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Antimicrobial Agents and Chemotherapy, December 2003, p. 3694-3698, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3694-3698.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effects of DQ-113, a New Quinolone, against Methicillin- and Vancomycin-Resistant Staphylococcus aureus-Caused Hematogenous Pulmonary Infections in Mice

Yukihiro Kaneko,1 Katsunori Yanagihara,1,2* Yoshitsugu Miyazaki,1 Kazuhiro Tsukamoto,1,2 Yoichi Hirakata,1 Kazunori Tomono,1 Jun-ichi Kadota,1 Takayoshi Tashiro,1 Ikuo Murata,1,2 and Shigeru Kohno1,3

Second Department of Internal Medicine,1 Department of Pharmacotherapeutics,2 Division of Molecular & Clinical Microbiology, Department of Molecular Microbiology & Immunology, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan3

Received 16 July 2003/ Accepted 21 August 2003

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 µg/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0 µg/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 (AUC0-6)/MIC and the time that the AUC0-6 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.

* Corresponding author. Mailing address: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan. Phone: 81-95-849-7276. Fax: 81-95-849-7285. E-mail: kyana-ngs{at}umin.ac.jp.

Antimicrobial Agents and Chemotherapy, December 2003, p. 3694-3698, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3694-3698.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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