BACTERIOLOGICAL EVALUATION OF TA-058, A NEW SEMISYNTHETIC PENICILLIN

Abstract

In vitro and in vivo antibacterial activities of TA-058, a new semisynthetic penicillin, were compared with those of Carbenicillin (CBPC), Piperacillin (PIPC) and Apalcillin (APPC). The following results were obtained.
1. TA-058 showed a broad antibacterial spectrum against gram-positive and gram-negative bacteria which were maintained in Kyoto College of Pharmacy. The potency of TA-058 was similar to that of CBPC, but it was less than that of PIPC and APPC.
2. TA-058 exhibited stronger activity than PIPC and APPC against clinically isolated E. coil, H. influenzae and P. mirabilis, while it was slightly less active than CBPC against clinical isolates of P. aeruginosa.
3. TA-058 showed high bactericidal activities against E. coli and P. aeruginosa. The activities against E. coli at the higher concentrations over MIC of TA-058 were stronger than those of reference penicillins until 2 hours after the addition of drugs. The activities against E. coli were markedly higher than those of PIPC and APPC, especially when a large inoculum size (about 10⁸ cells/ml) was used. Against P. aeruginosa, the activity of TA-058 at a small inoculum size was similar to those of reference drugs, while at a large inoculum size, the activity was more potent than PLPC, equally to APPC and less than CBPC.
4. TA-058 excelled CBPC, PIPC and APPC in its therapeutic efficacy in experimental mice infections caused by E. coli, K. pneumoniae and P. aeruginosa. The excellence on the therapeutic effect was noted especially when a large challenge dose was used for the experiments.
5. When the drugs were administered to the mice with the infections, TA-058 gave higher serum and peritoneal fluid concentrations than those of PIPC.