Potency of DX-619, a novel des-F(6)-quinolone, in haematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus

Abstract

In this study, the potency of DX-619, a novel des-fluoro(6)-quinolone agent, was compared with that of vancomycin (VCM) in a murine model of haematogenous bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). The minimum inhibitory concentrations (MICs) of DX-619 and VCM against MRSA were 0.03 μg/mL and 1.0 μg/mL, respectively, whilst the MICs against VISA were 0.125 μg/mL and 8.0 μg/mL, respectively. Treatment with DX-619 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (mean ± standard error of the mean for control, VCM and DX-619 groups: 7.97 ± 0.32, 7.19 ± 0.33 and 2.91 ± 0.60 log 10 colony-forming units/lung, respectively). For infection with VISA, mice were pre-treated with cyclophosphamide. The survival rate of mice treated with DX-619 (90% survival) was significantly higher than survival rates in the other two groups (45% both for VCM and control groups; P < 0.05). Histopathological examination revealed that inflammatory changes in the DX-619-treated group were less marked than in the other two groups. The parameters in lung tissue for the area under the concentration–time curve/MIC ratio both for MRSA and VISA were higher in the DX-619 group than in the VCM group. Our results emphasise the potency of DX-619 against MRSA and VISA murine haematogenous pulmonary infection.