Effects of DQ-113, a new quinolone, against methicillin- and vancomycin-resistant Staphylococcus aureus-caused hematogenous pulmonary infections in mice

Antimicrob Agents Chemother. 2003 Dec;47(12):3694-8. doi: 10.1128/AAC.47.12.3694-3698.2003.

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 0.5 microg/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0 microg/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 log10 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 log10 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.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / blood
  • Anti-Infective Agents / therapeutic use*
  • Blood-Borne Pathogens*
  • Injections, Intraperitoneal
  • Lung / metabolism
  • Lung / microbiology
  • Lung Diseases / drug therapy*
  • Lung Diseases / microbiology
  • Male
  • Methicillin Resistance*
  • Mice
  • Microbial Sensitivity Tests
  • Quinolones / administration & dosage
  • Quinolones / blood
  • Quinolones / therapeutic use*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects
  • Teicoplanin / therapeutic use
  • Vancomycin / therapeutic use
  • Vancomycin Resistance*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • DQ113
  • Quinolones
  • Teicoplanin
  • Vancomycin