TA-058: Antimicrobial activity and clinical investigation on respiratory tract infections

In vitro antimicrobial activity of TA-058, a new derivative of ampicillin, was examined by a broth dilution method with Dynatech MIC 2,000 system. Also, therapeutic efficacy of TA-058 in the treatment of patients with respiratory tract infections was evaluated. The minimum inhibitory concentrations (MICs) of TA-058 were compared with those of piperacillin (PIPC) and sulbenicillin (SBPC) against following 20 strains each of clinical isolates; S. aureus, E. coli, K. pneumoniae, S. marcescens, P. aeruginosa. Although, TA-058 was more weakly active against these five species than piperacillin, TA-058 was more highly active against gram-negative rods, such as E. coli, K. pneumoniae, S. marcescens than sulbenicillin. TA-058 was almost as active as sulbenicillin against 5. aureus. TA-058 was given to a total of nine patients by an intravenous drip infusion. The subjects examined consisted of four patients of acute pneumonia, one patient with infection associated with bronchial asthma, one patient with diffuse panbronchiolitis, one patient with infection associated with pulmonary emphysema and two patients with infection associated with lung cancer. A daily dose of TA-058 given was 2 grams to four patients, 4 grams to four patients and 6 grams to one patient. Clinical response to the treatment with TA-058 was excellent in three patients, good in four patients and poor in two patients. Following six potential pathogens were recovered from the sputum of these patients at the start of the treatment with TA-058; three strains of H. influenzae, one strain each of 5. aureus, S. pneumoniae and K. pneumoniae. All of them but one strain of K. pneumoniae were eradicated during the treatment with the drug. In two patients among these nine patients, transient elevation of serum transaminase was observed but returned to normal after cessation of the drug.