{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:46:44Z","timestamp":1787921204003,"version":"build-2784847793"},"reference-count":0,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[1997,10,1]],"date-time":"1997-10-01T00:00:00Z","timestamp":875664000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[1997,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    KRM\u20131648 is a new benzoxazinorifamycin with activity\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    against organisms of the\n                    <jats:italic toggle=\"yes\">Mycobacterium avium<\/jats:italic>\n                    complex. We investigated the ability of\n                    <jats:sup>14<\/jats:sup>\n                    C-KRM\u20131648 to concentrate within human monocyte-derived macrophages\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . KRM\u20131648 is rapidly taken up by uninfected macrophages, with 90% of the initial concentration added to the monolayer found within macrophages by 1 h and approximately 80% at 2 h. Comparable results were obtained in assays using macrophages that have been infected with an AIDS-related strain of\n                    <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                    for 24 h. In contrast, macrophages infected with\n                    <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                    for 3 days, showed an impaired ability to concentrate KRM\u20131648, primarily because of a significant efflux of the antibiotic (intracellular concentration of 86% of the available drug was present within macrophages at 1 h vs. 47% at 2 h). Daily administration of KRM\u20131648 to a macrophage monolayer for 3 consecutive days resulted in significant accumulation of the drug within phagocytic cells. Although the efflux was greater in\n                    <jats:italic toggle=\"yes\">M. aviwm<\/jats:italic>\n                    -infected macrophages than in uninfected cells, consecutive administration of KRM\u20131648 led to a total intracellular accumulation of drug that exceeded the initial level and appeared to continue to accumulate. The ability of KRM\u20131648 to rapidly accumulate in human macrophages, including\n                    <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                    -infected cells, may explain, in part, the improved therapeutic effectiveness in animal models against\n                    <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1089\/mdr.1997.3.277","type":"journal-article","created":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T19:18:32Z","timestamp":1233256712000},"page":"277-282","source":"Crossref","is-referenced-by-count":3,"title":["Effect of\n                    <i>Mycobacterium avium<\/i>\n                    Infection on the Influx, Accumulation, and Efflux of KRM\u20131648 by Human Macrophages"],"prefix":"10.1177","volume":"3","author":[{"given":"Luiz E.","family":"Bermudez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark B.","family":"Inderlied","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2009,1,29]]},"container-title":["Microbial Drug Resistance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.1997.3.277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.1997.3.277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T12:21:23Z","timestamp":1775132483000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/mdr.1997.3.277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,10]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1997,10]]}},"alternative-id":["10.1089\/mdr.1997.3.277"],"URL":"https:\/\/doi.org\/10.1089\/mdr.1997.3.277","relation":{},"ISSN":["1076-6294","1931-8448"],"issn-type":[{"value":"1076-6294","type":"print"},{"value":"1931-8448","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,10]]}}}