{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:46:23Z","timestamp":1772689583641,"version":"3.50.1"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1995,2,1]],"date-time":"1995-02-01T00:00:00Z","timestamp":791596800000},"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":[[1995,2]]},"abstract":"<jats:p>We investigated the activity of benzoxazinorifamycin (KRM-1648) against several drug-susceptible and multidrug-resistant strains of tubercle bacilli. Since KRM-1648 is a rifamycin derivative, we included some strains of Mycobacterium tuberculosis resistant to rifampin (RIF) among the multidrug-resistant strains. For RIF-susceptible strains, the MIC of KRM-1648 was much lower than that of RIF (MICs of KRM-1648 and RIF at which 90% of strains are inhibited, &lt; or = 0.015 and &lt; or = 0.25 micrograms\/ml, respectively). The MBC of KRM-1648 (range, 0.007 to 0.03 microgram\/ml) was also much lower than that of RIF (range, 0.5 to 1.0 microgram\/ml). Postantibiotic effect studies with KRM-1648 showed a rapid reduction in the CFU counts with an exposure of 24 h or more, and its sterilizing effect was maintained even up to 21 days thereafter. Parallel postantibiotic effect studies with RIF showed a less significant effect with a faster recovery of growth, and RIF failed to sterilize the organisms even after 72 h of exposure. KRM-1648 at 0.125 and 0.25 microgram\/ml caused complete inhibition of intracellular growth of M. tuberculosis in J774 A.1 macrophages after 48 h of exposure. After a similar exposure time RIF at a concentration of 0.25 microgram\/ml caused complete inhibition of growth, but a concentration of 0.125 microgram\/ml caused only a 50% reduction in growth compared with that of controls at day 7. With 24 h of pulsed exposure of the intracellular organisms to 0.25 micrograms of the drugs per ml, KRM-1648 caused complete inhibition of intracellular growth, while RIF caused only moderate inhibition of intracellular growth. These findings suggest that KRM-1648 is a potentially useful drug for the treatment of tuberculosis.<\/jats:p>","DOI":"10.1128\/aac.39.2.440","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:06:25Z","timestamp":1340841985000},"page":"440-444","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli"],"prefix":"10.1128","volume":"39","author":[{"given":"J","family":"Luna-Herrera","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago 60612, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M V","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago 60612, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P R","family":"Gangadharam","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago 60612, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.2.440","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.2.440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:06:56Z","timestamp":1645474016000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.39.2.440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,2]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,2]]}},"alternative-id":["10.1128\/AAC.39.2.440"],"URL":"https:\/\/doi.org\/10.1128\/aac.39.2.440","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,2]]},"assertion":[{"value":"1995-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}