Antibacterial activity of NM394, the active form of prodrug NM441, a new quinolone

Abstract

The in vitro antibacterial activity of NM394 was compared with those of other new quinolones. NM394 showed potent and broad-spectrum antibacterial activity against 2,606 recent clinical isolates. The activity of NM394 against gram-positive bacteria was 2-to 16-fold less than that of tosufloxacin and sparfloxacin but was comparable to that of ofioxacin. Only against Streptococcus pyogenes was the activity of NM394 equal to that of sparfloxacin. Against gram-negative bacteria, NM394 showed antibacterial activity equal to that of ciprofloxacin. Against quinolone-resistant Pseudomonas aeruginosa (norfloxacin MIC, >6.25 p,g/ml), the activity of NM394 was greater than those of the other agents tested. NM394 was rapidly bactericidal at concentrations near the MIC. NM394 inhibited supercoiling activities of DNA gyrase purified from Staphylococcus aureus, Escherichia coli, and P. aeruginosa; the 50% inhibitory concentrations were 18.0, 0.41, and 2.05 ,ug/ml, respectively. (7), and OPC-17116 (3, 10), demonstrate more potent activity against gram-positive bacteria.-a]-quinoline-3-carboxylic acid} is the active form of prodrug NM441, a new fluoroquinolone antibacterial agent ( Fig. 1). In a previous report (11), the in vitro antibacterial activity of NM394 was studied in comparison with those of ciprofloxacin, ofloxacin, and enoxacin. Results indicated that NM394 had broad-spectrum antibacterial activity, including activity against gram-positive bacteria. In this study, we evaluated the in vitro activity of NM394 compared with those of other quinolones, including tosufloxacin and sparfloxacin.(Part of this work was presented previously [17]).MATERIALS AND METHODS Antimicrobial agents. NM394 was provided by Nippon Shinyaku Co., Ltd., Kyoto, and Meiji Seika Kaisya, Ltd., Tokyo, Japan. Other antimicrobial agents were provided as follows: norfloxacin, Kyorin Seiyaku Co., Ltd., Tokyo, Japan; ofloxacin, Daiichi Seiyaku Co., Ltd., Tokyo, Japan; ciprofloxacin, Bayer Yakuhin, Ltd., Osaka, Japan; tosufloxacin, Toyama Chemical Co., Ltd., Toyama, Japan; sparfloxacin, Dainippon Seiyaku Co., Ltd., Osaka, Japan; and methicillin and oxacillin, Banyu Seiyaku Co., Ltd., Tokyo, Japan.Test strains. The bacterial strains used in this study were collected between 1984 and 1991 from various hospitals in Japan and were maintained in our laboratory at -80°C in glycerol.Determination

In Vitro Antibacterial Activities of AF 3013, the Active Metabolite of Prulifloxacin, against Nosocomial and Community Italian Isolates

“…Against gram-negative bacteria (with the exception of Stenotrophomonas maltophilia and Acinetobacter isolates), AF 3013 was more active than ciprofloxacin and generally even more active than the other compared drugs. With reference to the earlier Japanese study (11), the comparison with ofloxacin and sparfloxacin for gram-positive bacteria and with ciprofloxacin for both gram-positive and gram-negative bacteria appears to be more in favor of AF 3013 for recently collected Italian isolates. Time-kill experiments using selected isolates confirmed that the bactericidal activity of AF 3013 was at least similar to that of ciprofloxacin.…”

“…Prulifloxacin and AF 3013 were developed in the late 1980s in Japan. The in vitro activity of AF 3013 has so far been investigated only in that country, against strains mostly isolated in the 1980s (11). At present, prulifloxacin is being considered for marketing in Italy and other European countries.…”

“…AF 3013, a fluoroquinolone formerly called NM394 (5,8,11), is the active compound derived from the transformation of the prodrug prulifloxacin (also called NM441 or AF 3012) after its oral administration and intestinal absorption. Prulifloxacin and AF 3013 were developed in the late 1980s in Japan.…”

“…Other fluoroquinolones, which had further-enhanced activity against gram-positive bacteria and were also variably active against anaerobes, were developed in the 1990s (10). However, several of these newer quinolones ended up being limited in their clinical use due to various, unexpected toxicity problems (1).AF 3013, a fluoroquinolone formerly called NM394 (5,8,11), is the active compound derived from the transformation of the prodrug prulifloxacin (also called NM441 or AF 3012) after its oral administration and intestinal absorption. Prulifloxacin and AF 3013 were developed in the late 1980s in Japan.…”

Randomized, Double-Blind Study of Prulifloxacin versus Ciprofloxacin in Patients with Acute Exacerbations of Chronic Bronchitis

“…In vitro studies have shown that prulifloxacin has a wide spectrum of antibacterial activity against gram-negative and gram-positive strains comparable to or higher than that of other reference drugs [8, 9]. …”