IN VITRO AND IN VIVO ANTIBACTERIAL ACTIVITY OF BRL 28500 (CLAVULANIC ACID-TICARCILLIN)

• Published in: CHEMOTHERAPY Vol. 34; no. Supplement4; pp. 51 - 68
• Main Authors: OTSUKI, MASAKO, FUJIMOTO, CHIYOKO, NISHINO, TAKESHI, MORISHITA, MUTSUKO, TANINO, TERUO, KASAI, TAKAO
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1986; 公益社団法人 日本化学療法学会
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.34.Supplement4_51

Studies on the antibacterial activity of BRL 28500, a formulation of clavulanic acid (CVA) and ticarcillin (TIPC), have been performed and showed the following: 1) BRL 28500 had a similar antibacterial spectrum to TIPC against both Gram-positive and gramnegative bacteria although the antibacterial activity of BRL 28500 against clinical isolates was superior to TIPC and PIPC against strains of S. aureus, E. coli and K. pneumoniae, superior to TIPC against P. vulgaris and nearly equal to TIPC against H. influenzae and P. rettgeri. 2) A synergic action of CVA on the antibacterial activity of TIPC was observed by the checkerboard dilution method over a wide range of drug concentrations against both TIPC-sensitive and TIPC-resistant bacteria. 3) Against certain strains, the antibacterial activity of BRL 28500, like TIPC, decreased as the inoculum size was increased. Also as for TIPC, the antibacterial activity of BRL 28500 against certain strains decreased at alkaline pH, although to a lesser extent. The antibacterial activity of BRL 28500 was unaffected by the type of medium and horse serum used. 4) In a culture solution of TIPC-resistant bacteria, TIPC alone was rapidly decomposed whereas TIPC in BRL 28500 was quite stable under such conditions. This β-lactamase inhibitory activity of CVA was similarly recognized in the test with the extracted β-lactamase. 5) The blood concentration profiles of TIPC and CVA following administration of BRL 28500 to rats were quite similar. 6) When BRL 28500 acted against TIPC-resistant strains of E. coli and K. pneumoniae at a drug concentration around the MIC, spheroplasts in the elongated filament forms of the bacteria were seen here and there. 7) In treatment of experimental intraperitoneal infections in mice due to TIPC-resistant strains of S. aureus, E. coli, K. pneumoniae, P. vulgaris, P. mirabilis and H. influenzae. BRL 28500 exerted a beneficial therapeutic effect and at the site of such infections it was confirmed that in BRL 28500 substantial hydrolysis of the TIPC component did not occur.