{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:01:44Z","timestamp":1791414104423,"version":"4.3.3"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"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":[[2014,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cadazolid is a new oxazolidinone-type antibiotic currently in clinical development for the treatment of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Clostridium difficile<\/jats:named-content>\n            -associated diarrhea. Here, we report investigations on the mode of action and the propensity for spontaneous resistance development in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            strains. Macromolecular labeling experiments indicated that cadazolid acts as a potent inhibitor of protein synthesis, while inhibition of DNA synthesis was also observed, albeit only at substantially higher concentrations of the drug. Strong inhibition of protein synthesis was also obtained in strains resistant to linezolid, in agreement with low MICs against such strains. Inhibition of protein synthesis was confirmed in coupled transcription\/translation assays using extracts from different\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            strains, including strains resistant to linezolid, while inhibitory effects in DNA topoisomerase assays were weak or not detectable under the assay conditions. Spontaneous resistance frequencies of cadazolid were low in all strains tested (generally &lt;10\n            <jats:sup>\u221210<\/jats:sup>\n            at 2\u00d7 to 4\u00d7 the MIC), and in multiple-passage experiments (up to 13 passages) MICs did not significantly increase. Furthermore, no cross-resistance was observed, as cadazolid retained potent activity against strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new antibiotic fidaxomicin. In conclusion, the data presented here indicate that cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition of DNA synthesis as a potential second mode of action, and suggest a low potential for spontaneous resistance development.\n          <\/jats:p>","DOI":"10.1128\/aac.01831-13","type":"journal-article","created":{"date-parts":[[2013,11,26]],"date-time":"2013-11-26T03:28:07Z","timestamp":1385436487000},"page":"901-908","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":73,"title":["Investigations of the Mode of Action and Resistance Development of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections"],"prefix":"10.1128","volume":"58","author":[{"given":"Hans H.","family":"Locher","sequence":"first","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Caspers","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Bruy\u00e8re","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pfaff","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreja","family":"Knezevic","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Keck","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ritz","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd., Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2164"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhm.1916"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-007-6113-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.215"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.190"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2010.495386"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.31.9.877"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0910812"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70374-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2013.02.003"},{"key":"e_1_3_2_12_2","volume-title":"Abstr. 52nd Intersci. 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Cadazolid, a novel quinolonyl-oxazolidinone antibiotic: mode of action and effect on Clostridium difficile toxin and spore formation, abstr C1-1347. Abstr. 52nd Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.07.030"},{"key":"e_1_3_2_18_2","volume-title":"Methods for antimicrobial susceptibility testing of anaerobic bacteria: approved standard\u20147th ed, M11-A7","author":"CLSI","year":"2007","unstructured":"CLSI. 2007. Methods for antimicrobial susceptibility testing of anaerobic bacteria: approved standard\u20147th ed, M11-A7. 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In vitro activity of cadazolid (ACT-179811) against Clostridium difficile and in an in vitro gut model of C. difficile infection, abstr B-662. Abstr. 52nd Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA. 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