In vivo efficacy of a new quinolone, DQ-113, against Streptococcus pneumoniae in a mouse model.

Abstract

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 log10 CFU/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.

• Authors: Yoshiko Otsu, Katsunori Yanagihara, Yuichi Fukuda, 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. 3699-703 (Dec 2003) ISSN: 0066-4804 [Print] United States
• PMID: 14638468 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Infective Agents
• DQ113
• Fluoroquinolones
• Quinolones
• Ciprofloxacin
• Gatifloxacin

Topics

• Animals
• Anti-Infective Agents (blood, pharmacokinetics, therapeutic use)
• Ciprofloxacin (therapeutic use)
• Fluoroquinolones (therapeutic use)
• Gatifloxacin
• Lung (metabolism)
• Male
• Mice
• Mice, Inbred CBA
• Microbial Sensitivity Tests
• Penicillin Resistance
• Pneumonia, Pneumococcal (drug therapy, microbiology)
• Quinolones (blood, pharmacokinetics, therapeutic use)
• Survival Analysis