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This study examined<jats:italic>in vitro<\/jats:italic>its activity against intracellular<jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>(involved in the persistent character of skin and skin structure infections) by use of a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (the apparent bacteriostatic concentration [<jats:italic>C<jats:sub>s<\/jats:sub><\/jats:italic>] was reached at an extracellular concentration about 0.7\u00d7 its MIC and was not affected by mechanisms of resistance to the comparators) and (ii) caused a maximal reduction of the intracellular burden (maximum effect) of about \u22121.6 log<jats:sub>10<\/jats:sub>CFU (which was better than that caused by linezolid, macrolides, and daptomycin and similar to that caused by moxifloxacin). After 24 h of incubation of infected cells with antibiotics at 100\u00d7 their MIC, the intracellular persisting fraction was &lt;0.1% with moxifloxacin, 0.5% with gepotidacin, and &gt;1% with the other drugs. The accumulation and efflux of gepotidacin in phagocytes were very fast (<jats:italic>k<\/jats:italic><jats:sub>in<\/jats:sub>and<jats:italic>k<\/jats:italic><jats:sub>out<\/jats:sub>, \u223c0.3 min<jats:sup>\u22121<\/jats:sup>; the plateau was reached within 15 min) but modest (intracellular concentration-to-extracellular concentration ratio, \u223c1.6). In cell fractionation studies, about 40 to 60% of the drug was recovered in the soluble fraction and \u223c40% was associated with lysosomes in uninfected cells. In infected cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable fraction that also contained bacteria. This study highlights the potential for further study of gepotidacin to fight infections where intracellular niches may play a determining role in bacterial persistence and relapses.<\/jats:p>","DOI":"10.1128\/aac.02245-17","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T11:30:31Z","timestamp":1516620631000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of Cultured Phagocytic Cells"],"prefix":"10.1128","volume":"62","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Peyrusson","sequence":"first","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-3623","authenticated-orcid":false,"given":"Paul M.","family":"Tulkens","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-7991","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Van Bambeke","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"WHO publishes list of bacteria for which new antibiotics are urgently needed","author":"World Health Organization","unstructured":"World Health Organization. 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