{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T02:18:05Z","timestamp":1776824285022,"version":"3.51.2"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[1998,10,1]],"date-time":"1998-10-01T00:00:00Z","timestamp":907200000000},"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":[[1998,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The purpose of this study was to evaluate the cerebrospinal fluid (CSF) pharmacodynamics of a new fluoroquinolone, gatifloxacin (AM-1155), in experimental pneumococcal meningitis. The penetration of gatifloxacin into CSF, calculated as the percentage of the area under the concentration-time curve (AUC) in CSF over the AUC in blood, was 46 to 56%. Gatifloxacin showed linear pharmacokinetics in CSF, and 1 h after intravenous dosages of 7.5, 15, or 30 mg\/kg of body weight, peak CSF concentrations were 0.46 \u00b1 0.08 (mean \u00b1 standard deviation), 0.94 \u00b1 0.16, and 1.84 \u00b1 0.5 \u03bcg\/ml, respectively. The elimination half-life of gatifloxacin in CSF was 3.8 to 5.6 h (compared with 2.7 to 3.2 h in blood). There was a significant interrelationship among the highest measured values of gatifloxacin in blood and CSF\/minimal bactericidal concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>peak<\/jats:sub>\n                    \/MBC), the time antibiotic concentrations exceeded the MBC (\n                    <jats:italic>T<\/jats:italic>\n                    &gt; MBC), and AUC\/MBC (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.94); in single-dose experiments, each correlated significantly with the bacterial killing rate. Divided-dose regimens, resulting in greater\n                    <jats:italic>T<\/jats:italic>\n                    &gt; MBC values but lower\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>peak<\/jats:sub>\n                    \/MBC ratios, were more effective in terms of bacterial clearance compared with corresponding single-dose regimens. Gatifloxacin therapy was as effective as currently recommended regimens (e.g., a combination of ceftriaxone and vancomycin) against this highly cephalosporin-resistant pneumococcal strain. The bactericidal activity of gatifloxacin in CSF was closely related to the AUC\/MBC ratio, but maximal activity was achieved only when drug concentrations exceeded the MBC for the entire dosing interval.\n                  <\/jats:p>","DOI":"10.1128\/aac.42.10.2650","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T20:29:31Z","timestamp":1539030571000},"page":"2650-2655","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Pharmacodynamics of Gatifloxacin in Cerebrospinal Fluid in Experimental Cephalosporin-Resistant Pneumococcal Meningitis"],"prefix":"10.1128","volume":"42","author":[{"given":"Irja","family":"Lutsar","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian R.","family":"Friedland","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loretta","family":"Wubbel","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia C.","family":"McCoig","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hasan S.","family":"Jafri","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winston","family":"Ng","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faryal","family":"Ghaffar","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"George H.","family":"McCracken","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->The University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.6.4.437"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.3.483"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199303000-00004"},{"key":"e_1_3_2_6_2","unstructured":"Gabrielson J. Weiner D. Parameter estimation Pharmacokinetic and pharmacodynamic data analysis: concepts and applications 2nd ed. Gabrielson J. Weiner D. 1997 31 57 Swedish Pharmaceutical Press Stockholm Sweden"},{"key":"e_1_3_2_7_2","unstructured":"Hopkins S. Williams D. Dunne M. Marinovich L. Edeline M. Utt E. Dutse A. I. A randomized controlled trial of oral or IV trovafloxacin vs. ceftriaxone in the treatment of epidemic meningococcal meningitis abstr. LB-21. Presented at the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy 1996"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/36.2.293"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.10.2108"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1186"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.3.627"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.12.2635"},{"key":"e_1_3_2_13_2","unstructured":"National Committee for Clinical Laboratory Standards Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically 3rd ed. Approved standard. NCCLS publication no. 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