Antibacterial activity and clinical studies on NM441 in urinary tract infections

Abstract

Fundamental and clinical studies of NM441, a new quinolone antimicrobial agent, were performed.
In the fundamental study, MICs of NM394, the active form of NM441, were examined against isolates obtained from patients with urinary tract infection and stored at our department and compared with those of ofloxacin, ciprofloxacin and tosufloxacin. Against gram-positive cocci (methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium), the MIC₉₀ of NM394 showed the highest values, 16μg/ml, against E. faecium. While, the MIC₉₀s of NM394 against gram-negative rods (Escherichia coli etc.) were 0.5μg/ml or less excluding 16μg/ml against Pseudomonas aeruginosa and 4μg/ml against Serratia marcescens.
In comparison with other drugs as the antibacterial activities against gram-positive cocci, the MIC₉₀ of NM394 was almost equal to those of the other drugs against MRSA and superior to those against E. faecium. In the activities against gram-negative rods, the MIC₉₀s of NM394 against S. marcescens and P. aeruginosa was superior to those of the other antimicrobial agents.
The clinical study was performed in the total of 26 patients, including 20 with acute uncomplicated cystitis (AUC) and 6 with chronic complicated cystitis (CCC). Efficacy evaluation was performed according to the criteria of Japanese UTI Committee, and 12 patients with AUC were determined to be eligible for the evaluation. The clinical efficacy rates were 100% in both patients treated with single administration and administration for 3 days. In the bacteriological efficacy, all 12 strains of causative organisms were eliminated. While, efficacy evaluation was performed according to the criteria of Japanese UTI Committee, and 5 patients with CCC were determined to be eligible for the evaluation. The evaluation at 5th day was excellent in 4, and the efficacy rates were 80%. In the bacteriological efficacy, all 8 strains of causative organisms were eliminated. However, E. faecalis and Candida tropicalis appeared after treatment in 1 patient.
Side effects were observed in 2 of 26 patients, mild headache and nausea, and skin rash in 1 patient each. Each symptom was disappeared by withdrawal.