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Guo-Qing Li, Min Yuan,
Xin-Yi Yang,
Cong-Ran Li,
Xin-Xin Hu,
Wei-Xin Zhang,
Ren-Hui Lou,
Hui-Yuan Guo,
Xuan-Wang You,
Shan Cen,
Jian-Dong Jiang,
Xue-Fu You
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ABSTRACT: Chinfloxacin is a novel synthetic fluoroquinolone with a structure similar to moxifloxacin. The in vitro activity of chinfloxacin was evaluated in the current study.
Chinfloxacin was tested against a total of 1,739 clinical isolates representing 23 species using the agar dilution method. Studies of bactericidal activity, including minimum bactericidal concentrations (MBC) and time-kill curve determinations, were conducted according to the recommendations of the Clinical and Laboratory Standards Institute.
Minimum inhibitory concentrations (MIC)(50)s and MIC(90)s of chinfloxacin were found to be the same or 2-fold lower than those of moxifloxacin against gram-positive isolates except for Streptococcus pyogenes (against which chinfloxacin showed similar MIC(50) as moxifloxacin but 2-fold higher MIC(90)), and the same as or 2-fold higher than those of moxifloxacin against gram-negative isolates. Chinfloxacin showed potent bactericidal activity with MBC/MIC ratios in the range of 1-2 for almost all the isolates tested. Time-kill curves further demonstrated chinfloxacin as a concentration-dependent bactericidal agent usually effective at concentrations of 2 MIC or higher.
Chinfloxacin showed similar in vitro activity as moxifloxacin.
Chemotherapy 06/2012; 58(3):175-84. · 1.82 Impact Factor
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Guo-Qing Li,
Xiao-Gang Bai,
Cong-Ran Li,
Xin-Yi Yang,
Xin-Xin Hu, Min Yuan,
Wei-Xin Zhang,
Ren-Hui Lou,
Hui-Yuan Guo,
Jian-Dong Jiang,
Xue-Fu You
[show abstract]
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ABSTRACT: To evaluate the in vivo antibacterial efficacy of chinfloxacin, a novel fluoroquinolone, in murine systemic and local infection models.
The efficacy of chinfloxacin in systemic infection was evaluated in a mouse peritonitis model using isolates of methicillin-susceptible Staphylococcus aureus (MSSA, n = 3), methicillin-resistant Staphylococcus aureus (MRSA; n = 1), penicillin-intermediate Streptococcus pneumoniae (PISP; n = 1), penicillin-resistant S. pneumoniae (PRSP; n = 2), vancomycin-susceptible Enterococcus faecalis (VSE; n = 1), vancomycin-resistant E. faecalis (VRE; n = 2), Escherichia coli (n = 3) and Klebsiella pneumoniae (n = 2). The local infections included mouse pulmonary infections caused by penicillin-susceptible S. pneumoniae (PSSP; n = 1), PRSP (n = 1) and K. pneumoniae (n = 2).
In the mouse systemic infection model, chinfloxacin demonstrated potent activity against MSSA [50% effective dose (ED(50)) 2.28-4.15 mg/kg], MRSA (ED(50) 14.75 mg/kg), PISP (ED(50) 6.20 mg/kg), PRSP (ED(50) 3.51-5.03 mg/kg), VSE (ED(50) 25.02 mg/kg), VRE (ED(50) 5.18-15.39 mg/kg), E. coli (ED(50) 1.25-1.90 mg/kg) and K. pneumoniae (ED(50) 2.92-8.28 mg/kg). The therapeutic efficacy of chinfloxacin was generally similar to (P > 0.05) that of moxifloxacin, significantly higher (P < 0.01 or P < 0.05) than that of levofloxacin in Gram-positive isolate infections (MSSA, MRSA, PISP, PRSP, VSE and VRE), and less than that of levofloxacin against E. coli and K. pneumoniae infections (P < 0.01). In the mouse pulmonary infection model, chinfloxacin showed potent activity towards S. pneumoniae (higher than levofloxacin and ciprofloxacin) and K. pneumoniae (lower than levofloxacin and similar to or higher than ciprofloxacin) infections.
The results validated the potent efficacy of chinfloxacin in vivo. The high efficacy of chinfloxacin in murine systemic and local infections warrants investigation of its clinical use.
Journal of Antimicrobial Chemotherapy 12/2011; 67(4):955-61. · 5.07 Impact Factor
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ABSTRACT: The susceptibilities of vertilmicin and seven reference aminoglycosides to modifications by six recombinant aminoglycoside-modifying enzymes, AAC(6')-Ie, APH(2'')-Ia, AAC(6')-Ie-APH(2'')-Ia, ANT(2'')-Ia, AAC(6')-Ib, and AAC(6')-Ib-cr, were studied by coupled spectrophotometric assays in microtiter plates. In comparison to other aminoglycosides, the susceptibility of vertilmicin was 45.8- to 250.0-fold lower for AAC(6')-Ie acetylation, 39.2- to 116.7-fold lower for AAC(6')-Ie-APH(2'')-Ia acetylation, and 1.8- to 7.5-fold lower for ANT(2'')-Ia adenylation (except that shown by amikacin) while relatively comparable for AAC(6')-Ib acetylation, AAC(6')-Ib-cr acetylation, APH(2'')-Ia phosphorylation, and AAC(6')-Ie-APH(2'')-Ia phosphorylation.
Antimicrobial Agents and Chemotherapy 06/2011; 55(8):3950-3. · 4.84 Impact Factor
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Cong-Ran Li,
Yi Li,
Guo-Qing Li,
Xin-Yi Yang,
Wei-Xin Zhang,
Ren-Hui Lou,
Jing-Fang Liu, Min Yuan,
Philip Huang,
Shan Cen,
Li-Yan Yu,
Li-Xun Zhao,
Jian-Dong Jiang,
Xue-Fu You
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ABSTRACT: 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.
Journal of Antimicrobial Chemotherapy 11/2010; 65(11):2411-5. · 5.07 Impact Factor
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Xue-Fu You,
Cong-Ran Li,
Xin-Yi Yang, Min Yuan,
Wei-Xin Zhang,
Ren-Hui Lou,
Yue-Ming Wang,
Guo-Qing Li,
Hui-Zhen Chen,
Dan-Qing Song,
Cheng-Hang Sun,
Shan Cen,
Li-Yan Yu,
Li-Xun Zhao,
Jian-Dong Jiang
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ABSTRACT: Vertilmicin is a novel aminoglycoside antibiotic with potent activity against gram-negative and -positive bacteria in vitro. In this study, we further evaluated the efficacy of vertilmicin in vivo in systemic and local infection animal models. We demonstrated that vertilmicin had relatively high and broad-spectrum activities against mouse systemic infections caused by Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The 50% effective doses of subcutaneously administered vertilmicin were 0.63 to 0.82 mg/kg, 0.18 to 0.29 mg/kg, 0.25 to 0.99 mg/kg, and 4.35 to 7.11 mg/kg against E. coli, K. pneumoniae, S. aureus, and E. faecalis infections, respectively. The therapeutic efficacy of vertilmicin was generally similar to that of netimicin, better than that of gentamicin in all the isolates tested, and better than that of verdamicin against E. coli 9612 and E. faecalis HH22 infections. The therapeutic efficacy of vertilmicin was further confirmed in local infection models of rabbit skin burn infection and mouse ascending urinary tract infection.
Antimicrobial Agents and Chemotherapy 08/2009; 53(10):4525-8. · 4.84 Impact Factor
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Cong-Ran Li,
Xin-Yi Yang,
Ren-Hui Lou,
Wei-Xin Zhang,
Yue-Ming Wang, Min Yuan,
Yi Li,
Hui-Zhen Chen,
Bin Hong,
Cheng-Hang Sun,
Li-Xun Zhao,
Zhuo-Rong Li,
Jian-Dong Jiang,
Xue-Fu You
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ABSTRACT: Vertilmicin is a new semisynthetic aminoglycoside with a structure similar to that of netilmicin except for a methyl group at the C-6' position. In the present study, the in vitro antibacterial activity of vertilmicin was studied, and its susceptibility to modifications by the recombinant aminoglycoside bifunctional modifying enzyme AAC(6')-APH(2'') was compared with those of verdamicin and netilmicin. A total of 1,185 clinical isolates collected from hospitals in Beijing between 2000 and 2001 were subjected to the in vitro antibacterial activity evaluations, including MIC, minimum bactericidal concentration (MBC), and time-kill curve tests. The MICs were evaluated in non-gentamicin-resistant (gentamicin-susceptible and gentamicin-intermediate) strains and gentamicin-resistant strains, respectively. For most of the non-gentamicin-resistant bacteria (except for the isolates of Pseudomonas spp.), the MIC(90)s of vertilmicin were in the range of 0.5 to 8 microg/ml, comparable to those of the reference aminoglycosides. For the gentamicin-resistant isolates, the three semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin) demonstrated low MIC(50)s and/or MIC(90)s, as well as high percent susceptibility values. Among the study drugs, vertilmicin showed the lowest MIC(90)s, 16 microg/ml, for the gram-positive gentamicin-resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis. Meanwhile, vertilmicin was a potent bactericidal agent, with MBC/MIC ratios in the range of 1 to 2 for Escherichia coli, Klebsiella pneumoniae, and S. aureus and 1 to 4 for S. epidermidis. The time-kill curve determination further demonstrated that this effect was rapid and concentration dependent. In evaluations of susceptibility to modifications by the recombinant AAC(6')-APH(2'') with maximum rate of metabolism/K(m) measurements, vertilmicin exhibited susceptibilities to both acetylation and phosphorylation lower than those of netilmicin and verdamicin.
Antimicrobial Agents and Chemotherapy 09/2008; 52(11):3875-82. · 4.84 Impact Factor
