{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:04:50Z","timestamp":1792717490980,"version":"4.5.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2005,3,1]],"date-time":"2005-03-01T00:00:00Z","timestamp":1109635200000},"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":[[2005,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000 mg of amoxicillin\/125 mg of clavulanate twice a day; ratio 16:1) has been designed, with sustained-release technology, to allow coverage of bacterial strains with amoxicillin-clavulanic acid MICs of at least 4\/2 \u03bcg\/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000\/125 mg twice a day, ratio 16:1, was compared in a rat model of respiratory tract infection versus four other amoxicillin-clavulanate formulations: 8:1 three times a day (1,000\/125 mg), 7:1 three times a day (875\/125 mg), 7:1 twice a day (875\/125 mg), and 4:1 three times a day (500\/125 mg); levofloxacin (500 mg once a day); and azithromycin (1,000 mg on day 1 followed thereafter by 500 mg once a day). Bacterial strains included\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            , with amoxicillin-clavulanic acid MICs of 2\/1 (one strain), 4\/2, or 8\/4 \u03bcg\/ml (three strains each), and\n            <jats:italic>Haemophilus influenzae<\/jats:italic>\n            , one \u03b2-lactamase-positive strain and one \u03b2-lactamase-negative, ampicillin-resistant strain. Animals were infected by intrabronchial instillation. Antibacterial treatment commenced 24 h postinfection, with doses delivered by computer-controlled intravenous infusion to approximate the concentrations achieved in human plasma following oral administration. Plasma concentrations in the rat corresponded closely with target human concentrations for all antimicrobials tested. Amoxicillin-clavulanate, 2,000\/125 mg twice a day, ratio 16:1, was effective against all\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            strains tested, including those with amoxicillin-clavulanic acid MICs of up to 8\/4 \u03bcg\/ml and against \u03b2-lactamase-producing and \u03b2-lactamase-negative ampicillin-resistant\n            <jats:italic>H. influenzae<\/jats:italic>\n            . These results demonstrate the bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate 2,000\/125 mg twice a day (ratio 16:1) against\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            with amoxicillin-clavulanic acid MICs of at least 4\/2 \u03bcg\/ml and support clavulanate 125 mg twice a day as sufficient to protect against \u03b2-lactamase in this rat model.\n          <\/jats:p>","DOI":"10.1128\/aac.49.3.908-915.2005","type":"journal-article","created":{"date-parts":[[2005,2,23]],"date-time":"2005-02-23T22:51:53Z","timestamp":1109199113000},"page":"908-915","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against\n            <i>Streptococcus pneumoniae<\/i>\n            with Elevated Amoxicillin MICs and\n            <i>Haemophilus influenzae<\/i>"],"prefix":"10.1128","volume":"49","author":[{"given":"Valerie","family":"Berry","sequence":"first","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hoover","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Singley","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Woodnutt","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2385"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.12.3193"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/45.suppl_3.79"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2256"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/jac\/26.3.371","volume":"26","year":"1990","unstructured":"Cooper, C. 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