Comparative study of BRL28500 (clavulanic acid-ticarcillin) and ticarcillin 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 (CVA) and 15 parts of ticarcillin (TIPC), using TIPC 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 1.6g of BRL (1.5g of TIPC plus 0.1g of CVA) or 1.5g of TIPC twice daily by intravenous drip infusion for 14 days in principle.BRL-treated group and TIPC-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 312 patients (BRL to 161 and TIPC to 151). Clinical efficacy was judged in 272 patients (138 on BRL and 134 on TIPC) excluding 40 patients from total patients by the committee. Incidence of side effects was evaluated in 289 patients (148 on BRL and 141 on TIPC) and abnormal changes in laboratory findings were assessed in 278 patients (141 on BRL and 137 on TIPC).2. The respective clinical efficacy rate for the BRL and the TIPC group was 78.8%, 75.0% in total patients and 74.6%, 79.1% in chronic RTI. No significant difference was observed between both treatment groups. However, the statistical analysis of patients with pneumonia or lung abscess showed that efficacy rate was 82.1% for the BRL group and 70.8% for the TIPC group respectively. BRL tended to be more effective than TIPC (p<0.10).3. As to clinical improvement of clinical symptoms and signs, improvement of ESR in the BRL group was better (p<0.10) than that in the TIPC group on 14th day after administration in patients with pneumonia or lung abscess. On the contrary, improvement of WBC and ESR in the BRL group was inferior (p<0.10) to those in the TIPC group on 3rd and 14th day after administration respectively in patients with chronic RTI.4. Bacteriological response was evaluated in 136 patients (68 each on BRL and TIPC) and eradication of causative organisms was 75.0% for the BRL group and 67.6% for the TIPC group, giving no statistical difference between both groups. However, there was a significant difference (p<0.05) in preference for BRL to TIPC in terms of eradication of H. influenzae (100% in BRL and 88.9% in TIPC) and all strains of Gram-negative bacilli (78.6% in BRL and 60.0% in TIPC).5. In 289 patients assessed incidence of side effects, five patients treated with BRL and seven patients treated with TIPC complained of side effects and there was no significant difference between both groups.6. Abnormal changes in laboratory findings were evaluated in 278 patients. Numbers of patients with the abnormal changes were 45 (31.9%) out of 141 patients treated with BRL and 32 (23.4%) out of 137 patients treated with TIPC respectively and the statistical difference was not significant between both groups.7. As to clinical utility judged by the committee taking into account of clinical efficacy and safety, the useful rate including “very useful” plus “useful” was 76.3% for the BRL group, 72.4% for the TIPC group in overall patients, 70.0% for the BRL group and 77.6 for the TIPC group in patients with chronic RTI, giving no siginificant difference between both groups. However, in patients with pneumonia or lung abscess the utility rate was 81.0% in the BRL group and 67.2% in the TIPC group respectively. BRL was more useful (p<0.10) than TIPC in these diseases.