抗生素對大腸桿菌之混合毒性效應研究

Abstract

過去，曾以大腸杆菌和螢光菌為實驗物種，針對有機毒物之混合毒性進行研究，依有機毒物之致毒機制以及劑量－反應曲線的斜率作為主要的分類工具，對於混合疚之協力效應（joint action）歸納出五個重要之預測準則。 本研究主要是以大腸杆菌為試驗物種，選擇若干種抗生素，依其對細菌抑制作用的機制將之分類，利用分類後的結果，進行一系列混合毒性試驗，觀察其對大腸杆菌之生長制情形，探討混合毒性模式之預測方法，並與過去所得的結果及準則相比較，是否不同物種、不同毒性物質間，其預測準則之可應用性。 由於毒理學與藥理學之相似性，如本研究之成果能有效地預測混合效應之模式，在藥理學上將能應用於控制病菌感染，在現今醫學界普遍面臨致病菌具高抗藥性，以致多數抗生素無法有效抑制病菌繁殖，本研究之主要目的為以兩種抗生素混合，使其產生協同作用（synergism）之療效。 本研究之實驗結果顯示，由兩個作用機制不同、且其劑量－反應曲線斜率小的抗生素混合併用下，產生協同作用（synergism）的機率最大，可達78.6%。同時以平板法和Time-Kill curve兩種不同試驗方法，不同參數判定抗生素的混合併用效應上，均與以毒理學劑量－瓜模式所得到的結果比較方面，有相當的一致性存在，這也與過去研究所得到的預測模式相同，證明以劑量反應參數來對抗生素的混合併用療效預測上，有其可行性與價值，值得進一步作深入的探討。

During the past few years, an investigation was developed to study the toxicity of organic toxicants with E. coli and P. phosphorium. We have derived five prediction criteria for estimating the joint toxic effects of organic mixtures. In the proposed research, we investigated the possibility of predicting the combined therapeutic effects of mixtures of antibiotics. Based on the mechanism of various antibiotics and their individual dose-response curves, we expect to derive a series of prediction criteria for the combined therapeutic effects. Comparison can then be made with our previous results. From the results of this study, it was found that synergism was more likely to be observed when dealing with the combinations of antibiotics which were different mechanisms and of small dose-response curve slopes. No synergy observed in other types of combinations. Comparison with two different methods, agar plate test and time-kill curve study which were preferred to use in defining the effects of antibiotics combination in chemotherapy, we also can get most the same results. This shows that the parameters of dose-response curve is good at applicaton on predicting the combined therapeutic effects of mixtures of antibiotics.