STUDIES ON TA-058

Abstract

ntimicrobial activity of TA-058 was examined against gram negative rods from clinical materials in comparison with ABPC and PIPC. Minimum inhibitory concentrations of TA-058 against 41 strains of E. coli and 20 strains of K. pneumoniae were distributed from 0.8 to >200μg/ml and from 1.6 to >200 μg/ml respectively, showing similar activity to those of ABPC and inferior to those of PIPC. Minimum inhibitory concentrations against 21 strains of P. aeruginosa were distributed from 0.2 to 100μg/ml, showing superior activity to ABPC but inferior to PIPC.
Serum concentrations of TA-058, which resulted from the experiment with four healthy male adult volunteers who were administered 1g by drip infusion, reached their maxima immediately after the completion of infusion. Maximum serum concentration was 53.9μg/ml in average, half life in β-phase was 1.5 hrs., and AUC was 90.0 μg/ml·hr. On the other hand those parameters of ABPC, which was administered to the same subjects in crossed over design with TA-058, were 43.5μg/ml, 1.1 hrs. and 51.6μg/ml·hr., respectively. Urinary recovery of TA-058 up to 8 hours after the administration was 65.5% whereas that of ABPC was 67.6%. No abnormal change in blood sugar level was observed after the administration of either TA-058 or ABPC.
For the examination of clinical efficacy, TA-058 was administered to a case of biliary tract infection by drip infusion of 1g twice a day for 10 days. Improvement was observed both in subjective and objective observations thus impressed as fairly effective. No adverse clinical reaction was found, nor any abnormal laboratory findings in that case.