Abstract
Fundamental and clinical studies on BRL 25000 granules were carried out in the pediatric field. BRL 25000 is a formulation comprising 1 part of clavulanic acid (CVA) and 2 parts of amoxicillin (AMPC).
The MICs of BRL 25000 and AMPC were assessed against 24 clinically isolated strains of S. aureus (including 23 β-lactamase producing strains), 22 S. pyogenes, 20 E. coli (8 β-lactamase producing strains), 24 K. pneumoniae (24 β-lactamase producing strains), 20 H. influenzae (6 β-lactamase producing strains). BRL 25000 showed MIC80 (cumulatively 80% of strains were inhibited) at 6.25 μg/ml against S. aureus, ≤0.10 μg/ml against S. pyogenes, 12.5 μg/ml against E. coli, 6.25 μg/ml against K. pneumoniae and 0.39 μg/ml against H. influenzae.
BRL 25000 showed no improvement in MIC terms against β-lactamase nonproducing strains compared with AMPC. However, BRL 25000 was markedly more effective against β-lactamase producing strains. Thus BRL 25000 was up to 8 fold more active against S. aureus, 2 to 64 fold against E. coli, 4 to 128 fold against K. pneumoniae, 4 to 16 fold against H. influenzae than AMPC.
Following oral administration of BRL 25000 granules (at a dose level of 12.5mg/kg) to 2 children aged 9 and 11 years, the mean peak serum concentrations of AMPC and CVA were 8.33±2.43 μg/ml and 4.44±1.65 μg/ml respectively 1 hour after dosing. The half-lives of AMPC and CVA were 1.35±0.42 hours and 0.91±0.05 hour, respectively.
The urinary excretion was 48.21±3.83% for AMPC and 16.90±7.06% for CVA in the first 6 hours after administration.
In clinical studies, 23 pediatric patients aged 2 months to 12 years with bacterial infections were treated with BRL 25000 granules and the clinical effectiveness, bacteriological response and side effects were evaluated.
The clinical response was assessed in 23 cases, 3 with acute rhinitis, 6 with acute purulent tonsillitis, 5 with acute bronchitis, 4 with acute pneumonia, 3 with impetigo, 1 with furunculosis and 1 with periproctal abscess. Results were excellent in 13 cases, good in 7, fair in 3 and hence the efficacy rate (excellent and good cases) was 87.0% (20/23). In paticular the clinical response in 9 cases with infections due to β-lactamase producing organisms was excellent in 6, good in 2, fair in 1 and the efficacy rate was 88.9% (8/9).
The bacteriological response was assessed against 4 strains of S. aureus (including 3 β-lactamase producing strains), 1 S. pyogenes, 7 H. influenzae (5 β-lactamase producing strains) and 1 K. pneumoniae (β-lactamase producing) which appeared to be causative organisms. Twelve strains were eradicated and 1 decreased (a β-lactamase producing H. influenzae) and hence the eradication ratio was 92.3% (12/13).
No side effects or abnormalities in laboratory findings were observed during the study.
