抗生素對抗methicillin 金黃色葡萄球菌之混合效應研究

Abstract

毒理學上曾針對有機物之混合毒性加以研究，依照有機物的致毒機制根據有機毒物之致毒機制及劑量-反應曲線之斜率加以分類，並對混合效應歸納出五個重要預測準則。對反應性之有機物歸納出其產生協同作用(synergism)的主要條件;包括作用機制必須不同，斜率必須相當小等等。 1961年對methicillin抗藥性的金黃色葡萄球菌(MRSA)首次被發現後，MRSA已成為院內感常見病原菌。因此本研究以MRSA為試驗物種，選擇29種抗生素，並將依其作用機制加以分類，進行一連串的混合效應試驗。觀察其對MRSA的抑制情形，探討混合效應模式的預測方法，並與過去研究加以比較，其預測準則之可行性。 毒理學與藥理學之間有相當之共同性，例如藥物對致病菌而言就是一種毒性物質，如本研究能有效地預測混合效應則在藥理學上亦有應用價值。本研究將以探討兩抗生素混合產生協同作用之療效為目的。 本研究結果顯示，兩抗生素小斜率不同作用機制下的混合類別，其產生混合效應為協同作用（Synergism）的機率較高，產生的比例達75％。同時分別以混濁度法、平板法、Time-Kill curve 與Multox Model 四種不同的試驗方法進行抗生素之混合效應試驗。結果均與毒理學劑量-反應模式所得的結果具有相當的一致性，這亦與過去預測模式結果相同。因此可證明劑量-反應曲線模式對抗生素混合使用的療效預測具有其可行性及價值。

During the past few years, an investigation was developed to study the toxicity of organic toxicants. The study was found, when toxicants have a small slope tend to act synergistically while have a large slope may produce antagonistic effect. From the results of this study, it was found that synergism was likely to be observed when the combination of antibiotics which were different mechanism and small dose-response curve slopes. Methicillin- resistant Staphylococcus aures (MRSA) is an important case of hospital and community acquired infection. The research used Methicillin- resistant Staphylococcus aures (MRSA) as test organism. The possibility of predicting the combined effects of mixtures of antibiotics. Comparison can then be made with our previous results. From the results of the study, we were found that synergism was produced with the combination of antibiotics which were different mechanism and small dose-response curve slopes. Comparison with four different method, turbidity method, agar plate test, multox model and time-kill curve study were preferred to use in defining the effects of antibiotics combination in treatment, we also can get most the same result. This shows that the parameter of dose-response curve is good at application on predicting the combined therapeutic effects of mixtures of antibiotics.