{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:08:36Z","timestamp":1790507316275,"version":"4.1.0"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[1997,11,1]],"date-time":"1997-11-01T00:00:00Z","timestamp":878342400000},"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":[[1997,11]]},"abstract":"<jats:p>Adequate concentrations of beta-lactam antibiotics in cerebrospinal fluid (CSF) are difficult to achieve for meningitis caused by drug-resistant Streptococcus pneumoniae. Ceftriaxone in dosages of 150 or 400 mg\/kg of body weight per day, given in one or two doses, was used for the treatment of experimental highly cephalosporin-resistant (MIC and MBC, 4 microg\/ml) pneumococcal meningitis. The bacterial killing rate (delta log10 CFU per milliliter per hour) and pharmacokinetic indices, including percentage of time the antibiotic concentration exceeded the MBC during a 24-h period (T&gt;MBC), CSF peak concentration above the MBC, and area under the concentration-time curve from 0 to 24 h above MBC, were measured and correlated. By multiple stepwise regression, only T&gt;MBC independently predicted the bacterial killing rate. There was a direct linear correlation between T&gt;MBC in CSF and the bacterial killing rate during the first 24 h of therapy (r = 0.87; P = 0.004). Sterilization of CSF was achieved only when the T&gt;MBC was 95 to 100%. In the first 24 h, the 200-mg\/kg\/12-h regimen, compared with the 400-mg\/kg\/24-h regimen, was associated with a greater T&gt;MBC (87% +\/- 10% versus 60% +\/- 22%; P = 0.03) and greater bacterial killing rate (0.2 +\/- 0.04 versus 0.13 +\/- 0.07; P = 0.003), confirming that ceftriaxone exhibits time-dependent bactericidal activity. After 24 h, the T&gt;MBC and the CSF sterilization rates were similar whether ceftriaxone was given once or twice daily.<\/jats:p>","DOI":"10.1128\/aac.41.11.2414","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:27:12Z","timestamp":1539044832000},"page":"2414-2417","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Pharmacodynamics and bactericidal activity of ceftriaxone therapy in experimental cephalosporin-resistant pneumococcal meningitis"],"prefix":"10.1128","volume":"41","author":[{"given":"I","family":"Lutsar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I R","family":"Friedland","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Trujillo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Wubbel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"G H","family":"McCracken","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Southwestern Medical Center, Dallas, Texas 75235-9063, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.41.11.2414","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.41.11.2414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:10:17Z","timestamp":1645474217000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.41.11.2414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,11]]},"references-count":0,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1997,11]]}},"alternative-id":["10.1128\/AAC.41.11.2414"],"URL":"https:\/\/doi.org\/10.1128\/aac.41.11.2414","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,11]]},"assertion":[{"value":"1997-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}