed">2010-09-16</date>
              <ref type="file" target="https://hal.science/hal-00517531v1/document">
                <date notBefore="2010-09-16"/>
              </ref>
              <ref type="file" subtype="author" n="1" target="https://hal.science/hal-00517531v1/file/Kesteman_Authors_Manuscript_AAC_2009.pdf" id="file-517531-272021">
                <date notBefore="2010-09-16"/>
              </ref>
              <ref type="externalLink" target="https://aac.asm.org/content/53/11/4740.full.pdf"/>
              <fs>
                <f name="inra_publicVise_local" notation="string" n="SC">
                  <string>inra_publicVise_local_SC</string>
                </f>
              </fs>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="154367">
                <persName>
                  <forename>Alain</forename>
                  <surname>Bousquet-Mélou</surname>
                </persName>
                <email type="md5">47fcb0ae6ca1377dd686e1c0ab50fbd1</email>
                <email type="domain">envt.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-00517531</idno>
            <idno type="halUri">https://hal.science/hal-00517531</idno>
            <idno type="halBibtex">kesteman:hal-00517531</idno>
            <idno type="halRefHtml">&lt;i&gt;Antimicrobial Agents and Chemotherapy&lt;/i&gt;, 2009, 53 (11), pp.4740-8. &lt;a target="_blank" href="https://dx.doi.org/10.1128/AAC.00608-09"&gt;&amp;#x27E8;10.1128/AAC.00608-09&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Antimicrobial Agents and Chemotherapy, 2009, 53 (11), pp.4740-8. &amp;#x27E8;10.1128/AAC.00608-09&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://about.hal.science/hal-authorisation-v1/">HAL Authorization<ref corresp="#file-517531-272021"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="ANSES">Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail</idno>
            <idno type="stamp" n="INRA">INRA - Institut national de la recherche agronomique</idno>
            <idno type="stamp" n="AGREENIUM">Archive ouverte en agrobiosciences</idno>
            <idno type="stamp" n="INRAE">Institut National de Recherche en Agriculture, Alimentation et Environnement</idno>
            <idno type="stamp" n="TOULOUSE-INP">Toulouse - INP</idno>
            <idno type="stamp" n="UT3-INP">Université de Toulouse / Toulouse INP</idno>
            <idno type="stamp" n="UT3-TOULOUSEINP">Université de Toulouse / Toulouse INP</idno>
            <idno type="stamp" n="ENVT">École Nationale Vétérinaire de Toulouse </idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">Influence of inoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of Klebsiella pneumoniae in a rat lung infection model.</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Anne-Sylvie</forename>
                    <surname>Kesteman</surname>
                  </persName>
                  <idno type="halauthorid">491166-0</idno>
                  <affiliation ref="#struct-93481"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Aude A</forename>
                    <surname>Ferran</surname>
                  </persName>
                  <email type="md5">325e645481a9671a6aa2eb8a5785201d</email>
                  <email type="domain">envt.fr</email>
                  <idno type="idhal" notation="string">audeferran</idno>
                  <idno type="idhal" notation="numeric">744273</idno>
                  <idno type="halauthorid" notation="string">491170-744273</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/J-6344-2013</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-6629-1088</idno>
                  <idno type="GOOGLE SCHOLAR">https://scholar.google.com/citations?user=6fTSiHoAAAAJ&amp;hl=fr</idno>
                  <idno type="IDREF">https://www.idref.fr/119658151</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/J-6344-2013</idno>
                  <affiliation ref="#struct-93481"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Agnès</forename>
                    <surname>Perrin-Guyomard</surname>
                  </persName>
                  <email type="md5">638c4b3812a1dd6d5ca196282cd3381e</email>
                  <email type="domain">anses.fr</email>
                  <idno type="idhal" notation="string">agnes-perrin</idno>
                  <idno type="idhal" notation="numeric">747394</idno>
                  <idno type="halauthorid" notation="string">406615-747394</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-4078-188X</idno>
                  <affiliation ref="#struct-69545"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Michel</forename>
                    <surname>Laurentie</surname>
                  </persName>
                  <idno type="halauthorid">406643-0</idno>
                  <affiliation ref="#struct-69545"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Pascal</forename>
                    <surname>Sanders</surname>
                  </persName>
                  <email type="md5">617dc73d0162cdc4788651e5b73944ed</email>
                  <email type="domain">anses.fr</email>
                  <idno type="idhal" notation="string">pascal-sanders</idno>
                  <idno type="idhal" notation="numeric">15081</idno>
                  <idno type="halauthorid" notation="string">11297-15081</idno>
                  <idno type="IDREF">https://www.idref.fr/06862977X</idno>
                  <idno type="ORCID">https://orcid.org/0000-0003-4019-480X</idno>
                  <affiliation ref="#struct-69545"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Pierre-Louis</forename>
                    <surname>Toutain</surname>
                  </persName>
                  <idno type="idhal" notation="numeric">761603</idno>
                  <idno type="halauthorid" notation="string">410613-761603</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-8846-8892</idno>
                  <affiliation ref="#struct-93481"/>
                </author>
                <author role="crp">
                  <persName>
                    <forename type="first">Alain</forename>
                    <surname>Bousquet‐mélou</surname>
                  </persName>
                  <email type="md5">60427ef5078f0af4c61d811bbb2f457f</email>
                  <email type="domain">inrae.fr</email>
                  <idno type="idhal" notation="string">alain-bousquet-melou</idno>
                  <idno type="idhal" notation="numeric">1480601</idno>
                  <idno type="halauthorid" notation="string">2154018-1480601</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-7661-4311</idno>
                  <idno type="IDREF">https://www.idref.fr/059552964</idno>
                  <idno type="GOOGLE SCHOLAR">https://scholar.google.fr/citations?user=oPu1VDwAAAAJ</idno>
                  <affiliation ref="#struct-93481"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">10566</idno>
                <idno type="issn">0066-4804</idno>
                <idno type="eissn">1098-6596</idno>
                <title level="j">Antimicrobial Agents and Chemotherapy</title>
                <imprint>
                  <publisher>American Society for Microbiology</publisher>
                  <biblScope unit="volume">53</biblScope>
                  <biblScope unit="issue">11</biblScope>
                  <biblScope unit="pp">4740-8</biblScope>
                  <date type="datePub">2009-11</date>
                  <date type="dateEpub">2009-09-08</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1128/AAC.00608-09</idno>
              <idno type="prodinra">34696</idno>
              <idno type="pubmed">19738020</idno>
              <idno type="wos">000270881200022</idno>
              <ref target="http://gateway.isiknowledge.com/gateway/Gateway.cgi?&amp;GWVersion=2&amp;SrcAuth=INRA&amp;SrcApp=INRA&amp;DestLinkType=FullRecord&amp;DestApp=WOS&amp;KeyUT=000270881200022" type="seeAlso"/>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">marbofloxacine</term>
                <term xml:lang="en">agent pathogène</term>
                <term xml:lang="en">enterobacteriaceae</term>
                <term xml:lang="fr">modèle</term>
                <term xml:lang="fr">infection</term>
                <term xml:lang="fr">bactérie</term>
                <term xml:lang="fr">résistance</term>
                <term xml:lang="fr">microorganisme</term>
                <term xml:lang="fr">klebsiella pneumoniae</term>
                <term xml:lang="fr">pneumonie</term>
                <term xml:lang="fr">poumon</term>
                <term xml:lang="fr">infection respiratoire</term>
              </keywords>
              <classCode scheme="mesh">Animals</classCode>
              <classCode scheme="mesh">Anti-Infective Agents</classCode>
              <classCode scheme="mesh">Microbial Sensitivity Tests</classCode>
              <classCode scheme="mesh">Rats</classCode>
              <classCode scheme="mesh">Area Under Curve</classCode>
              <classCode scheme="mesh">Dose-Response Relationship, Drug</classCode>
              <classCode scheme="mesh">Drug Resistance, Bacterial</classCode>
              <classCode scheme="mesh">Fluoroquinolones</classCode>
              <classCode scheme="mesh">Klebsiella Infections</classCode>
              <classCode scheme="mesh">Klebsiella pneumoniae</classCode>
              <classCode scheme="mesh">Lung</classCode>
              <classCode scheme="mesh">Male</classCode>
              <classCode scheme="halDomain" n="sdv.sp.pharma">Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after infection with a low (10(5) CFU) or a high (10(9) CFU) inoculum of Klebsiella pneumoniae. For daily fractionated doses of marbofloxacin, prevention of resistance occurred for an area-under-the-concentration-time-curve (AUC)/MIC ratio of 189 h for the low inoculum, whereas for the high inoculum, resistant-subpopulation enrichment occurred for AUC/MIC ratios up to 756 h. For the high-inoculum-infected rats, the AUC/MIC ratio, C(max)/MIC ratio, and time within the mutant selection window (T(MSW)) were not found to be effective predictors of resistance prevention upon comparison of fractionated and single administrations. An index corresponding to the ratio of the time that the drug concentrations were above the mutant prevention concentration (MPC) over the time that the drug concentrations were within the MSW (T(&gt;MPC)/T(MSW)) was the best predictor of the emergence of resistance: a T(&gt;MPC)/T(MSW) ratio of 0.54 was associated with prevention of resistance for both fractionated and single administrations. These results suggest that the enrichment of resistant bacteria depends heavily on the inoculum size at the start of an antimicrobial treatment and that classical PK/PD parameters cannot adequately describe the impact of different dosage regimens on enrichment of resistant bacteria. We propose an original index, the T(&gt;MPC)/T(MSW) ratio, which reflects the ratio of the time that the less susceptible bacterial subpopulation is killed over the time that it is selected, as a potentially powerful indicator of prevention of enrichment of resistant bacteria. This ratio is valid only if plasma concentrations achieve the MPC.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-93481" status="OLD">
          <orgName>Physiologie et Toxicologie Expérimentales</orgName>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
          </desc>
          <listRelation>
            <relation name="UMR181" active="#struct-92114" type="direct"/>
            <relation active="#struct-300421" type="direct"/>
            <relation active="#struct-448187" type="indirect"/>
            <relation active="#struct-443875" type="indirect"/>
          </listRelation>
        </org>
        <org type="laboratory" xml:id="struct-69545" status="OLD">
          <orgName>Laboratoire d'études et de recherches sur les médicaments vétérinaires et les désinfectants</orgName>
          <desc>
            <address>
              <addrLine>La Haute Marche Javené BP 90203 35302 FOUGÈRES Cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.afssa.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-24348" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-92114" status="OLD">
          <idno type="ROR">https://ror.org/01x3gbx83</idno>
          <orgName>Institut National de la Recherche Agronomique</orgName>
          <orgName type="acronym">INRA</orgName>
          <date type="start">1946-05-18</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inra.fr</ref>
          </desc>
        </org>
        <org type="regrouplaboratory" xml:id="struct-300421" status="VALID">
          <idno type="ROR">https://ror.org/03m3gzv89</idno>
          <orgName>École nationale vétérinaire de Toulouse</orgName>
          <orgName type="acronym">ENVT</orgName>
          <desc>
            <address>
              <addrLine>23 chemin des Capelles - 31076 Toulouse Cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://envt.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-448187" type="direct"/>
            <relation active="#struct-443875" type="indirect"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-448187" status="VALID">
          <idno type="IdRef">026388820</idno>
          <idno type="ISNI">0000000121766169</idno>
          <idno type="ROR">https://ror.org/033p9g875</idno>
          <orgName>Institut National Polytechnique (Toulouse)</orgName>
          <orgName type="acronym">Toulouse INP</orgName>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.inp-toulouse.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-443875" type="direct"/>
          </listRelation>
        </org>
        <org type="regroupinstitution" xml:id="struct-443875" status="VALID">
          <idno type="ROR">https://ror.org/017tgbk05</idno>
          <orgName>Communauté d'universités et établissements de Toulouse</orgName>
          <orgName type="acronym">Comue de Toulouse</orgName>
          <desc>
            <address>
              <addrLine>41 Allée Jules Guesde, 31000 Toulouse</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.univ-toulouse.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-24348" status="OLD">
          <orgName>Agence Française de Sécurité Sanitaire des Aliments</orgName>
          <orgName type="acronym">AFSSA</orgName>
          <date type="start">1998-01-01</date>
          <date type="end">2009-04-01</date>
          <desc>
            <address>
              <addrLine>27-31 av du Général Leclerc 94701 MAISONS-ALFORT Cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.afssa.fr/</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>