{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:21:44Z","timestamp":1790014904814,"version":"4.0.1"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"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":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Experimental and clinical studies have indicated that the antileprosy drug clofazimine may contribute treatment-shortening activity when included in tuberculosis treatment regimens. Clofazimine accumulates to high levels in tissues, has a long half-life, and remains in the body for months after administration is stopped. We hypothesized that in tuberculosis treatment, accumulated clofazimine may contribute sustained antimicrobial activity after treatment cessation, and we used the BALB\/c mouse model of chronic tuberculosis chemotherapy to address this hypothesis.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            -infected mice were treated for 4 weeks or 8 weeks with either isoniazid alone, clofazimine alone, the first-line regimen rifampin-isoniazid-pyrazinamide-ethambutol, or a first-line regimen where clofazimine was administered in place of ethambutol. To evaluate posttreatment antimicrobial activity, bacterial regrowth in the lungs and spleens was assessed at the day of treatment cessation and 2, 4, 6, and 8 weeks after treatment was stopped. Bacterial regrowth was delayed in all mice receiving clofazimine, either alone or in combination, compared to the mice that did not receive clofazimine. This effect was especially evident in mice receiving multidrug therapy. In mice not receiving clofazimine, bacterial regrowth began almost immediately after treatment was stopped, while in mice receiving clofazimine, bacterial regrowth was delayed for up to 6 weeks, with the duration of sustained antimicrobial activity being positively associated with the time that serum clofazimine levels remained at or above the 0.25-\u03bcg\/ml MIC for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            . Thus, sustained activity of clofazimine may be important in the treatment-shortening effect associated with this drug.\n          <\/jats:p>","DOI":"10.1128\/aac.00177-16","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T04:04:31Z","timestamp":1456805071000},"page":"2864-2869","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Clofazimine Contributes Sustained Antimicrobial Activity after Treatment Cessation in a Mouse Model of Tuberculosis Chemotherapy"],"prefix":"10.1128","volume":"60","author":[{"given":"Rosemary V.","family":"Swanson","sequence":"first","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"},{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C.","family":"Ammerman","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"},{"name":"Center for Tuberculosis Research, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bongani","family":"Ngcobo","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Adamson","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chivonne","family":"Moodley","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afton","family":"Dorasamy","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sashen","family":"Moodley","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinhle","family":"Mgaga","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda A.","family":"Bester","sequence":"additional","affiliation":[{"name":"Biomedical Resources Unit, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanil D.","family":"Singh","sequence":"additional","affiliation":[{"name":"Biomedical Resources Unit, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak V.","family":"Almeida","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"},{"name":"Center for Tuberculosis Research, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques H.","family":"Grosset","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa"},{"name":"Center for Tuberculosis Research, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1956.tb12238.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/1791013a0"},{"key":"e_1_3_3_4_2","volume-title":"WHO\/CDS\/CPE\/CEE\/2004.46","author":"World Health Organization","year":"2004","unstructured":"World Health Organization. 2004. Multidrug therapy against leprosy: development and implementation over the past 25 years. WHO\/CDS\/CPE\/CEE\/2004.46. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis460"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0077OC"},{"key":"e_1_3_3_7_2","volume-title":"2013 update","author":"World Health Organization","year":"2013","unstructured":"World Health Organization. 2013. Multidrug-resistant tuberculosis (MDR-TB). 2013 update. 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