Efficacy of ME1036 against meticillin-resistant Staphylococcus aureus and vancomycin-insensitive S. aureus in a model of haematogenous pulmonary infection.

ME1036, a novel parenteral carbapenem, was developed for the treatment of meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). A model of haematogenous pulmonary infection was induced in mice by tail vein injection of MRSA strain NUMR101 or VISA Mu50 enmeshed in agar beads. After 24h of infection, mice were treated twice daily for 7 days with 200mg/kg/day vancomycin (VCM) or ME1036. Mice infected with VISA were also pre-treated with cyclophosphamide to induce an immunocompromised state. The number of viable bacteria in the lungs was counted 12h after the final drug treatment. VCM decreased the number of viable MRSA in the lungs in comparison with the control, although the difference was not significant (mean+/-standard error of the mean log(10) colony-forming units (CFU)/lung=6.876+/-0.54 vs. 8.25+/-0.41, respectively). In contrast, treatment with ME1036 resulted in a significant decrease in the number of viable MRSA (log(10)CFU/lung=2.69+/-0.44 (n=6); P3 log(10) reduction versus control against both MRSA strains (>5 log for the VCM-susceptible strain and 3.4 log for the VISA), whereas VCM produced