In vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus

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.