Abstract
PC-904, a newly synthesized penicillin derivative (Sumitomo Chem, Lab.) was examined on its activity against bacteria isolated from human infection foci, serum levels and urinary excretion rates in humans after its administration, tissue concentrations in rats, as well as its effectiveness in clinical cases. The results obtained were as follows:
1) Antibacterial activity in vitro: Staphylococcus aureus, E. coli as well as Proteus mirabilis sho-wed similar sensitivity pattern against PC-904 to those against sulbenicillin or carbenicillin, although the number of the strains sensitive to the former was larger than those to the latters. Klebsiella strains were mostly resistant to PC-904, but, when the inoculum conc. was reduced to 106/ml, their MIC came down to 1.6-6.2μg/ml. The most remarkable advantage of PC-904 was found in its activity against Pseudomonas aeruginosa, i. e. the peak of MIC was located at 6.2μg/ml (inocul. conc. 106/ml) or 1.6-3.1μg/ml (106/ml).
2) Blood level and urinary excretion rates in humans: The peak levels of PC-904 in the plasma of three adult volunteers after single i. m. administration of 250 mg were found to be 36.5-37.1μg/ml, the urinary excretion rates being 30-40% in six hours after administration. Intravenous one shot injection of PC-904 to two adult volunteers yielded average blood levels as follows: 15 min. 233; 1/2 hr. 54.2; 1 hr. 40.2; 2 hr. 11.4; 3 hr. 9.3; 4 hr. 3.2μg/ml.
3) Tissue concentrations in rats: The organ levels of PC-904 30 min. after i. m. administration ranked in order of liver, kidneys, serum and lungs, being detectable from spleen and muscles.
4) Clinical trials: Two patients, one with U. T. I. complicated with S. L. E. and the other with pneumonia complicated with reticulosis, responded with good results to PC-904 therapy. Although no severe side effects were observed in those patients, the S. L. E. case yielded suspected drug fever in course of the therapy.
