In vivo efficacy of a new quinolone, DQ-113, against Streptococcus pneumoniae in a mouse model.
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.
Otsu
Yoshiko
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Yanagihara
Katsunori
K
Fukuda
Yuichi
Y
Miyazaki
Yoshitsugu
Y
Tsukamoto
Kazuhiro
K
Hirakata
Yoichi
Y
Tomono
Kazunori
K
Kadota
Jun-ichi
J
Tashiro
Takayoshi
T
Murata
Ikuo
I
Kohno
Shigeru
S
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000627:therapeutic use; D000077734:Gatifloxacin; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016019:Survival Analysis
D000890:Anti-Infective Agents; C456082:DQ113; D024841:Fluoroquinolones; D015363:Quinolones; D002939:Ciprofloxacin; D000077734:Gatifloxacin