{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:09:31Z","timestamp":1761127771582},"reference-count":26,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2001,10,1]],"date-time":"2001-10-01T00:00:00Z","timestamp":1001894400000},"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":[[2001,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The activity of ABT-773 was studied against extracellular and intracellular\n            <jats:italic>Legionella pneumophila<\/jats:italic>\n            and for the treatment of guinea pigs with\n            <jats:italic>L. pneumophila<\/jats:italic>\n            pneumonia. The ABT-773 MIC at which 50% of isolates are inhibited (MIC\n            <jats:sub>50<\/jats:sub>\n            ) for 20 different\n            <jats:italic>Legionella<\/jats:italic>\n            sp. strains was 0.016 \u03bcg\/ml, whereas the MIC\n            <jats:sub>50<\/jats:sub>\n            s of clarithromycin and erythromycin were 0.032 and 0.125 \u03bcg\/ml, respectively. ABT-773 (1 \u03bcg\/ml) was bactericidal for two\n            <jats:italic>L. pneumophila<\/jats:italic>\n            strains grown in guinea pig alveolar macrophages. In contrast, erythromycin and clarithromycin had easily reversible static activity only. Therapy studies of ABT-773 and erythromycin were performed with guinea pigs with\n            <jats:italic>L. pneumophila<\/jats:italic>\n            pneumonia. When ABT-773 was given to infected guinea pigs by the intraperitoneal route (10 mg\/kg of body weight), mean peak levels in plasma were 0.49 \u03bcg\/ml at 0.5 h and 0.30 \u03bcg\/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 0.55 h, and the area under the concentration-time curve from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ) was 0.65 \u03bcg \u00b7 h\/ml. For the same drug dose, mean levels in the lung were 15.9 and 13.2 \u03bcg\/g at 0.5 and 1 h, respectively, with a half-life of 0.68 h and an AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            of 37.0 \u03bcg \u00b7 h\/ml. Ten of 15\n            <jats:italic>L. pneumophila<\/jats:italic>\n            -infected guinea pigs treated with ABT-773 (15 mg\/kg\/dose given intraperitoneally once daily) for 5 days survived for 9 days post-antimicrobial therapy, as did 14 of 15 guinea pigs treated with erythromycin (30 mg\/kg given intraperitoneally twice daily) for 5 days. All of the ABT-773-treated animals that died appeared to do so because of drug-induced peritonitis rather than overwhelming pneumonia. None of 12 animals treated with saline survived. ABT-773 is as effective as erythromycin against\n            <jats:italic>L. pneumophila<\/jats:italic>\n            in infected macrophages and in a guinea pig model of Legionnaires' disease. These data support studies of the clinical effectiveness of ABT-773 for the treatment of Legionnaires' disease.\n          <\/jats:p>","DOI":"10.1128\/aac.45.10.2685-2690.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"2685-2690","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["In Vitro Activity of ABT-773 against\n            <i>Legionella pneumophila<\/i>\n            , Its Pharmacokinetics in Guinea Pigs, and Its Use to Treat Guinea Pigs with\n            <i>L. pneumophila<\/i>\n            Pneumonia"],"prefix":"10.1128","volume":"45","author":[{"given":"Paul H.","family":"Edelstein","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Pathology and Laboratory Medicine1 and"},{"name":"<!--label omitted: 2-->Medicine,2 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Higa","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Pathology and Laboratory Medicine1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha A. C.","family":"Edelstein","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Pathology and Laboratory Medicine1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.2.447-449.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/8.6.459"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.10.2895-2896.2000"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1894-1899.2000"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/clind\/21.Supplement_3.S265"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","unstructured":"Edelstein\n              P. H.\n          The guinea-pig model of Legionnaires' disease\n          Handbook of animal models of infection.\n              Zak\n              O.\n              Sande\n              M. 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