In vitro antimicrobial activity of BRL 28500 and its therapeutic efficacy on lower respiratory infections

In vitro anitimicrobial activity of BRL 28500 which has a 15 : 1 composition of ticarcillin and clavulanic acid (a potent inhibitor of β-lactamases) was examined by a broth dilution method with Dynatech MIC 2000 system. Also, therapeutic efficacy on lower respiratory infections was evaluated. The minimum inhibitory concentrations(MlCs) of BRL 28500, ticarcillin and piperacillin respectively were determined against 20 clinical isolates each of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa. The results of determination of MICs indicated that BRL 28500 was more active than ticarcillin against all the species except for S. aureus, and as active as ticarcillin against S. aureus. As compared with piperacillin, BRL 28500 was as active as piperacillin against S. aureus, E. coli and K. pneumoniae, and somewhat less active than piperacillin against E. cloacae, S. marcescens and P. aeruginosa. A daily dose of 6.4 to 9.6 grams of BRL 28500 was given by drip infusion to a total of 15 cases which consisted of nine patients with pneumonia, two patients with bronchiectasis-associated infection and four patients with cancer associated infection of the lung. The clinical effects were excellent in five, good in six, fair in one and poor in three patients. A total of ten strains consisting of three strains of Streptococcus pneumoniae, one strain of Branhamella catarrhalis, four strains of Haemophilus influenzae and two strains of P. aeruginosa, were identified as causative organisms. All of them were eradicated by the treatment with BRL 28500. Drug induced fever occurred in one patient. An elevation of the values of serum transaminase was observed in two patients. These adverse reactions disappeared after completion of the therapy with BRL 28500. From the above results, it was concluded that BRL 28500 is one of the useful antibiotics for the treatment of lower respiratory tract infections.