Utilization of Bombyx mori larvae as a surrogate animal model for evaluation of the anti-infective potential of oxazolidinones

Abstract

Silkworm (Bombyx mori) larvae were investigated as an alternative animal model for the efficacy testing of novel oxazolidinones. The minimal lethal dose (MLD) for Staphylococcus aureus was 1-5 x 10(7) CFU per larva, exhibiting more than 90% mortality within 2 to 4 days post-infection. Treatment with vancomycin, linezolid, and novel oxazolidinones (RBx 7644, RBx 8700, and RBx 2006171) showed survival in a dose-dependent manner. The antibacterial potential of RBx 7644 and RBx 8700 was compared with that of linezolid and that of vancomycin and the effective doses (ED)50 obtained in the silkworm model were 37.89, 24.96, 13.38, and 30.72 mg/kg body weight, respectively. The ED50 values showed a similar trend in a murine model of infection. Owing to the small size of the larvae, very small amounts of new chemical entities (NCEs) are required to test their in vivo efficacy in this model. Thus, the silkworm model may be used in the early stage of new discovery research.