{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:40:03Z","timestamp":1768488003685,"version":"3.49.0"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"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":[[2008,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            RWJ-54428 (also known as MC-02,479) is a new cephalosporin with promising activity against gram-positive bacteria. The pharmacodynamics (PDs) of RWJ-54428 against\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            ,\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            , and\n            <jats:italic>Enterococcus faecalis<\/jats:italic>\n            were studied in a neutropenic mouse thigh infection model. The RWJ-54428 MICs ranged from 0.25 to 1 mg\/liter. Mice with ca. 10\n            <jats:sup>6<\/jats:sup>\n            CFU\/thigh at the initiation of therapy were treated intraperitoneally with RWJ-54428 at doses that ranged from 3 to 1,200 mg\/kg of body weight\/day (in 2, 3, 4, 6, or 12 divided doses) for 24 h. The maximal reductions in bacterial counts in thigh tissues at 24 h for the methicillin-resistant\n            <jats:italic>S. aureus<\/jats:italic>\n            , penicillin-resistant\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            , and\n            <jats:italic>E. faecalis<\/jats:italic>\n            strains were \u22122.8, \u22123.8, and \u22121.7 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/thigh, respectively. The percentage of a 24-h dosing interval that the unbound serum RWJ-54428 concentrations exceeded the MIC (\n            <jats:italic>fT<\/jats:italic>\n            <jats:sub>&gt;<\/jats:sub>\n            <jats:sub>MIC<\/jats:sub>\n            ) was the pharmacokinetic (PK)-PD parameter that best described the efficacy of RWJ-54428. The\n            <jats:italic>fT<\/jats:italic>\n            <jats:sub>&gt;<\/jats:sub>\n            <jats:sub>MIC<\/jats:sub>\n            s for a bacteriostatic effect (no net change in the numbers of CFU\/thigh over 24 h) ranged from 14 to 20% for staphylococci and streptococci; for maximal reductions in the numbers of CFU\/thigh, the\n            <jats:italic>fT<\/jats:italic>\n            <jats:sub>&gt;<\/jats:sub>\n            <jats:sub>MIC<\/jats:sub>\n            s ranged from 22 to 36% for these strains. For\n            <jats:italic>E. faecalis<\/jats:italic>\n            , the ranges of\n            <jats:italic>fT<\/jats:italic>\n            <jats:sub>&gt;<\/jats:sub>\n            <jats:sub>MIC<\/jats:sub>\n            s for static and maximal effects were 30 to 46% and 55 to 60%, respectively. These data show that treatment with RWJ-54428 results in marked antibacterial effects in vivo, with the PK-PD parameters for efficacy being comparable to those for the efficacy of penicillins and carbapenems active against staphylococci and pneumococci.\n          <\/jats:p>","DOI":"10.1128\/aac.00776-07","type":"journal-article","created":{"date-parts":[[2007,10,22]],"date-time":"2007-10-22T23:00:48Z","timestamp":1193094048000},"page":"244-247","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacodynamics of RWJ-54428 against\n            <i>Staphylococcus aureus<\/i>\n            ,\n            <i>Streptococcus pneumoniae<\/i>\n            , and\n            <i>Enterococcus faecalis<\/i>\n            in a Neutropenic Mouse Thigh Infection Model"],"prefix":"10.1128","volume":"52","author":[{"given":"David C.","family":"Griffith","sequence":"first","affiliation":[{"name":"Microcide Pharmaceuticals, Inc. Mountain View, California 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Microcide Pharmaceuticals, Inc. Mountain View, California 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Microcide Pharmaceuticals, Inc. Mountain View, California 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael N.","family":"Dudley","sequence":"additional","affiliation":[{"name":"Microcide Pharmaceuticals, Inc. Mountain View, California 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/BF02480194","volume":"30","year":"1978","unstructured":"Akaike, A. C. 1978. Posterior probabilities for choosing a regression model. Ann. Inst. Math. Stat.30A:9-14.","journal-title":"Ann. Inst. Math. Stat."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2375"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.5.1422-1430.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF01997060","volume":"12","year":"1993","unstructured":"Craig, W. 1993. Relevance of animal models for clinical treatment. Eur. J. Clin. Microbiol. Infect. Dis.12(Suppl. 1):55-57.","journal-title":"Eur. J. Clin. Microbiol. Infect. 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