Comparative study of BRL28500 (clavulanic acid-ticarcillin) and piperacillin in the treatment of respiratory tract infections

Abstract

A well-controlled comparative study was undertaken to assess the clinical efficacy and safety of BRL28500 (BRL), a formulation comprising one part of clavulanic acid and 15 parts of ticarcillin, using piperacillin (PIPC) as a reference drug in patients with respiratory tract infections (RTI).Patients with apparent clinical signs and symptoms of chronic RTI (chronic bronchitis, diffuse panbronchiolitis, infected bronchiectasis, infected pulmonary emphysema, infected pulmonary fibrosis and infected bronchial asthma), acute exacerbation of chronic RTI, bacterial pneumonia and lung abscess were administered 1.6 g of BRL (1.5 g of ticarcillin plus 0.1 g of clavulanic acid) or 2.0 g of PIPC twice daily by intravenous drip infusion for 14 days in principle.BRL-treated group and PIPC-treated group were compared in terms of clinical efficacy, improvement of clinical symptoms and signs, bacteriological response, incidence of side effects, abnormal changes in laboratory findings and utility. The following results were obtained:1. BRL and TIPC were administered to a total of 314 patients (BRL to 161 and PIPC to 153). Clinical efficacy was judged in 269 patients (138 on BRL and 131 on PIPC) excluding 45 patients from total patients by the committee.Incidence of side effects was evaluated in 293 patients (148 on BRL and 145 on PIPC) and abnormal changes in laboratory findings were asessed in 286 patients (141 on BRL and 145 on PIPC).2. Clinical efficacy rate for the BRL group and PIPC group was 78.8% and 79.4% in total cases, 82.1% (79 patients) and 79.5% (73 patients) in pneumonia and lung abscess and 74.6% (59 patients) and 79.3% (58 patients) in chronic RTI respectively. There was no statistically significant difference between the two groups.3. As to improvement of clinical symptoms and signs, improvement of ESR in the BRL group was better than that in the PIPC group on 14th day after administration in patients with pneumonia or lung abscess. On the contrary, improvement of rale, WBC and CRP in the BRL group was inferior to those in the PIPC group on 3rd day after administration in patients with chronic RTI. Significant differences were shown in these items between both groups.4. Bacteriological response was evaluated in 125 patients (68 on BRL and 57 on PIPC) and eradication of causative organisms was 75.0% for the BRL group and 71.9% for the PIPC group, giving no statistical difference between both groups. However, there was a significant difference in preference for BRL to PIPC in terms of eradication of Klebsiella spp. (87.5% for BRL and 16.7% for PIPC).When causative organisms were classified into two groups according to susceptibility to PIPC, eradication effect of PIPC (94.7%) was superior (p<0.10) to that of BRL (69.6%) in PIPC-sensitive organisms having 50μg/ml of MIC. On the other hand, in PICP-resistant organisms having 50μg/ml of MIC BRL exerted better eradication effect (66.7%) than PIPC (12.5%) and a significant difference was shown between the two groups.5. In 293 patients assessed incidence of side effects, five patients treated with BRL and eleven patients treated with PIPC complained of side effects and there was no significant difference between both groups.6. Abnormal changes in laboratory findings were evaluated in 286 patients. Numbers of patients with the abnormal changes were 45 (31.9%) out of 141 patients treated with BRL and 28 (19.3%) out of 145 patients treated with PIPC respectively and the difference was significant (p<0.05) between both groups. Itemized analysis showed that abnormal changes in GPT were found in 26 (18.6%) out to 140 patients treated with BRL and 14 (10.0%) out of 140 patients treated with PIPC and indicated that elevation of BUN were shown only in the PIPC group (4/127, 3.1%), giving tendency of significant difference (p<0.10) on the above items between the two groups.