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  • Title: [Basic and clinical evaluation of sulbactam/cefoperazone in the field of pediatrics].
    Author: Toyonaga Y, Kurosu Y, Nakamura H, Sugita M, Takahashi T, Hori M.
    Journal: Jpn J Antibiot; 1984 Dec; 37(12):2457-77. PubMed ID: 6098740.
    Abstract:
    Sulbactam (SBT) in a novel beta-lactamase inhibitor from Pfizer and combined with cefoperazone (CPZ) ina 1:1 ratio (SBT/CPZ). Fundamental and clinical studies on SBT/CPZ were executed. The antibacterial activity of SBT/CPZ was compared with those of SBT, CPZ and CEZ against clinical isolates of S. aureus and E. coli which were not susceptible to CEZ. SBT alone did not show any activity against S. aureus, MICs against all strains were over than 100 micrograms/ml on the inoculations of undiluted and 100-fold diluted specimen. CPZ showed MICs over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, and on the 100-fold diluted inoculation, the MIC50 and MIC70 were 12.5 micrograms/ml and 100 micrograms/ml, respectively. SBT/CPZ showed better activity than CPZ by 2-8 folds against the strains highly resistant to CPZ; the MIC50 on the undiluted inoculation was 50 micrograms/ml. Against E. coli, the characteristic of SBT/CPZ was shown more clearly. The MICs of CPZ were over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, but SBT/CPZ showed MIC50 at 25 micrograms/ml. On the 100-fold diluted inoculation, SBT/CPZ was 4 approximately 8-fold superior than CPZ against strains on which MICs of CPZ were over than 12.5 micrograms/ml. Serum levels were determined by a bolus intravenous injection and by intravenous drip infusion of 10, 20, 40 mg/kg of SBT/CPZ. When administered by a bolus injection, the peak level was seen at 30 minutes in most patients: 8.7, 14.7 or 27.0 micrograms/ml of SBT and 30.1, 42.5 or 76.4 micrograms/ml of CPZ were detected with the 3 different doses. These levels were dose-dependent, and decreased slowly to 0.3, 0.3 or 0.3 micrograms/ml of SBT and 2.9, 2.8 or 3.3 micrograms/ml of CPZ at 6 hours after administration. Half-lives were 1.39, 1.20 or 0.98 hour for SBT and 1.77, 1.59 or 1.42 hours for CPZ. The same 3 doses were given by intravenous drip infusion. The peak levels obtained at the end of infusion (1 hour after initiation of infusion) were 15.3, 14.4 or 43.2 micrograms/ml for SBT and 33.4, 38.2 or 104.2 micrograms/ml for CPZ, respectively. The levels were somewhat low in 20 mg/kg group. After the end of infusion, these levels decreased fairly rapidly, and after 6 hours almost the same levels of 0.4, 0.5 or 0.3 micrograms/ml for SBT and 1.4, 3.9 or 3.3 micrograms/ml for CPZ were detected.(ABSTRACT TRUNCATED AT 400 WORDS)
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