{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:16:54Z","timestamp":1791904614830,"version":"4.3.4"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"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":[[1999,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The activities of HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin for 97\n            <jats:italic>Legionella<\/jats:italic>\n            spp. isolates were determined by microbroth dilution susceptibility testing. Growth inhibition of two\n            <jats:italic>Legionella pneumophila<\/jats:italic>\n            strains grown in guinea pig alveolar macrophages was also determined. The concentrations required to inhibit 50% of strains tested were 0.06, 0.02, 0.25, 0.03, and 0.02 \u03bcg\/ml for HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin, respectively. BYE\u03b1 broth did not significantly inhibit the activities of the drugs tested, as judged by the susceptibility of the control\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            strain; however, when\n            <jats:italic>Escherichia coli<\/jats:italic>\n            was used as the test strain, levofloxacin activity tested in BYE\u03b1 broth was fourfold lower. HMR 3647, HMR 3004, erythromycin, and clarithromycin (0.25 and 1 \u03bcg\/ml) reduced bacterial counts of two\n            <jats:italic>L. pneumophila<\/jats:italic>\n            strains grown in guinea pig alveolar macrophages by 0.5 to 1 log\n            <jats:sub>10<\/jats:sub>\n            , but regrowth occurred over a 2-day period. HMR 3647, erythromycin, and clarithromycin appeared to have equivalent intracellular activities which were solely static in nature. HMR 3004 was more active than all drugs tested except levofloxacin. In contrast, levofloxacin (1 \u03bcg\/ml) was bactericidal against intracellular\n            <jats:italic>L. pneumophila<\/jats:italic>\n            and significantly more active than the other drugs tested. Therapy studies with HMR 3647 and erythromycin were performed in guinea pigs with\n            <jats:italic>L. pneumophila<\/jats:italic>\n            pneumonia. When HMR 3647 was given (10 mg\/kg of body weight) by the intraperitoneal route to infected guinea pigs, mean peak plasma levels were 1.4 \u03bcg\/ml at 0.5 h and 1.0 \u03bcg\/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.4 h. All 16\n            <jats:italic>L. pneumophila<\/jats:italic>\n            -infected guinea pigs treated with HMR 3647 (10 mg\/kg\/dose given intraperitoneally once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of HMR 3647 given twice daily. Fourteen of 16 erythromycin-treated (30 mg\/kg\/dose given intraperitoneally twice daily) animals survived, whereas 0 of 12 animals treated with saline survived. HMR 3647 is effective against\n            <jats:italic>L. pneumophila<\/jats:italic>\n            in vitro, in infected macrophages, and in a guinea pig model of Legionnaires\u2019 disease. HMR 3647 given once daily should be evaluated as a treatment for Legionnaires\u2019 disease in humans.\n          <\/jats:p>","DOI":"10.1128\/aac.43.1.90","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:08Z","timestamp":1539045248000},"page":"90-95","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["In Vitro Activity of the Ketolide HMR 3647 (RU 6647) for\n            <i>Legionella<\/i>\n            spp., Its Pharmacokinetics in Guinea Pigs, and Use of the Drug To Treat Guinea Pigs with\n            <i>Legionella pneumophila<\/i>\n            Pneumonia"],"prefix":"10.1128","volume":"43","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha A. C.","family":"Edelstein","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Pathology and Laboratory Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Agouridas\n              C.\n              Bonnefoy\n              A.\n              Chantot\n              J. F.\n          In vitro antibacterial activity of RU 004 a novel ketolide highly active against respiratory pathogens abstr. F158\n          Program and abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1995\n          140\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2149"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2137"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/BF01709263","article-title":"In vitro activity of the new ketolide HMR 3004 compared to an azalide and macrolides against Streptococcus pneumoniae and Haemophilus influenzae.","volume":"16","author":"Barry A. L.","year":"1997","unstructured":"Barry A. L. Fuchs P. C. Brown S. D. In vitro activity of the new ketolide HMR 3004 compared to an azalide and macrolides against Streptococcus pneumoniae and Haemophilus influenzae. Eur. J. Clin. Microbiol. Infect. Dis. 16 1997 767 769","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"e_1_3_2_6_2","unstructured":"Bornstein\n              N.\n              Behr\n              H.\n              Brun\n              Y.\n              Fleurette\n              J. In vitro activity of RU 004 on Legionella species abstr. F166\n          Program and abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1995\n          142\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_7_2","unstructured":"Bryskier\n              A.\n              Agouridas\n              C.\n              Chantot\n              J. F.\n          Ketolides: new semisynthetic 14-membered-ring macrolides\n          Expanding indications for the new macrolides azalides and streptogramins.\n              Zinner\n              S. H.\n              Young\n              L. S.\n              Acar\n              J.\n              Neu\n              H. C.\n          1997\n          39\n          50\n          Marcel Dekker Inc.\n          New York N.Y"},{"key":"e_1_3_2_8_2","unstructured":"Dupront\n              A.\n              Coussediere\n              D.\n              Lenfant\n              B.\n          Assay technique of HMR 3647 in human plasma\n          1997\n          1\n          56\n          Hoechst Marion Roussel\n          Romainville France"},{"key":"e_1_3_2_9_2","unstructured":"Dupront\n              A.\n              Lenfant\n              B.\n          Assay technique of HMR 3647 in human plasma. Addendum No. 5: 12 months stability of HMR 3647 in frozen plasma\n          1997\n          1\n          2\n          Hoechst Marion Roussel\n          Romainville France"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"S265","DOI":"10.1093\/clind\/21.Supplement_3.S265","article-title":"Antimicrobial chemotherapy for Legionnaires\u2019 disease: a review.","volume":"21","author":"Edelstein P. 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Dis."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.12.2132"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.1.180"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.31.12.3329-3330.1993"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.11.2387"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/jac\/37.1.117","article-title":"In-vitro activity of levofloxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia.","volume":"37","author":"Edelstein P. H.","year":"1996","unstructured":"Edelstein P. H. Edelstein M. A. C. Lehr K. H. Ren J. In-vitro activity of levofloxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia. J. Antimicrob. Chemother. 37 1996 117 126","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.2.314"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.11.2122"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1037"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1033"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/00005792-198903000-00005","article-title":"Disease due to the Legionellaceae (other than Legionella pneumophila). Historical, microbiological, clinical, and epidemiological review.","volume":"68","author":"Fang G.-D.","year":"1989","unstructured":"Fang G.-D. Yu V. L. Vickers R. M. Disease due to the Legionellaceae (other than Legionella pneumophila). Historical, microbiological, clinical, and epidemiological review. Medicine (Baltimore) 68 1989 116 132","journal-title":"Medicine (Baltimore)"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","unstructured":"Fitzgeorge R. B. S. Lever and A. Baskerville. 1993. A comparison of the efficacy of azithromycin and clarithromycin in oral therapy of experimental airborne Legionnaires\u2019 disease. J. Antimicrob. Chemother. 31 (Suppl. E):171\u2013176.","DOI":"10.1093\/jac\/31.suppl_E.171"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.11.2646"},{"key":"e_1_3_2_24_2","unstructured":"Garc\u0131\u0301a\n              I.\n              Pascula\n              A.\n              Ballesta\n              S.\n              Perea\n              E. J.\n          Uptake and intracellular activity of HMR 3647 in human phagocytic and nonphagocytic cells abstr. A-112\n          Program and abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1998\n          35\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.31.10.1529"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1172\/JCI110744","article-title":"Intracellular multiplication of Legionnaires\u2019 disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin.","volume":"71","author":"Horwitz M. A.","year":"1983","unstructured":"Horwitz M. A. Silverstein S. C. Intracellular multiplication of Legionnaires\u2019 disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin. J. Clin. Investig. 71 1983 15 26","journal-title":"J. Clin. Investig."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.2.454"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/jac\/27.3.343","article-title":"Inhibition of Legionella pneumophila in guinea pig peritoneal macrophages by new quinolone, macrolide and other antimicrobial agents.","volume":"27","author":"Kitsukawa K.","year":"1991","unstructured":"Kitsukawa K. Hara J. Saito A. Inhibition of Legionella pneumophila in guinea pig peritoneal macrophages by new quinolone, macrolide and other antimicrobial agents. J. Antimicrob. Chemother. 27 1991 343 353","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_29_2","unstructured":"Lenfant\n              B.\n              Sultan\n              E.\n              Wable\n              C.\n              Pascual\n              M. H.\n              Meyer\n              B. H.\n          Pharmacokinetics of 800-mg once-daily oral dosing of the ketolide HMR 3647 in healthy young volunteers abstr. A-49\n          Program and abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1998\n          16\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0732-8893(97)81806-8","article-title":"In vitro activity of clarithromycin alone and in combination with ciprofloxacin or levofloxacin against Legionella spp.: enhanced effect by the addition of the metabolite 14-hydroxy clarithromycin.","volume":"29","author":"Martin S. J.","year":"1997","unstructured":"Martin S. J. Pendland S. L. Chen C. Schreckenberger P. C. Danziger L. H. 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Dis."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.9.1733"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1196"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2099"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.8.1944"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.5.743"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.1.90","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.1.90","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:15:38Z","timestamp":1645460138000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.43.1.90"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,1]]}},"alternative-id":["10.1128\/AAC.43.1.90"],"URL":"https:\/\/doi.org\/10.1128\/aac.43.1.90","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,1]]},"assertion":[{"value":"1998-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}