BRl25000 (Clavulanic Acid-Amoxicillin) Antimicrobial Activity And Clinical Investigation On Respiratory Tract Infections

The antimicrobial activity of BRL25000 which has a composition of 2 : 1 of amoxicillin and clavulanic acid, a potent inhibitor of many ²-lactamases, was examined by a broth dilution method using the Dynatech MIC-2000 system. Also, the therapeutic efficacy of BRL25000 in the treatment of patients with respiratory tract infections was evaluated. The minimum inhibitory concentrations (MICs) of BRL25000 were compared with those of amoxicillin(AMPC)and clavulanic acid(CVA)against 20 strains of each of the following clinical isolates : Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa. Reductions in the MICs of AMPC in the presence of CVA were marked for S. aureus, ²-lactamase producing strains of E. coli and K. pneumoniae, but to a less extent for E. cloacae, S. marcescensand P. aeruginosa. A daily dose of 1,500 milli-grams of BRL25000 was given orally to a total of five patients with respiratory tract infections. The subjects examined consisted of one patient with acute pneumonia, one patient with infection associated with bronchiectasis and three patients with infection associated with lung cancer. Clinical response to the treatment with BRL25000 was excellent in two patients, good in two and poor in one. The following four potential pathogens were recovered from the sputum of these patients at the start of the treatment with BRL25000: three strains of Haemophilus influenzae and one strain of Klebsiella pneumoniae. Three of the strains were eradicated during the treatment with the drug. In one of these five patients, transient diarrhea was observed but disappeared after cessation of the drug.