{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:26:03Z","timestamp":1788639963493,"version":"build-2803163510"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"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":[[2004,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n S-3578 is a novel beta-lactam with enhanced activity against drug-resistant gram-positive cocci such as methicillin-resistant\n Staphylococcus aureus<\/jats:italic>\n (MRSA). We used murine penicillin-resistant\n Streptococcus pneumoniae<\/jats:italic>\n lung infection and neutropenic murine systemic MRSA infection models to determine the pharmacokinetic (PK)-pharmacodynamic (PD) parameter that best correlated with efficacy. Pharmacokinetic studies revealed that the maximum concentration in serum\/dose values for S-3578 and cefepime in plasma in the lung infection model were 1.21 to 1.54 and 0.97 to 1.29, respectively; those for S-3578 in plasma in the systemic infection model were 0.78 to 1.02. The area under the concentration-time curve (AUC)\/dose values for S-3578 and cefepime in plasma in the lung infection model were 0.98 to 1.13 and 0.77 to 1.04, respectively, and those for S-3578 in plasma in the systemic infection model were 1.03 to 1.11. The half-lives of S-3578 and cefepime in plasma in the lung infection model were 0.29 to 0.38 and 0.29 to 0.34, respectively, and those of S-3578 in plasma in the systemic infection model were 0.40 to 0.61. The time above the MIC was the PK-PD parameter that best correlated with efficacy in the murine lung infection model (\n \n R\n 2<\/jats:sup>\n <\/jats:italic>\n = 84 and 92% for S-3578 and cefepime in plasma, respectively). There was a twofold increase in the dose of S-3578 in the systemic infection model compared to that in the pneumonia model, yet the AUCs were the same. This may be due to the different MICs for the two pathogens.\n <\/jats:p>","DOI":"10.1128\/aac.48.2.378-383.2004","type":"journal-article","created":{"date-parts":[[2004,1,24]],"date-time":"2004-01-24T23:46:39Z","timestamp":1074987999000},"page":"378-383","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacodynamics of S-3578, a Novel Cephem, in Murine Lung and Systemic Infection Models"],"prefix":"10.1128","volume":"48","author":[{"given":"Shuichi","family":"Miyazaki","sequence":"first","affiliation":[{"name":"Department of Microbiology, Toho University School of Medicine, Omori-nishi, 5-21-16, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Toho University School of Medicine, Omori-nishi, 5-21-16, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakatsu","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Toho University School of Medicine, Omori-nishi, 5-21-16, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Toho University School of Medicine, Omori-nishi, 5-21-16, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/49.3.445"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/jac\/48.6.911","volume":"48","year":"2001","unstructured":"Betriu, C., M. Redondo, A. Boloix, M. Gomez, E. Culebras, and J. J. Picazo. 2001. Comparative activity of linezolid and other new agents against methicillin-resistant Staphylococcus aureus and teicoplanin-intermediate coagulase-negative staphylococci. J. Antimicrob. Chemother.48:911-913.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0732-8893(95)00053-D"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(20)30278-6"},{"key":"e_1_3_1_6_2","first-page":"481","volume":"238","year":"1953","unstructured":"Eagle, H., R. Fleischman, and M. Levy. 1953. Continuous vs. discontinuous therapy with penicillin. N. Engl. J. Med.238:481-488.","journal-title":"N. Engl. J. 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