{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:17:18Z","timestamp":1790911038399,"version":"4.1.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"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":[[2004,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We evaluated the impact of high (9.5 log\n                    <jats:sub>10<\/jats:sub>\n                    CFU\/g) and moderate (5.5 log\n                    <jats:sub>10<\/jats:sub>\n                    CFU\/g) inocula of methicillin-susceptible and -resistant S\n                    <jats:italic>taphylococcus aureus<\/jats:italic>\n                    (MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 \u00b1 1.1, 3.28 \u00b1 0.4, and 3.34 \u00b1 0.8 log\n                    <jats:sub>10<\/jats:sub>\n                    CFU\/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 \u00b1 0.10 log\n                    <jats:sub>10<\/jats:sub>\n                    CFU\/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01) and 48 h for nafcillin (MSSA only) (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    had a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.\n                  <\/jats:p>","DOI":"10.1128\/aac.48.12.4665-4672.2004","type":"journal-article","created":{"date-parts":[[2004,11,23]],"date-time":"2004-11-23T22:00:46Z","timestamp":1101247246000},"page":"4665-4672","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":260,"title":["Impact of High-Inoculum\n                    <i>Staphylococcus aureus<\/i>\n                    on the Activities of Nafcillin, Vancomycin, Linezolid, and Daptomycin, Alone and in Combination with Gentamicin, in an In Vitro Pharmacodynamic Model"],"prefix":"10.1128","volume":"48","author":[{"given":"Kerry L.","family":"LaPlante","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences"},{"name":"School of Medicine, Wayne State University, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1925-1929.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.454-459.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.8.2606-2612.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1251-1256.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.11.3484-3489.2002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/20.2.213"},{"key":"e_1_3_2_8_2","first-page":"11","volume":"46","year":"2004","unstructured":"Anonymous. 2004. 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