{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T21:13:54Z","timestamp":1783890834125,"version":"3.55.0"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"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":[[2003,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible\n            <jats:italic>Enterococcus faecalis<\/jats:italic>\n            JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain,\n            <jats:italic>E. faecium<\/jats:italic>\n            HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 \u03bcg\/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 \u03bcg\/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [\n            <jats:sup>14<\/jats:sup>\n            C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg\/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of\n            <jats:italic>E. faecalis<\/jats:italic>\n            . Against\n            <jats:italic>E. faecium<\/jats:italic>\n            HB217, bacterial counts in vegetations significantly decreased during therapy (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01), and the effect was similar with GAR-936 at 14 mg\/kg b.i.d., 14 mg\/kg once a day (o.d.), and 7 mg\/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.\n          <\/jats:p>","DOI":"10.1128\/aac.47.1.216-222.2003","type":"journal-article","created":{"date-parts":[[2002,12,24]],"date-time":"2002-12-24T04:39:08Z","timestamp":1040704748000},"page":"216-222","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Activity and Diffusion of Tigecycline (GAR-936) in Experimental Enterococcal Endocarditis"],"prefix":"10.1128","volume":"47","author":[{"given":"Agne\u0300s","family":"Lefort","sequence":"first","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, EMI-U 9933"},{"name":"Universite\u0301 Paris VII, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Lafaurie","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, EMI-U 9933"},{"name":"Universite\u0301 Paris VII, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Massias","sequence":"additional","affiliation":[{"name":"Service de Pharmacie Clinique et des Biomate\u0301riaux"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolande","family":"Petegnief","sequence":"additional","affiliation":[{"name":"Service de Biophysique et de Me\u0301decine Nucle\u0301aire"},{"name":"Universite\u0301 Paris VII, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azzam","family":"Saleh-Mghir","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, EMI-U 9933"},{"name":"Universite\u0301 Paris VII, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudette","family":"Muller-Serieys","sequence":"additional","affiliation":[{"name":"Service de Microbiologie, Ho\u0302pital Bichat"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Le Guludec","sequence":"additional","affiliation":[{"name":"Service de Biophysique et de Me\u0301decine Nucle\u0301aire"},{"name":"Universite\u0301 Paris VII, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Fantin","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, EMI-U 9933"},{"name":"Universite\u0301 Paris VII, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.1.97-106.1997"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.8.2225-2229.2000"},{"key":"e_1_3_2_4_2","unstructured":"Craig W. A. and S. Gudmundsson. 1996. Postantibiotic effect p. 296-329. In V. Lorian (ed.) Antibiotics in laboratory medicine 4th ed. Williams and Wilkins Baltimore Md."},{"key":"e_1_3_2_5_2","first-page":"57","volume":"41","year":"1995","unstructured":"Englert, D., N. Roessler, A. Jeavons, and S. Fairless. 1995. Microchannel array detector for quantitative electronic radioautography. Cell. Mol. Biol. (Noisy-le-grand)41:57-64.","journal-title":"Cell. Mol. Biol. (Noisy-le-grand)"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(99)00092-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.10.2747-2751.2000"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.117.2.360-372.1974"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0732-8893(99)00090-5","volume":"35","year":"1999","unstructured":"Jones, R. N. 1999. 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