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Gepotidacin selectively inhibits type II topoisomerases involved in bacterial DNA replication by a distinct binding site and novel mechanism of action, conferring\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity against most uropathogens, including those resistant to current antimicrobials. This study evaluated the potential of gepotidacin to select for spontaneous resistance in\n                      <jats:italic toggle=\"yes\">Citrobacter freundii<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                      species complex,\n                      <jats:italic toggle=\"yes\">Klebsiella aerogenes<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Proteus mirabilis<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Providencia rettgeri<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Staphylococcus saprophyticus<\/jats:italic>\n                      clinical isolates. Mutant frequencies ranged from 6.1 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      to &lt;2.5 \u00d7 10\n                      <jats:sup>\u221210<\/jats:sup>\n                      at 4\u00d7 gepotidacin MIC concentrations, and no mutant isolates were recovered at 10\u00d7 gepotidacin MIC concentrations. No target gene-specific (\n                      <jats:italic toggle=\"yes\">gyrA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">gyrB<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">parC<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">parE<\/jats:italic>\n                      ) cross-resistance was observed with any of the comparators tested. As gepotidacin target site mutations in\n                      <jats:italic toggle=\"yes\">gyrA\/B<\/jats:italic>\n                      were only found in\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                      , repressor inactivation or activator dysregulation mutations in efflux pumps were identified as possible mechanisms of reduced susceptibility in the Gram-negative isolates. Further investigation is needed into the relevance of these resistance mechanisms, the clinical significance of these findings, and whether there are any potential fitness costs of decreased gepotidacin susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01832-25","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:53:42Z","timestamp":1777557222000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Determination of frequency of spontaneous resistance for gepotidacin and levofloxacin against a collection of gram-positive and gram-negative organisms"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-1657","authenticated-orcid":true,"given":"Gina M.","family":"Morgan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-1543","authenticated-orcid":true,"given":"John H.","family":"Kimbrough","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura H.","family":"Karr","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Thompson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"West","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-6238","authenticated-orcid":true,"given":"S. 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