Kaneko Yukihiro, Yanagihara Katsunori, Miyazaki Yoshitsugu, Tsukamoto Kazuhiro, Hirakata Yoichi, Tomono Kazunori, Kadota Jun-ichi, Tashiro Takayoshi, Murata Ikuo, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan.
Antimicrob Agents Chemother. 2003 Dec;47(12):3694-8. doi: 10.1128/AAC.47.12.3694-3698.2003.
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 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.
我们在耐甲氧西林金黄色葡萄球菌（MRSA）和万古霉素不敏感金黄色葡萄球菌（VISA）引起的血源性肺部感染小鼠模型中，比较了新型喹诺酮类药物DQ - 113与万古霉素（VCM）和替考拉宁（TEIC）的效果。DQ - 113、VCM和TEIC对MRSA的最低抑菌浓度（MIC）分别为0.125、1.0和0.5微克/毫升；对VISA的MIC分别为0.25、8.0和8.0微克/毫升。用DQ - 113治疗导致MRSA感染模型中小鼠肺部活菌数量显著减少（用DQ - 113、VCM、TEIC治疗的小鼠及对照小鼠肺部细菌计数，分别为6.33±0.22、7.99±0.14、7.36±0.20和8.47±0.22 log10 CFU/肺[平均值±平均标准误差]，[与用VCM或TEIC治疗的组或未治疗组相比，用DQ - 113治疗的组P<0.01]）。感染VISA的小鼠先用环磷酰胺预处理，连续10天每天记录存活率。在此期间结束时，90%用DQ - 113治疗的小鼠仍存活，而其他三组中只有45%至55%的小鼠存活（与用VCM或TEIC治疗的组或未治疗组相比，用DQ - 113治疗的组P<0.05）。与其他三组小鼠肺部相比，DQ - 113也显著（P<0.05）减少了肺部活菌数量（用DQ - 113、VCM、TEIC治疗的小鼠及对照小鼠肺部细菌计数，分别为5.76±0.39、7.33±0.07、6.90±0.21和7.44±0.17 log10 CFU/肺）。组织病理学检查显示，与其他组小鼠相比，用DQ - 113治疗的小鼠炎症变化较轻。在所分析的抗生素中，DQ - 113的0至6小时浓度 - 时间曲线下面积（AUC(0 - 6)）/MIC参数以及AUC(0 - 6)超过MIC的时间最高。我们的结果表明，DQ - 113对治疗由MRSA和VISA菌株引起的血源性肺部感染有效且强效。
