Murillo Oscar, Pachón M Eugenia, Euba Gorane, Verdaguer Ricard, Tubau Fe, Cabellos Carmen, Cabo Javier, Gudiol Francesc, Ariza Javier
Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona, Spain.
J Infect. 2009 Mar;58(3):220-6. doi: 10.1016/j.jinf.2009.01.005. Epub 2009 Feb 12.
Since levofloxacin at high doses was the best therapy in staphylococcal tissue-cage model of foreign-body infection, we hypothesized that moxifloxacin with higher ratio of area under the concentration-time curve to the MIC (AUC/MIC) would provide better results.
MICs, MBCs, MPCs (mutant prevention concentration) and 24h kill-curves were determined in the log and stationary phases. Using the aforementioned model, we tested the efficacy of levofloxacin 100mg/kg/d, moxifloxacin 40mg/kg/d and moxifloxacin 80mg/kg/d; they were equivalent to human levels for 1000mg/d, 400mg/d and 800mg/d, respectively. We screened for the appearance of resistant strains.
MICs and MBCs in logarithmic and stationary phases and MPCs of levofloxacin were 0.5, 1 and 4, 0.8microg/ml, respectively, and those of moxifloxacin 0.12, 0.25 and 2, 0.25microg/ml. AUC/MIC were 234 (levofloxacin), 431 (moxifloxacin 40) and 568 (moxifloxacin 80). Bacterial counts decreases in tissue-cage fluids (means of logCFU/ml) were -1.81 (n=25), -1.31 (23), and -1.46 (20), respectively; for controls it was 0.24 (22). All groups were better than controls (p<0.05); no differences between them existed.
Moxifloxacin with higher AUC/MIC ratio did not improve the efficacy of high doses of levofloxacin.
由于高剂量左氧氟沙星在葡萄球菌异物感染组织笼模型中是最佳治疗方法，我们推测曲线下面积与最低抑菌浓度之比（AUC/MIC）更高的莫西沙星会产生更好的效果。
测定对数期和稳定期的最低抑菌浓度（MIC）、最低杀菌浓度（MBC）、突变预防浓度（MPC）以及24小时杀菌曲线。使用上述模型，我们测试了100mg/kg/d左氧氟沙星、40mg/kg/d莫西沙星和80mg/kg/d莫西沙星的疗效；它们分别相当于人类每日1000mg、400mg和800mg的剂量水平。我们筛选耐药菌株的出现情况。
左氧氟沙星在对数期和稳定期的MIC、MBC以及MPC分别为0.5、1和4、0.8μg/ml，莫西沙星的分别为0.12、0.25和2、0.25μg/ml。AUC/MIC分别为234（左氧氟沙星）、431（40mg/kg/d莫西沙星）和568（80mg/kg/d莫西沙星）。组织笼液中的细菌计数减少（logCFU/ml平均值）分别为-1.81（n=25）、-1.31（23）和-1.46（20）；对照组为0.24（22）。所有组均优于对照组（p<0.05）；它们之间无差异。
AUC/MIC比值更高的莫西沙星并未提高高剂量左氧氟沙星的疗效。
