title: In vivo antibacterial activity of nemonoxacin, a novel non-fluorinated quinolone.
abstract: OBJECTIVE
  To evaluate the in vivo antibacterial efficacy of nemonoxacin, a novel C8-methoxy non-fluorinated quinolone in murine systemic and local infection models.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Cong-Ran
authors.initials: CR
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Li
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Yang
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Zhang
authors.forename: Ren-Hui
authors.initials: RH
authors.lastname: Lou
authors.forename: Jing-Fang
authors.initials: JF
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Yuan
authors.forename: Philip
authors.initials: P
authors.lastname: Huang
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Yu
authors.forename: Li-Xun
authors.initials: LX
authors.lastname: Zhao
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: You
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy; D015363:Quinolones / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones; C543520:nemonoxacin