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

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.

• Authors: Yukihiro Kaneko, Katsunori Yanagihara, Yoshitsugu Miyazaki, Kazuhiro Tsukamoto, Yoichi Hirakata, Kazunori Tomono, Jun-ichi Kadota, Takayoshi Tashiro, Ikuo Murata, Shigeru Kohno
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 47 Issue 12 Pg. 3694-8 (Dec 2003) ISSN: 0066-4804 [Print] United States
• PMID: 14638467 (Publication Type: Journal Article)

Chemical References

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

Topics

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