Effects of DQ-113, a new quinolone, against methicillin- and vancomycin-resistant Staphylococcus aureus-caused hematogenous pulmonary infections in mice.
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.
Kaneko
Yukihiro
Y
Second Department of Internal Medicine, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan.
Yanagihara
Katsunori
K
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; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D017848:Blood-Borne Pathogens; D007274:Injections, Intraperitoneal; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D017334:Teicoplanin / Q000627:therapeutic use; D014640:Vancomycin / Q000627:therapeutic use; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; C456082:DQ113; D015363:Quinolones; D017334:Teicoplanin; D014640:Vancomycin