1983 Volume 31 Issue Supplement3 Pages 156-164
Ceftazidime (CAZ, SN401) is a new semisynthetic cephalosporin, with marked resistance to β-lactamase, low MICs for gram-negative bacilli, and a broad spectrum of antibacterial activity against various species of pathogenic bacteria, including Haemophilus influenzae, Enterobacter cloacae Citrobacter freundii, Serratia marcescens, indole-positive Proteus, and Pseudomonas aeruginosa. The patients, 11 females and 6 males aged from 11 to 85 years, were treated with CAZ during the period from Aug.´81 to Feb.´82 in the Department of Surgery, Tenshi Hospital. The patients include 11 with acute peritonitis (10 due to acute appendicitis and 1 to cecal CROHN's disease), 5 with acute or subacute cholecystitis and cholangitis due to cholelithiasis, and 1 with fistula ani. 1 g of CAZ was given intravenously in 17 cases before operation. During the operation, blood, bile, ascites and tissue specimens were taken and these were sent to the Research Laboratories of Shin Nihon Jitsugyo Co., Ltd. for determination of CAZ concentration by microbioassay using Proteus mirabilis ATCC 21100 as the test organism.
The new knowledge obtained from this study on the CAZ concentrations in infected tissues is as follows:(i) Given at a dose of 1 g intravenously before opration, CAZ concentrations in common duct bile increased quickly in about 1 to 2 hours, reaching the maximum level of 24.5μg/ml, then declined slowly.(ii) CAZ penetrated into bile through gallbladder wall, in the cases of bile duct obstruction, and achieved comparatively high level quickly after injection.(iii) CAZ achieved high levels in gallbladder wall ranging from 17.5 to 42.2μg/g at 28 to 65 minutes after injection.(iv) In infected appendix wall, CAZ reached high levels quickly after injection.(v) Concentrations of CAZ in the gallbladder wall and appendixes, were directly proportional to the degree of the pathological changes of inflammation.(vi) The CAZ concentrations in purulent ascites, common duct bile, gal. lbladder bile, gallbladder wall, infected appendix, pus in the appendix and other infected tissues were higher than the MICs for Escherichia coli and Klebsiella pneumoniae after 1 g of CAZ intravenous administration.
Therefore, CAZ appears to be a very useful drug when used for chemotherapy of acute peritonitis, biliary tract infections and abdominal infectious diseases.
