CHEMOTHERAPY
Online ISSN : 1884-5894
Print ISSN : 0009-3165
ISSN-L : 0009-3165
CLINICAL PHARMACOKINETICS OF SULBACTAM/CEFOPERAZONE IN INFECTED TISSUES FOLLOWING INTRAVENOUS ADMINISTRATION
Yoshimi NAKANISHIMasanori YOSHIMOTOHiroyuki NISHINDAIYoichi KASAIIkuo HASHIMOTOYasuo SAWADATakashi NAKAMURAJiroh MIKAMIMichiko SAITOHEiichi BEKKI
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1984 Volume 32 Issue Supplement4 Pages 379-391

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Abstract

Cefoperazone, a cephalosporin which inhibits most Enterobacteriacae, Pseudomonas aeruginosa and Staphylococcus aureus, is hydrolyzed by some β-lactamases. Combination drug of cefoperazone with β-lactamase inhibitor, sulbactam (SBT) for parenteral use, was administered to 18 hospitalized patients with infectious diseases: 6 with biliary tract infection, 6 with acute appendicitis, 2 with gastric ulcer, 1 with acute panperitonitis due to intestinal obstruction, 1 with necrosis of right lower leg due to arterial obstruction, 1 with cervical lymph cyst and 1 with fistula ani. Sulbactam/Cefoperazone (SBT/CPZ) in a dose of 1g was given by intravenous administration before or during operation. Tissue specimens of different sites were taken from the surgically removed organs. Samples of bile and purulent ascites were subsequently taken at intervals. SBT concentration was determined according to a cup bioassay method with Escherichia coil 603 (β-lactamase producing, CPZ high resistant) as the test organism. CPZ concentration was determined by bioassay with Micrococcus luteus ATCC 9341 as the test organism.
Concentrations of CPZ in the common duct bile increased quickly and reached high level, about 2, 000μg/ml and declined very slowly. In the cases of acute appendicitis and patients with purulent ascites, it is very interesting thing that SBT concentrations in ascites and appendix wall at the early time after SBT/CPZ injection, were higher than CPZ concentrations and CPZ concentration was higher than SBT concentration at 10 to 30 minutes after injection. The concentrations of SBT and CPZ in the infected tissues were higher than those in none infected tissues.
SET and CPZ concentrations in purulent ascites, common duct bile, gall bladder bile, gall bladder wall, infected appendix wall, pus in abscess and other infected tissues were observed higher than the MIC of CPZ and SBT/CPZ against Escherichia coil and Klebsiella pneumoniae bacilli, after 1 g of SBT/CPZ intravenous administration.
Sulbactam/Cefoperazone therefore will be a useful drug when used for chemotherapy of abdominal infectious diseases.

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© Japanese Society of Chemotherapy
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