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Antimicrobial Agents and Chemotherapy, December 2003, p. 3699-3703, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3699-3703.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vivo Efficacy of a New Quinolone, DQ-113, against Streptococcus pneumoniae in a Mouse Model

Yoshiko Otsu,1 Katsunori Yanagihara,1,2* Yuichi Fukuda,1 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, Nagasaki University School of Medicine,1 Department of Pharmacotherapeutics, Nagasaki University Graduate School of Pharmaceutical Sciences,2 Department of Molecular Microbiology and Immunology, Division of Molecular and Clinical Microbiology, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan3

Received 30 May 2003/ Returned for modification 3 July 2003/ Accepted 31 August 2003

DQ-113 is a new quinolone with potent activity against gram-positive pathogens. The in vivo activity of DQ-113 against Streptococcus pneumoniae was compared with those of gatifloxacin and ciprofloxacin in a mouse model. For this purpose, two strains of S. pneumoniae were used: penicillin-susceptible S. pneumoniae (PSSP) and penicillin-resistant S. pneumoniae (PRSP). The survival rates of mice infected with PSSP and PRSP at 14 days after infection were 80% in the DQ-113-treated group and 0 to 10% in the other three groups. In murine infections caused by PSSP, the 50% effective doses (ED50s) of DQ-113, gatifloxacin, and ciprofloxacin were 6.0, 41.3, and 131.6 mg/kg, respectively. Against PRSP-caused pneumonia in mice, the ED50s of DQ-113, gatifloxacin, and ciprofloxacin were 7.6, 64.7, and 125.9 mg/kg, respectively. Compared with the other drugs, DQ-113 showed excellent therapeutic efficacy and eradicated viable bacteria in both PSSP- and PRSP-infected mice. The means ± standard errors of the means of viable bacterium counts in the lungs of gatifloxacin-treated, ciprofloxacin-treated, and untreated control mice infected with PSSP were 2.91 ± 0.34, 3.13 ± 0.48, and 3.86 ± 0.80 log10CFU/ml, respectively. The same counts in mice infected with PRSP treated with the same three agents were 6.57 ± 0.99, 6.54 ± 0.40, and 7.17 ± 0.43 log10 CFU/ml, respectively. DQ-113 significantly decreased the number of viable bacteria in the lungs compared with gatifloxacin and ciprofloxacin. Of the drugs analyzed, the pharmacokinetic-pharmacodynamic parameter of area under the concentration-time curve (AUC)/MIC ratio for DQ-113 was significantly higher than those for gatifloxacin and ciprofloxacin. Our results suggest that DQ-113 has potent in vivo efficacy against both PSSP and PRSP.

* 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. 3699-3703, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3699-3703.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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