Celotiam (SCE-963), a new cephalosporin derivative developed by Takeda Chemical, was examined on its antibacterial activity, as well as on its distribution in rats. Some clinical trials were also carried out. The results obtained were as follows:
1) Antibacterial activity: The MIC distribution of cefotiam against clinical isolates of S. aureus was similar to cephaloridine, cephalothin, and cefazolin. Clinical isolates of E. coli were found to be much more sensitive to cefotiam than to other cephalosporins, especially when the inoculums were diluted to 106 cells/ml. Out of thirteen strains of Klebsiella only one was highly resistant (MIC≥100 μg/ml) to cefotiam
while four to cefazolin, six to cephalothin, and seven to cephaloridine. Although MIC of cefotiam against Proteus mirabilis were distributed in a wide range (0.1-100 μg/ml), most of them shifted to lower concentrations (0.1-0.4 μg/ml) by diluting the inoculum to 106/ml. Similar phenomenon was also observed on the s ensitivity of P. vulgaris and P. rettgeri, but these strains were essentially insensitive to the drug.
2) Tissue concentrations in rats: Tissue levels of cefotiam after i. m. administration of 10 mg/kg rankedin order of kidneys, liver, serum, lungs and spleen. The drug was undetectable in muscles as well as in the brain. In vitro recovery of the drug from organ emulsions of rats was found to be almost 100%.
3) Clinical trials: Nine patients with infections (4 with U. T. I., 3 with pulmonary infections, 1 with cholecystitis, and another with F. U.O.) weie treated with the drug. Five of the patients well responded to the therapy. Although no severe side effects were observed, rash was encountered in two of the patients, and disorder of liver function was observed in two of them.
