JAC Advance Access originally published online on October 29, 2007
Journal of Antimicrobial Chemotherapy 2008 61(1):163-168; doi:10.1093/jac/dkm421
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Original research |
In vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus
1 Department of Microbiology, Kwandong University College of Medicine, Gangneung 210-701, South Korea 2 Department of Microbiology, Wonju College of Medicine, Yonsei University, 162 Ilsan-dong, Wonju 220-701, South Korea 3 Institute of Lifelong Health, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University, Wonju 220-701, South Korea
Received 1 May 2007; returned 16 July 2007; revised 28 August 2007; accepted 9 October 2007
* Corresponding author. Tel: +82-33-741-0323; Fax: +82-33-748-2709; E-mail: kim6{at}yonsei.ac.kr
Objectives: To verify in vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus, we compared antistaphylococcal activities of echinomycin with those of vancomycin.
Methods: In vitro activities (MICs and MBCs) of oxacillin, vancomycin and echinomycin against 18 isolates of methicillin-susceptible S. aureus (MSSA) and 118 isolates of methicillin-resistant S. aureus (MRSA) were compared. Using four representative isolates of S. aureus, time–kill assay and in vivo antistaphylococcal activities were assessed. Echinomycin and vancomycin were compared in an in vivo mouse infection model.
Results: Echinomycin demonstrated higher in vitro activities against MSSA and MRSA strains, exhibiting 2-fold lower MIC90s and 4-fold lower MBC90s than vancomycin. Additionally, time–kill assay indicated that echinomycin is more potent than vancomycin against MSSA and MRSA strains in the context of MICs and MBCs. Using an in vivo protection model, it was shown that the 50% effective doses of echinomycin were at least 7-fold lower than those of vancomycin. Therefore, echinomycin displayed excellent protection in mice against acute peritoneal infections caused by both MSSA and MRSA strains.
Conclusions: Collectively, these data indicate that the activity of echinomycin against S. aureus strains is at least equivalent to that of vancomycin, regardless of the methicillin resistance of these strains. These promising activities of echinomycin might justify its potential use against infections with S. aureus strains resistant to vancomycin. This might be the first report to show that echinomycin possesses antipathogenic staphylococcal activity.
Keywords: antistaphylococcal activities , vancomycin , methicillin resistance