{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:04Z","timestamp":1791414124603,"version":"4.3.3"},"reference-count":37,"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><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Clostridium difficile<\/jats:named-content>is a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report the<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>antibacterial evaluation of cadazolid against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>. Cadazolid showed potent<jats:italic>in vitro<\/jats:italic>activity against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>with a MIC range of 0.125 to 0.5 \u03bcg\/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>isolates, with &gt;99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibited<jats:italic>de novo<\/jats:italic>toxin A and B formation in stationary-phase cultures of toxigenic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>. Cadazolid also inhibited<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>spore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD.<\/jats:p>","DOI":"10.1128\/aac.01830-13","type":"journal-article","created":{"date-parts":[[2013,11,26]],"date-time":"2013-11-26T03:28:07Z","timestamp":1385436487000},"page":"892-900","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["<i>In Vitro<\/i>and<i>In Vivo<\/i>Antibacterial Evaluation 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":"Peter","family":"Seiler","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"}],"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":"Michel","family":"Enderlin","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Klenk","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvire","family":"Fournier","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hubschwerlen","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"}]},{"given":"Ciaran P.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Keck","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.190"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2164"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.02.073"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051590"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/655998"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0707500"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/667733"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.2.4.16109"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2011.07.017"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir643"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.31.9.877"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70374-7"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0910812"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis462"},{"key":"e_1_3_3_16_2","volume-title":"Abstr. 52nd Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA. American Society for Microbiology","author":"Hecht DW","year":"2012","unstructured":"HechtDWOsmolskiJRSambolSCheknisAGerdingDN. 2012. In vitro activity of cadazolid against 209 toxigenic isolates of Clostridium difficile, abstr E-808. Abstr. 52nd Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2013.02.003"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt411"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt401"},{"key":"e_1_3_3_20_2","volume-title":"Abstr. 53rd Eur. Cong. Clin. Microbiol. Infect. Dis.","author":"Louie TJ","year":"2013","unstructured":"LouieTJBuitragoMCornelyOAKrackerHRangarajuMCharefP. 2013. Multicentre, double-blind, randomised, phase 2 study evaluating the novel antibiotic, cadazolid, in subjects with Clostridium difficile-associated diarrhea, abstract\/poster LB-2956. Abstr. 53rd Eur. Cong. Clin. Microbiol. Infect. Dis., Berlin, Germany."},{"key":"e_1_3_3_21_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. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp042"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.47739-0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr033"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis453"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.09.002"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","article-title":"Regression models and life tables (with discussion)","volume":"34","author":"Cox DR","year":"1972","unstructured":"CoxDR. 1972. Regression models and life tables (with discussion). J. R. Statist. Soc. B 34:187\u2013220.","journal-title":"J. R. Statist. Soc. B"},{"key":"e_1_3_3_28_2","volume-title":"Abstr. 52nd Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA. American Society for Microbiology","author":"Locher HH","year":"2012","unstructured":"LocherHHPfaffPSchroederSSpecklinJLHubschwerlenCKeckW. 2012. Cadazolid, a novel quinolonyl-oxazolidinone antibiotic with potent activity against Clostridium difficile: in vitro antibacterial activity and propensity for resistance development, abstr C1-1346. Abstr. 52nd Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01443-07"},{"key":"e_1_3_3_30_2","first-page":"77","article-title":"Fidaxomicin inhibits production of toxin A and toxin B in Clostridium difficile","volume":"7","author":"Bouillaut L","year":"2012","unstructured":"BouillautLSimsCGomezASearsPSeddonJSonensheinA. 2012. Fidaxomicin inhibits production of toxin A and toxin B in Clostridium difficile. J. Hosp. Med. 7(Suppl 2):77. http:\/\/www.shmabstracts.com\/abstract.asp?MeetingID=783&id=97620.","journal-title":"J. Hosp. Med."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01831-13"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01143-07"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/136.5.701"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1086\/345676"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00877-12"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.6.1108"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00057-12"},{"key":"e_1_3_3_38_2","volume-title":"Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL, abstr K-205a. American Society for Microbiology","author":"Patino H","year":"2011","unstructured":"PatinoHStevensCLouieTJBernardoPFriedlandI. 2011. Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL, abstr K-205a. American Society for Microbiology, Washington, DC."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01830-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01830-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T10:58:48Z","timestamp":1716202728000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01830-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1128\/AAC.01830-13"],"URL":"https:\/\/doi.org\/10.1128\/aac.01830-13","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2]]},"assertion":[{"value":"2013-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}