抗生素混合效應在最小殺菌濃度之表現

Abstract

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。本研究將以探討兩抗生素混合效應在最小殺菌濃度之表現為目的。 1961年對methicillin抗藥性的金黃色葡萄球菌(MRSA)首次被發現後，MRSA已成為院內感染常見病源菌。因此本研究以MRSA為試驗物種，選擇9種抗生素，依其作用機制加以分類，進行一連串的混合效應試驗。觀察混合效應對MRSA的最小殺菌濃度（MBC）變化情形，探討MBC在混合效應模式的表現，並與Mtox 7 model加以分析比較，找出彼此的相關性。 本研究結果顯示，混合效應使MRSA的MBC下降4倍以上的類別，以Vancomycin–Gentamicin的機率較高，達87.5﹪，且大斜率抑制細胞壁合成和大斜率抑制蛋白質合成的混合類別，產生MBC下降4倍或以上的機率較高，有61.11﹪。利用Mtox7 Model分析比較，發現兩抗生素之間的混合效應模式為Response addition（RA），即λ=0、r = -1，可造成協同殺菌作用。

Infections due to Methicillin- resistant Staphylococcus aures (MRSA) continued to be a significant problem in the 1990s. Clinicians now have to face the emergence of strains with reduced susceptibility to vancomycin, i.e., so-called glycopeptide-intermediate Staphylococcus aures (GISA). Therefore, there is a clearly a need for new antibiotic regimens with strong early bactericidal activity against MRSA. In this field, an alternative to the development of new classes of agents could be the use of combinations of well-known compounds. The aim of our study was to investigate the effect on MBC of different combination between disruption of cell wall biosynthesis antibiotics and inhibition protein biosynthesis antibiotics against clinical MRSA strains. Furthermore, to discuss the synergistic bactericidal effect with Mtox7 model. From the results of the study, the probability of combination to enormously reduce MBC for Vancomycin–Gentamicin were 87.5﹪ and combination between large slope disruption of cell wall biosynthesis antibiotics and large slope inhibition protein biosynthesis antibiotic were 61.11﹪that could enormously reduce MBC. Comparison with Mtox7 model, the relationship of synergistic bactericidal effect was response addition（RA）.