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Comparative Study of the Effects of Ceftizoxime, Piperacillin, and Piperacillin-Tazobactam Concentrations on Antibacterial Activity and Selection of Antibiotic-Resistant Mutants of Enterobacter cloacae and Bacteroides fragilis In Vitro and In Vivo in Mixed-Infection Abscesses.
Lorna E. T. Stearne, 2004.The effects of ceftizoxime (CZX), piperacillin (PIP), and PIP-tazobactam (PT) concentrations on the antibacterial activity and selection of resistant mutants of Bacteroides fragilis and Enterobacter cloacae 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 µg of CZX per ml or 0.125 to 2,048 µg 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 B . fragilis-E . cloacae combinations . There was a good correlation between the in vitro and in vivo activities of the antibiotics and their MICs obtained with high inocula (10⁸ CFU/ml) . The respective 50% effective doses (milligrams per kilogram per day) with B . fragilis and E . cloacae 22491 were 771 and 521 for CZX, 416 and 643 for PIP, and 85 and 554 for PT, and with the B . fragilis-E . cloacae 032349 combination, they were 81 and 21 for CZX and 77 and 766 for PT . Resistant mutants of E . cloacae 22491 were preferentially selected in vitro with 2 to 64 µg of CZX per ml and in vivo with CZX at 12 to 384 mg/kg/day . There was no preferential selection of CZX-resistant B . fragilis or E . cloacae 032349 . For CZX-resistant E . cloacae 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 E . cloacae and B . fragilis . Results demonstrate the adverse microbiological outcome of choosing an expanded-spectrum cephalosporin like CZX for empirical treatment of mixed infections involving a susceptible Enterobacter strain .

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Last modified: May 25, 2005