Laboratory studies and clinical evaluation of DL-8280 to the patients with respiratory infections

Laboratory and clinical studies on new synthetic antimicrobial agent “DL-8280” developed by Daiichi Seiyaku Co., Ltd., were performed and the following results were obtained. 1) Antimicrobial activity; The in vitro activity of “ DL-8280 “ was determined against 30 standard strains and 343 recent clinical isolates including 11 different species by a micro-broth dilution method using MIC 2000 (Dynatek) with inoculum size 105 CFU/ml except 104 CFU/ml of H. influenzae, and compared with those of nalidixic acid (NA), pipemidic acid (PPA) and norfloxacin (NFLX). As the results, “ DL-8280 “ showed excellent activity to both gram-negative bacilli and gram-positive cocci of standard strains. Furthermore, this was effective 16 to 64 times than that of NA or PPA against the all kinds of species of clinical isolates and so close to that of NFLX. “ DL-8280 “ was more active than NFLX against S. aureus, S. faecalis, H. influenzae and A. antitratus but less active against P. aeruginosa and E. cloacae. 2) Concentration levels of “ DL-8280 “ in serum and sputum; “ DL-8280 “ with doses of 200 and 400 mg were orally given to 6 patients with chronic respiratory infections in a cross-over manner and then concentration levels of this agent in serum and sputum were assayed microbiologically. Peak level of this drug in sputum was 4.13±2.48 μg/ml (200 mg of dosing) and 8.58± 2.48 μg/ml (400 mg of dosing), and each half life was 3.96 ± 0.77 hours and 4.11 ± 0.72 hours, respectively. On the other hand, peak level in sputum was 3.08 ± 1.35 μg/ml at a dosing of 200 mg and 5.22 ± 1.83 μg/ml at a dosing of 400 mg. The ratio of peak levels in sputum to those in serum showed higher than 70% and this suggested clinical usefulness of “ DL-8280 “ to the patients with respiratory infections. 3) Clinical results; Forty-two patients with respiratory infections were treated with “ DL-8280 “ at total doses of 1.6 to 8.4 g. Thirteen of these cases were suffering from pneumonia, 11 from an acute excerbation of chronic bronchitis, 11 from a secondary infection of bronchiectasis, 4 from diffuse panbronchiolitis and 3 from acute bronchitis, and main causative organisms were H. influenzae (15), S. pneumoniae (5) and P. aeruginosa (5). Out of 42 cases, clinical response was excellent in 6, good in 29, fair in 2 and poor in 4 cases respectively, and 1 case was not evaluable. As adverse reactions, gastric discomfort, anorexia and a slight dizziness was observed in one case respectively, and one patient had a transient slight elevation of GPT value in labora tory finding. Thus, “ DL-8280 “ is considered to be the useful drug for the treatment of the patients with the respiratory infections.