{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:01:33Z","timestamp":1791298893632,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Simulating the average non-protein-bound (free) human serum drug concentration-time profiles for linezolid in an in vitro pharmacodynamic model, we characterized the pharmacodynamic parameter(s) of linezolid predictive of kill and for prevention of resistance in\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    . In 10-day dose-ranging studies, the average exposure for \u2265700 mg of linezolid given once daily (QD) resulted in &gt;3-log CFU\/ml declines in\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    without resistance selection. Linezolid at \u2264600 mg QD amplified for resistance. With twice-daily (q12h) dosing, linezolid at \u2265500 mg q12 h was required for resistance prevention. In dose fractionation studies, killing of\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    was predicted by the area under the time-concentration curve (AUC)\/MIC ratio. However, resistance prevention was linked to the maximum serum drug concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    )\/MIC ratio. Monte Carlo simulations predicted that linezolid at 1,100 mg QD would produce in 96.7% of human subjects a free 24-h AUC that would match or exceed the average 24-h AUC of 78.5 mg\u00b7h\/liter generated by linezolid at 700 mg QD while reproducing the shape of the concentration-time profile for this pharmacodynamically optimized regimen. However, linezolid at 700 mg q12h (cumulative daily dose of 1,400 mg) would produce an exposure that would equal or exceed the average free 24-h AUC of 90 mg\u00b7h\/liter generated by linezolid at 500 mg q12h in 93.8% of human subjects. In conclusion, in our in vitro studies, the QD-administered, pharmacodynamically optimized regimen for linezolid killed drug-susceptible\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    and prevented resistance emergence at lower dosages than q12h regimens. The lower dosage for the pharmacodynamically optimized regimen may decrease drug toxicity. Also, the QD administration schedule may improve patient compliance.\n                  <\/jats:p>","DOI":"10.1128\/aac.01439-07","type":"journal-article","created":{"date-parts":[[2008,5,5]],"date-time":"2008-05-05T20:34:22Z","timestamp":1210019662000},"page":"2486-2496","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Use of an In Vitro Pharmacodynamic Model To Derive a Linezolid Regimen That Optimizes Bacterial Kill and Prevents Emergence of Resistance in\n                    <i>Bacillus anthracis<\/i>"],"prefix":"10.1128","volume":"52","author":[{"given":"A.","family":"Louie","sequence":"first","affiliation":[{"name":"Ordway Research Institute, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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