Abstract
Basic and clinical studies were carried out on BRL25000, an antibacterial agent composed of a mixture of amoxicillin (AMPC) and clavulanic acid, a new β-lactamase inhibitor. The results of those studies were as follows.
(I) Antibacterial activity (MIC): The MICs of both BRL25000 and AMPC were determined for several species of bacteria, using clinical isolates. In the case of E. coli, the MIC distributions of both antibacterial agents showed a peak at 12.5 μg/ml, although the AMPC distribution showed a second peak as well. It was also found that strains which showed MICs of 200 μg/ml or more of AMPC were inhibited by lower BRL25000 concentrations, i. e., the MICs were 100 μg/ml or less with BRL25000. Thus, BRL25000 was shown to have superior antibacterial activity to AMPC against E. coli. The same patterns were found in the cases of P.mirabilis and indole Proteus sp. All of the tested K. pneumoniae strains were resistant to AMPC, whereas they all showed 100 μg/ml or less MICs of BRL25000. Both of these antibacterial agents were ineffective against all of the tested strains of Enterobacter sp. and P. aeruginosa. With regard to the S. marcescens strains, those which were resistant to AMPC showed lower MICs in relation to BRL25000, but there was no difference between these two antibacterial agents' MIC distributions against sensitive strains.
(II) Clinical results: A total of 17 patients diagnosed as having urinary tract infections were treated with BRL25000. In nine of these patients with acute uncomplicated cystitis, the results were excellent in eight cases and good in one case, for an efficacy rate of 100%. The remaining eight patients had complicated urinary tract infections, and the efficacy rate was 87.5%: four excellent cases, three good cases, and one poor case. The overall efficacy rate in these urinary tract infection cases was thus 94. 1%(16/17). The MICs of the clinical isolates obtained from these patients were also determined. In the effective cases, all of the isolates showed an MIC of 12.5μg/ml or less (using an inoculum level of 106 cells/ml). Therefore, a high degree of correlation was found between the clinical efficacy and the MICs of these causative organisms. The only side effects recorded were in one patient, who experienced a stomach discomfort and diarrhea.
