nemonoxacin and Pneumonia--Bacterial

Nemonoxacin , a novel non-fluorinated quinolone, exhibits potent activity against Gram-positive bacteria, including MRSA and fluoroquinolone-resistant MRSA, Gram-negative and atypical pathogens. This agent also has a reduced propensity for resistance development in many kinds of pathogens.. This article reviews currently available clinical and in vitro data that support the potential role of nemonoxacin for the treatment of common infectious diseases, including community-acquired pneumonia (CAP), Clostridium difficile infections (CDIs), acute bacterial skin and skin structure infections (ABSSSIs) and sexually transmitted diseases (STDs). One recent Phase II trial comparing either 500 mg or 750 mg oral nemonoxacin with 500 mg oral levofloxacin for mild to moderate CAP demonstrated that nemonoxacin had comparable clinical success with levofloxacin. Nemonoxacin showed lower MICs against clinical C. difficile isolates than commercially available fluoroquinolones, making it a potential therapeutic agent if novel formulations are developed to maintain a higher concentration in the human gut. For STDs, nemonoxacin also showed good activity against some common pathogens, such as Chlamydia trachomatis and Neisseria gonorrhoeae.. Although in vitro studies have shown promising results regarding the susceptibility to nemonoxacin of common pathogens causing CDIs, ABSSSIs and STDs, further clinical trials are needed to prove its efficacy.

Topics: Anti-Bacterial Agents; Chlamydia Infections; Clostridium Infections; Community-Acquired Infections; Drug Therapy, Combination; Gonorrhea; Humans; Levofloxacin; Pneumonia, Bacterial; Quinolones; Skin Diseases, Bacterial

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.. A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7-10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476.. A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (-3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (-8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05).. Nemonoxacin 500 mg once daily for 7-10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile. ClinicalTrials.gov identifier: NCT01529476.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Female; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Pneumonia, Bacterial; Quinolones; Safety; Treatment Outcome

To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial.. One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS).. The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred.. Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

Topics: Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Female; Haemophilus influenzae; Humans; Levofloxacin; Male; Middle Aged; Mycoplasma pneumoniae; Pneumonia, Bacterial; Quinolones; Streptococcus pneumoniae; Treatment Outcome; Young Adult

To evaluate the in vivo antibacterial efficacy of nemonoxacin, a novel C8-methoxy non-fluorinated quinolone in murine systemic and local infection models.. The efficacy of nemonoxacin in systemic infections was evaluated in mouse peritonitis models using isolates of methicillin-susceptible Staphylococcus aureus (MSSA, n=1), methicillin-resistant S. aureus (MRSA, n=1), methicillin- and levofloxacin-resistant Staphylococcus capitis (levofloxacin-resistant MRSC, n=1), penicillin-intermediate Streptococcus pneumoniae (PISP, n=1), penicillin-resistant S. pneumoniae (PRSP, n=2), Enterococcus faecalis (n=2, including 1 vancomycin-resistant Enterococcus, VRE) and Escherichia coli (n=3). The local infections included mouse pulmonary infections caused by PRSP (n=1), Klebsiella pneumoniae (n=1) and mouse ascending urinary tract infection caused by E. coli (n=1).. In the mouse systemic infection model, nemonoxacin demonstrated potent activity against MSSA (ED(50) =2.08 mg/kg), MRSA (ED(50) =2.59 mg/kg), levofloxacin-resistant MRSC (ED(50) =2.52 mg/kg), PISP (ED(50) =5.47 mg/kg), PRSP (ED(50) =3.68-5.28 mg/kg) and E. coli (ED(50) =3.13-5.28 mg/kg), and moderate activity towards E. faecalis infection (ED(50) =8.48-15.16 mg/kg). The therapeutic efficacy of nemonoxacin was significantly higher (P<0.01) than that of levofloxacin in infections caused by Gram-positive isolates (MSSA, MRSA, levofloxacin-resistant MRSC, PISP, PRSP and E. faecalis), but less potent than that of levofloxacin against E. coli infection (P<0.01). Nemonoxacin in vivo efficacy results with Gram-positive isolates (2- to 5-fold ED(50) advantage over levofloxacin) are consistent with the MIC data (4- to 16-fold MIC advantage of nemonoxacin over levofloxacin). In the mouse pulmonary infection model, nemonoxacin showed potent activity towards PRSP (higher than levofloxacin) and K. pneumoniae (lower than levofloxacin) infections. In the mouse ascending urinary tract infection model, nemonoxacin exhibited potent activity against E. coli infection (lower than levofloxacin).. The results validated the potent efficacy of nemonoxacin in vivo. The higher efficacy of nemonoxacin than of levofloxacin towards infections caused by Gram-positive cocci (especially MRSA, levofloxacin-resistant MRSC, PRSP and VRE) warrants investigation of its clinical use.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Male; Mice; Microbial Sensitivity Tests; Pneumonia, Bacterial; Quinolones; Treatment Outcome; Urinary Tract Infections