Oz Yasemin, Akşit Filiz, Kiraz Nuri, Kiremitçi Abdurrahman
Eskişehir Osmangazi Universitesi Tip Fakültesi, Mikrobiyoloji Anabilim Dali, Eskişehir.
Mikrobiyol Bul. 2008 Jan;42(1):149-55.
The aim of this study was to investigate the in vitro interaction of amphotericin B in combination with fluconazole or voriconazole against Candida albicans clinical isolates by using a broth microdilution checkerboard assay and E-test. A total of 30 C. albicans strains isolated from blood, urine, sputum and pus samples were included to the study and the minimum inhibitory concentrations (MICs) of amphotericin B (AMB), fluconazole (FLU) and voriconazole (VOR) were determined by broth microdilution method and E-test. All strains tested for susceptibility were interpreted as susceptible by both methods (FLU MICs < 8 microg/ml, VOR and AMB MICs < 1 microg/ml). The rates of MIC agreement between two methods were as follows: AMB, 83%; FLU, 97%; VOR, 97%. AMB+ FLU and AMB+VOR combinations were tested by checkerboard broth microdilution and E-test methods. The combination test results were determined by using the fractional inhibitory concentration (FIC) index as synergistic, indifferent or antagonistic. AMB+FLU combination tested by checkerboard broth microdilution revealed synergy in one strain (3.3%) and antagonism in none, while the same combination tested by E-test revealed synergy in two (6.6%) and antagonism in four (13.3%) strains. The strains which exhibited synergy were different from eachother in two assays. This combination led to indifferent results in 23 (76.6%) of the strains. On the other hand AMB+VOR combination yielded synergistic results in two (6.6%) strains by both of the methods, however, these two strains were again different from eachother. No antagonism was detected by AMB+VOR combination while the combination was indifferent in 26 (86.6%) of the strains. Agreement between the checkerboard and E-test results was 87%. Although significant synergy was not detected in AMB+azole combinations, it was yet hopeful to obtain no antagonism. However, multi-center, large-scale, well standardized in-vitro and clinical studies about AMB and azole interaction which is a matter of debate, are necessary.
本研究的目的是通过肉汤微量稀释棋盘法和E试验，研究两性霉素B与氟康唑或伏立康唑联合应用对白色念珠菌临床分离株的体外相互作用。本研究共纳入了30株从血液、尿液、痰液和脓液样本中分离出的白色念珠菌菌株，并采用肉汤微量稀释法和E试验测定了两性霉素B（AMB）、氟康唑（FLU）和伏立康唑（VOR）的最低抑菌浓度（MIC）。两种方法检测的所有敏感菌株均被判定为敏感（FLU的MIC<8μg/ml，VOR和AMB的MIC<1μg/ml）。两种方法之间的MIC符合率如下：AMB为83%；FLU为97%；VOR为97%。通过棋盘肉汤微量稀释法和E试验方法检测AMB+FLU和AMB+VOR联合用药情况。联合试验结果通过分数抑菌浓度（FIC）指数确定为协同、无关或拮抗。棋盘肉汤微量稀释法检测AMB+FLU联合用药显示1株（3.3%）为协同作用，无拮抗作用；而E试验检测同一联合用药显示2株（6.6%）为协同作用，4株（13.3%）为拮抗作用。两种检测方法中表现出协同作用的菌株彼此不同。该联合用药在23株（76.6%）菌株中产生无关结果。另一方面，AMB+VOR联合用药在两种方法检测中均有2株（6.6%）菌株产生协同作用，然而，这两株菌株彼此也不同。AMB+VOR联合用药未检测到拮抗作用，该联合用药在26株（86.6%）菌株中为无关作用。棋盘法和E试验结果的符合率为87%。虽然在AMB+唑类联合用药中未检测到显著的协同作用，但未出现拮抗作用仍令人期待。然而，关于AMB与唑类相互作用这一有争议的问题，有必要进行多中心、大规模、标准化良好的体外和临床研究。
