{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T18:41:06Z","timestamp":1794336066255,"version":"4.9.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2004,5,1]],"date-time":"2004-05-01T00:00:00Z","timestamp":1083369600000},"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":[[2004,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The effects of ceftizoxime (CZX), piperacillin (PIP), and PIP-tazobactam (PT) concentrations on the antibacterial activity and selection of resistant mutants of\n            <jats:italic>Bacteroides fragilis<\/jats:italic>\n            and\n            <jats:italic>Enterobacter cloacae<\/jats:italic>\n            were investigated in vitro in a mixed-culture anaerobic time-kill study and in vivo in a mixed-infection abscess model. Mixed cultures were incubated for 24 h with 0.125 to 512 \u03bcg of CZX per ml or 0.125 to 2,048 \u03bcg of PIP or PT per ml. Mice were treated every 2 h for 24 h with CZX at 6 to 1,536 mg\/kg\/day or with PIP or PT at 24 to 6,144 mg\/kg\/day starting 30 min before inoculation with different\n            <jats:italic>B. fragilis<\/jats:italic>\n            -\n            <jats:italic>E. cloacae<\/jats:italic>\n            combinations. There was a good correlation between the in vitro and in vivo activities of the antibiotics and their MICs obtained with high inocula (10\n            <jats:sup>8<\/jats:sup>\n            CFU\/ml). The respective 50% effective doses (milligrams per kilogram per day) with\n            <jats:italic>B. fragilis<\/jats:italic>\n            and\n            <jats:italic>E. cloacae<\/jats:italic>\n            22491 were 771 and 521 for CZX, 416 and 643 for PIP, and 85 and 554 for PT, and with the\n            <jats:italic>B. fragilis<\/jats:italic>\n            -\n            <jats:italic>E. cloacae<\/jats:italic>\n            032349 combination, they were 81 and 21 for CZX and 77 and 766 for PT. Resistant mutants of\n            <jats:italic>E. cloacae<\/jats:italic>\n            22491 were preferentially selected in vitro with 2 to 64 \u03bcg of CZX per ml and in vivo with CZX at 12 to 384 mg\/kg\/day. There was no preferential selection of CZX-resistant\n            <jats:italic>B. fragilis<\/jats:italic>\n            or\n            <jats:italic>E. cloacae<\/jats:italic>\n            032349. For CZX-resistant\n            <jats:italic>E. cloacae<\/jats:italic>\n            22491, we found a 16- to 512-fold increase in the MIC of CZX and increased MICs of other expanded-spectrum cephalosporins, owing in part to the production of a stably derepressed cephalosporinase. In vitro and in vivo, PT did not select resistant mutants of\n            <jats:italic>E. cloacae<\/jats:italic>\n            and\n            <jats:italic>B. fragilis<\/jats:italic>\n            . Results demonstrate the adverse microbiological outcome of choosing an expanded-spectrum cephalosporin like CZX for empirical treatment of mixed infections involving a susceptible\n            <jats:italic>Enterobacter<\/jats:italic>\n            strain.\n          <\/jats:p>","DOI":"10.1128\/aac.48.5.1688-1698.2004","type":"journal-article","created":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T19:58:16Z","timestamp":1082663896000},"page":"1688-1698","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Comparative Study of the Effects of Ceftizoxime, Piperacillin, and Piperacillin-Tazobactam Concentrations on Antibacterial Activity and Selection of Antibiotic-Resistant Mutants of\n            <i>Enterobacter cloacae<\/i>\n            and\n            <i>Bacteroides fragilis<\/i>\n            In Vitro and In Vivo in Mixed-Infection Abscesses"],"prefix":"10.1128","volume":"48","author":[{"given":"Lorna E. 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