1980 Volume 28 Issue Supplement6 Pages 489-512
Cefoperazone (CPZ, T-1551), a cephalosporin derivative, was examined on its in vitro anti-bacterial activity against bacteria isolated from human infection foci, as well as on its distribution in the body. Some clinical trials were also carried out. The results obtained were as follows:
1) In vitro antibacterial activity: As to Staphylococcus aurcus strains, CPZ was found to be superior to carbenicillin and piperacillin, but inferior to other cephalosporins examined (cefazolin, cephalothin, and cefmetazole). CPZ was found to have a great advantage of the activity against most of GNB, i.e. E. coli, Klebsiella pneumoniae, as well as Serratia and Pseudomonas aeruginosa. In addition, the drug has an distinctive feature: Hundred-fold dilution of the bacterial inoculum caused remarkable descent of MIC, thus rendering even resistant bacilli to quite sensitive. That is to say, the superiority of CPZ was magnified by the dilution of the inoculum.
2) Distribution in the body: A preliminary experiment revealed that the assay method using Micrococcus luteus ATCC 9341 as the test organism and the nutrient agar as the culture medium was appropriate for measurement of the drug concentration in body fluids. Rats administered with CPZ (20mg/kg or 100mg/kg im) showed highest concentration in the liver, followed by the blood, kidney and lung. Such a distribution pattern has never been seen hitherto in our studies on cephalosporins. One of the patients receiving drip infusion of CPZ (2g in 1.5 h.) showed serum concentration of 195μg/ml at the end of the infusion, and 14μg/ml 7.5 h. thereafter, the urinary excretion rate being 86% in 7.5 h.
3) Clinical trials: Thirteen patients (E. coli sepsis 1; R.T.I. 5; B.T.I. 5; U.T.I. 2) were treated with CPZ (2-4g/day, mostly by iv drip infusion) Those patients, excepting one, had some underlying disease. Eleven of them responded to the therapy, at least fairly. Neither clinical side effects nor changes in laboratory data attributable to the drug were observed, except for slight elevation of serum transaminases in one case.
These results obtained suggest that CPZ can be expected as an excellent new antibiotic for treatment of GNB infections.
