Effects ofDQ-113, a New Quinolone, against Methicillin- and Vancomycin-Resistant Staphylococcus aureus -Caused Hematogenous PulmonaryInfections inMice

Abstract

ABSTRACT We compared the effects of DQ-113, a new quinolone, to those of vancomycin (VCM) and teicoplanin (TEIC) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA). The MICs of DQ-113, VCM, and TEIC for MRSA were 0.125, 1.0, and 0.5μ g/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0μ g/ml, respectively. Treatment with DQ-113 resulted in a significant decrease in the number of viable bacteria in the lungs of the mice used in the MRSA infection model (counts in mice treated with DQ-113, VCM, and TEIC and control mice, 6.33 ± 0.22, 7.99± 0.14, 7.36 ± 0.20, and 8.47 ± 0.22 log 10 CFU/lung [mean ± standard error of the mean], respectively [ P < 0.01 for the group treated with DQ-113 compared with the group treated with VCM or TEIC or the untreated group]). Mice infected with VISA were pretreated with cyclophosphamide, and the survival rate was recorded daily for 10 days. At the end of this period, 90% of the DQ-113-treated mice were still alive, whereas only 45 to 55% of the mice in the other three groups were still alive ( P < 0.05 for the group treated with DQ-113 compared with the group treated with VCM or TEIC or the untreated group]). DQ-113 also significantly ( P < 0.05) reduced the number of viable bacteria in the lungs compared with those in the lungs of the other three groups (counts in mice treated with DQ-113, VCM, and TEIC and control mice, 5.76 ± 0.39, 7.33 ± 0.07, 6.90± 0.21, and 7.44 ± 0.17 log 10 CFU/lung, respectively). Histopathological examination revealed milder inflammatory changes in DQ-113-treated mice than in the mice in the other groups. Of the antibiotics analyzed, the parameters of area under the concentration-time from 0 to 6 h (AUC 0-6 )/MIC and the time that the AUC 0-6 exceeded the MIC were the highest for DQ-113. Our results suggest that DQ-113 is potent and effective for the treatment of hematogenous pulmonary infections caused by MRSA and VISA strains.