Effects of DQ-113, a New Quinolone, against Methicillin- and Vancomycin-Resistant Staphylococcus aureus-Caused Hematogenous Pulmonary Infections in Mice
Effects of DQ-113, a New Quinolone, against Methicillin- and Vancomycin-Resistant Staphylococcus aureus-Caused Hematogenous Pulmonary Infections in Mice
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新喹诺酮类药物 DQ-113 对耐甲氧西林和万古霉素金黄色葡萄球菌引起的小鼠血源性肺部感染的作用
DOI：
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发表时间：
2003
影响因子：
4.9
通讯作者：
S. Kohno
中科院分区：
文献类型：
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作者：
Y. Kaneko;K. Yanagihara;Y. Miyazaki;K. Tsukamoto;Y. Hirakata;K. Tomono;J. Kadota;T. Tashiro;I. Murata;S. Kohno
摘要我们比较了新型喹诺酮类药物DQ-113、万古霉素（VCM）和替考拉宁（TEIC）对耐甲氧西林金黄色葡萄球菌（MRSA）和对VCM不敏感的金黄色葡萄球菌（MRSA）引起的小鼠血源性肺部感染的作用。金黄色葡萄球菌（VISA）。DQ-113、VCM和TEIC对MRSA的MIC分别为0.125、1.0和0.5μ g/ml;对VISA的MIC分别为0.25、8.0和8.0μ g/ml。用DQ-113治疗导致MRSA感染模型中使用的小鼠肺中活菌数量的显著减少（用DQ-113、VCM和TEIC处理的小鼠和对照小鼠的计数分别为6.33 ± 0.22、7.99± 0.14、7.36 ± 0.20、7.36 ± 0.20、7.38 ± 0.22、7.99± 0.14、7.36 ± 0.20、7.99 ± 0.14）。和8.47 ± 0.22 log 10 CFU/肺[平均值±平均值的标准误差][DQ-113治疗组与VCM或TEIC治疗组或未治疗组相比P < 0.01]）。用环磷酰胺预处理感染VISA的小鼠，每天记录存活率，持续10天。在该时期结束时，90%的DQ-113处理的小鼠仍然存活，而其他三个组中仅45至55%的小鼠仍然存活（与用VCM或TEIC处理的组或未处理组相比，用DQ-113处理的组的P < 0.05）。DQ-113还显著（P < 0.05）减少了肺中的活菌数（与其他三组的肺中的活菌数相比，用DQ-113、VCM和TEIC处理的小鼠和对照小鼠的计数分别为5.76 ± 0.39、7.33 ± 0.07、6.90± 0.21和7.44 ± 0.17 log 10 CFU/肺）。组织学检查显示DQ-113治疗组小鼠的炎症变化比其他组小鼠的炎症变化轻。在分析的抗生素中，DQ-113的0 - 6 h浓度-时间（AUC 0 -6）/MIC和AUC 0 -6超过MIC的时间参数最高。我们的研究结果表明，DQ-113是强效和有效的治疗由MRSA和VISA菌株引起的血源性肺部感染。
ABSTRACT 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 0.5μ g/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0μ g/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 (AUC0-6)/MIC and the time that the AUC0-6 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.