In vitro antimicrobial activity of NM394, an active form of NM441, and therapeutic efficacy of NM441 in respiratory tract infections

The in vitro antimicrobial activity of NM394 was evaluated, and therapeutic efficacy of NM441, a new-quinolone agent for oral use developed in Japan which is a prodrug of NM394, were evaluated in the treatment of respiratory tract infections. The minimum inhibitory concentrations (MICs) of NM394, ofloxacin (OFLX), ciprofloxacin, tosufloxacin and rifampicin against 20 strains each of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa, 18 strains each of Enterobacter cloacae and Mycobacterium intracellular, 22 strains each of Mycobacterium tuberculosis and Mycobacterium avium, and 3 strains of Haemophilus influenzae were determined by the micro-broth dilution method using the Dynatech MIC2000 system. As shown by MICs, NM394 was as active as OFLX against all the species tested except for K. pneumoniae and P. aeruginosa. NM394 was the most active against K. pneumniae and P. aeruginosa among agents tested. Nine patients with pneumonia and 1 patient with diffuse panbronchiolitis received a dose of 100mg (3 cases), 200mg (6 cases) and 300mg (1 case) of NM441 twice a day per os for 10 to 14 days (mean; 13.6 days). The clinical effects were excellent in 2 and good in 8 patients (efficacy rate: 100%). Two strains each of Streptococcus pneumoniae and H. influenzae were identified as causative organisms. Three strains were eradicated and 1 strain of H. influenzae was persisted after therapy. No adverse reaction was observed during treatment with NM441. Transient elevation of serum transaminase was observed in 1 patient, but this adverse effect disappeared immediately after completion of therapy. We conclude from the above results that NM441 is one of the most useful quinolone agents for oral use as a drug of first choice in the treatment of respiratory infections.