Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent in vitro and in vivo activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant Streptococcus pneumoniae. Patients with mild to moderate CAP (n ‫؍‬ 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.

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The in vitro antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better in vitro activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci, Neisseria gonorrhoeae, and Haemophilus influenzae. The in vitro activity of TG-875649 was also comparable to or better than that of moxifloxacin against these pathogens, which included ciprofloxacinresistant, methicillin-resistant Staphylococcus aureus and levofloxacin-resistant Streptococcus pneumoniae.

Our findings point to a potentially useful role for nemonoxacin in the treatment of infections caused by MSSA, ciprofloxacin-susceptible MRSA and S. pneumoniae with various resistance phenotypes.

Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with broad-spectrum activities againstGram-positive and Gram-negative aerobic, anaerobic, and atypical pathogens, as well as against methicillinresistant Staphylococcus aureus, vancomycin-resistant S. aureus, and multiple-resistant bacterial pathogens. We conducted a randomized, double-blind, placebo-controlled, dose-escalating study to ascertain the safety, tolerability, and pharmacokinetics of nemonoxacin. We enrolled 46 healthy volunteers and used a once-daily oral-dosing range of 75 to 1,000 mg for 10 days. Additionally, the food effect was evaluated in subjects in the 500-mg cohort. Nemonoxacin was generally safe and well tolerated, with no significant changes in the clinical laboratory tests or electrocardiograms. Adverse effects, including headache, contact dermatitis, and rash, were mild and resolved spontaneously. Nemonoxacin was rapidly absorbed within 2 h postdosing, and generally, a steady state was reached after 3 days. The maximum plasma concentration and the area under the plasma concentration-time curve were dose proportional over the dosing range. The elimination half-life was approximately 7.5 h and 19.7 h on days 1 and 10, respectively. Approximately 37 to 58% of the drug was excreted in the urine. Food affected the pharmacokinetics, with decreases in the maximum plasma concentration and area under the plasma concentration-time curve of 46% and 27%, respectively. However, the free AUC/MIC 90 of nemonoxacin was more than 100 under both the fasting and fed conditions, predicting the efficacy of nemonoxacin against most of the tested pathogens. In conclusion, the results support further clinical investigation of once-daily nemonoxacin administration for antibiotic-sensitive and antibiotic-resistant bacterial infections.Nemonoxacin (TG-873870) (31) is a novel nonfluorinated quinolone developed from a series of 8-methoxy nonfluorinated quinolones (25). It lacks the characteristic fluorine at the sixth position in fluoroquinolones (FQs) (Fig. 1). Nemonoxacin is a potent antibacterial agent with broad-spectrum activity against clinical isolates and reference strains in both in vitro studies and experimental infections in animals. It is active against Gram-positive, Gram-negative, and atypical pathogens, including penicillin-and quinolone-resistant Streptococcus pneumoniae (PRSP and QRSP), methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA (QR-MRSA), and vancomycin-resistant enterococci (4, 17). The nemonoxacin MIC 90 range is 0.06 to 1 g/ml for MRSA clinical isolates and 0.03 to 1 g/ml for PRSP clinical isolates from North America and Taiwan (17, 24, 33). For QR-MRSA clinical isolates, the MIC 90 range is 1 to 2 g/ml; this is 4-to 64-fold lower than the MIC 90 s of FQs in parallel testing, including ciprofloxacin, levofloxacin, and moxifloxacin (17, 24). There is increasing concern about vancomycin-intermediate S. aureus (VISA) among clinical isolates. Nemonoxacin showed an MIC 90 of 2 g/ml against heterogeneous VIS...