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JAC Advance Access originally published online on June 27, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):452-454; doi:10.1093/jac/dkl254
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Antibacterial activity of YC-20, a new oxazolidinone

Yingjie Cui1,*,{dagger}, Yaxian Dang1, Yushe Yang1,{dagger}, Shuhua Zhang2 and Ruyun Ji1

1 Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Sciences Shanghai 201203, China 2 Sichuan Industrial Institute of Antibiotics Chengdu 610051, China

*Corresponding author. E-mail: cuiyingjie{at}yahoo.com

Received 2 December 2005; returned 24 February 2006; revised 15 May 2006; accepted 26 May 2006


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Objectives and methods: YC-20 is a novel oxazolidinone that has targeted activity against Gram-positive bacteria. The in vitro activity of YC-20 and 6 comparators against 522 clinical isolates of Gram-positive species was determined.

Results: YC-20 is a potent oxazolidinone with all isolates tested displaying MIC50 and MIC90 values of <0.5 and 2 mg/L, respectively. MICs of YC-20 for all isolates tested, with the exception of methicillin-susceptible Staphylococcus epidermidis, were similar or lower than those of linezolid.

Conclusions: This study suggests a potential new antibiotic for the treatment of infections with Gram-positive bacteria.

Results: YC-20 is a potent oxazolidinone with all isolates tested displaying MIC50 and MIC90 values of <0.5 and 2 mg/L, respectively. MICs of YC-20 for all isolates tested, with the exception of methicillin-susceptible Staphylococcus epidermidis, were similar or lower than those of linezolid.

Conclusions: This study suggests a potential new antibiotic for the treatment of infections with Gram-positive bacteria.

Keywords: antibiotics , Gram-positive , linezolid


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A rapid expansion of antimicrobial resistance has led to the development of new antimicrobial agents. Oxazolidinones are a new class of totally synthetic antimicrobial agents active against multidrug-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), penicillin-resistant Streptococcus pneumoniae (PRSP) and vancomycin-resistant Enterococcus (VRE).1,2 Linezolid (see Figure 1), the first commercially available oxazolidinone, showed a broad activity against Gram-positive bacteria.3,4 During our research work on antibacterial agents, YC-20 (see Figure 1) was found to be a new oxazolidinone with enhanced activity against Gram-positive organisms.5


Figure 1
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  		Figure 1. Chemical structures of linezolid (1) and YC-20 (2).

 
The present study examines the in vitro antibacterial activity of YC-20 by comparing the MIC50 and MIC90 values with those obtained for linezolid, vancomycin, ampicillin, cefazolin, clarithromycin and levofloxacin against 522 isolates.


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Inclusion criteria: all microbiological samples between 2002 and 2003 were selected. Microscopy and culture data as well as susceptibility test results were analysed. A total of 522 strains were collected and identified at Sichuan Industrial Institute of Antibiotics by routine methodologies in use.

Antimicrobial susceptibility testing was performed using broth microdilution methods as described by the National Committee for Clinical Laboratory Standards (NCCLS).6 Linezolid was prepared as described previously.7 Other antimicrobial agents (vancomycin, ampicillin, cefazolin, clarithromycin and levofloxacin) were purchased from the National Institute for Control of Pharmaceutical and Biological Products. A total of 522 isolates were collected, comprising 200 S. aureus, 210 S. epidermidis, 20 Staphylococcus haemolyticus, 30 group A Streptococcus, 22 S. pneumoniae and 40 vancomycin-susceptible Enterococcus. Quality control measures were utilized by concurrently testing S. aureus ATCC 25923 and ATCC 29213.


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Results of microdilution MIC testing of the 522 isolates are presented in Table 1.


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  		Table 1. Antimicrobial activity of YC-20 against 522 Gram-positive organisms from clinical samples

 
The MICs of YC-20 ranged from 0.06 to 0.5 mg/L for methicillin-susceptible S. aureus (MSSA), from 0.25 to 0.5 mg/L for MRSA and from 0.125 to 2 mg/L for clarithromycin-resistant S. aureus. Among all groups of S. aureus, MICs of YC-20 were one or two dilutions lower than those of linezolid. Moreover, YC-20 showed better activity than six other antibiotics.

The MICs of YC-20 ranged from 0.03 to 0.5 mg/L for methicillin-susceptible S. epidermidis (MSSE), from 0.03 to 8 mg/L for MRSE and from 0.03 to 0.5 mg/L for clarithromycin-resistant S. epidermidis. YC-20 performed equally well or better against MRSE and clarithromycin-resistant S. epidermidis than did linezolid. In contrast, linezolid, ampicillin, cefazolin and levofloxacin showed better activity against MSSE than YC-20.

The MICs of YC-20 ranged from 0.03 to 0.5 mg/L for S. haemolyticus. Both YC-20 and linezolid performed similarly against S. haemolyticus. The two oxazolidinones exhibited better activity than other comparators except vancomycin.

For isolates of S. pneumoniae, MICs ranged from 0.125 to 0.5 mg/L for penicillin-susceptible strains compared with 0.25 to 4 mg/L for penicillin-resistant strains. MICs of YC-20 were two or four dilutions lower than those of linezolid. Activity of YC-20 against S. pneumoniae was weaker than that of vancomycin.

YC-20 was also active against group A streptococcal isolates with MICs of YC-20 being four dilutions lower than those of linezolid.

The MIC ranges observed for YC-20 and linezolid for vancomycin-susceptible Enterococcus were similar (0.25 to 0.5 mg/L).


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YC-20 and linezolid were active against all Gram-positive organisms isolated, including strains resistant to other classes of antibiotics. YC-20 exhibited MIC50 and MIC90 values of <0.5 and 2 mg/L against all isolates. Overall, the activity of YC-20 is slightly superior to that of linezolid. The present study confirms and expands previous findings of the good in vitro activity of YC-20 against Gram-positive organisms.5

YC-20 has a potential role in the treatment of infections caused by Gram-positive pathogens, especially for multidrug-resistant Gram-positive bacteria.


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None to declare.


   Footnotes
 
{dagger}These authors contributed equally to this study. Back


   Acknowledgements
 
We are thankful for the financial support from the National Natural Science Foundation of China (project 20272067).


   References
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1 Diekema DJ and Jones RN. (2000) Oxazolidinones: a review. Drugs 59:7–16.[CrossRef][Web of Science][Medline]

2 Woodford N. (2003) Novel agents for the treatment of resistant Gram-positive infections. Expert Opin Investig Drugs 12:117–37.[CrossRef][Web of Science][Medline]

3 Perry CM and Jarvis B. (2001) Linezolid: a review of its use in the management of serious Gram-positive infections. Drugs 61:525–51.[CrossRef][Web of Science][Medline]

4 Scrip Anonymous. (2000) The complete guide to anti-infectives. 2526:18.

5 Cui YJ, Yang YS, Chen KX, et al. (2003) Synthesis and antibacterial activity of oxazolidinone containing sulphonyl group. Bioorg Med Chem Lett 13:2311–3.

6 National Committee for Clinical Laboratory Standards. (1997) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically—Third Edition: Approved Standard M7-A4 (NCCLS, Villanova, PA, USA).

7 Brickner SJ, Hutchinson DK, Barbachyn MR, et al. (1996) Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant Gram-positive bacterial infections. J Med Chem 39:673–9.[CrossRef][Web of Science][Medline]


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This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
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