Visalli M A, Bajaksouzian S, Jacobs M R, Appelbaum P C
Department of Pathology (Clinical Microbiology), Hershey Medical Center, Pennsylvania 17033, USA.
Antimicrob Agents Chemother. 1997 Jul;41(7):1475-81. doi: 10.1128/AAC.41.7.1475.
In the first part of this study, agar dilution MICs were used to test the activities of trovafloxacin, ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin, clinafloxacin, ceftazidime, and imipenem against 458 gram-negative nonfermenters. The overall respective MICs at which 50% of isolates are inhibited (MIC50s) and MIC90s were as follows: trovafloxacin, 1.0 and 16.0 microg/ml; ciprofloxacin, 2.0 and 16.0 microg/ml; ofloxacin, 2.0 and 32.0 microg/ml; levofloxacin, 1.0 and 16.0 microg/ml; sparfloxacin, 1.0 and 16.0 microg/ml; clinafloxacin, 0.5 and 4.0 microg/ml; ceftazidime, 8.0 and 128.0 microg/ml; imipenem, 2.0 and 256.0 microg/ml. Clinafloxacin was the most active of all the quinolones tested. The MIC90s of trovafloxacin were < or = 4.0 microg/ml for Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Flavobacterium odoratum, and Chryseobacterium meningosepticum; trovafloxacin MIC90s were < or = 2.0 microg/ml for Moraxella spp., Pseudomonas stutzeri, and Chryseobacterium indologenes-C. gleum. Of the other quinolones tested, the MICs of sparfloxacin and levofloxacin were lower than those of ciprofloxacin and ofloxacin. High ceftazidime MICs (> or = 32.0 microg/ml) were observed for all nonfermentative species tested. Although for the majority of strains tested imipenem MICs were < or = 8.0 microg/ml, high imipenem MICs were observed for many species, especially S. maltophilia, Burkholderia cepacia, F. odoratum, and Chryseobacterium meningosepticum. For Alcaligenes xylosoxidans strains, the MICs of all compounds were generally a few dilutions lower than those for Alcaligenes faecalis-A. odorans. Time-kill studies with five strains revealed that trovafloxacin and all quinolones yielded more rapid time-kill kinetics than ceftazidime and imipenem. Synergy testing by checkerboard titrations of 286 strains with trovafloxacin combined with ceftazidime, amikacin, and imipenem revealed fractional inhibitory concentration (FIC) indices in the range indicating synergism (< or = 0.5) for 81, 41, and 40 strains, respectively, and FIC indices indicating additivity or indifference (> 0.5 to 4.0) for 205, 245, and 246 strains, respectively. No FIC indices indicating antagonism (> 4.0) were observed. Synergy between trovafloxacin and ceftazidime was found for 32 of 36 S. maltophilia strains. Time-kill studies with 20 strains showed that for most strains for which FIC indices were in the range indicating additivity or indifference, FIC indices indicated synergy by the time-kill method. Synergy was particularly noticeable for S. maltophilia strains with combinations of ceftazidime and trovafloxacin.
在本研究的第一部分，采用琼脂稀释法测定了曲伐沙星、环丙沙星、氧氟沙星、左氧氟沙星、司帕沙星、克林沙星、头孢他啶和亚胺培南对458株革兰阴性非发酵菌的活性。50%的分离株被抑制时的总体MIC50及MIC90如下：曲伐沙星，1.0和16.0μg/ml；环丙沙星，2.0和16.0μg/ml；氧氟沙星，2.0和32.0μg/ml；左氧氟沙星，1.0和16.0μg/ml；司帕沙星，1.0和16.0μg/ml；克林沙星，0.5和4.0μg/ml；头孢他啶，8.0和128.0μg/ml；亚胺培南，2.0和256.0μg/ml。克林沙星是所有受试喹诺酮类药物中活性最强的。对于铜绿假单胞菌、嗜麦芽窄食单胞菌、芳香黄杆菌和脑膜炎败血金黄杆菌，曲伐沙星的MIC90≤4.0μg/ml；对于莫拉菌属、斯氏假单胞菌和产吲哚金黄杆菌-格氏金黄杆菌，曲伐沙星的MIC90≤2.0μg/ml。在其他受试喹诺酮类药物中，司帕沙星和左氧氟沙星的MIC低于环丙沙星和氧氟沙星。对所有受试非发酵菌均观察到较高的头孢他啶MIC（≥32.0μg/ml）。虽然大多数受试菌株的亚胺培南MIC≤8.0μg/ml，但对许多菌种，尤其是嗜麦芽窄食单胞菌、洋葱伯克霍尔德菌、芳香黄杆菌和脑膜炎败血金黄杆菌，观察到较高的亚胺培南MIC。对于木糖氧化产碱杆菌菌株，所有化合物的MIC通常比对粪产碱杆菌-奥氏产碱杆菌低几个稀释度。对5株菌进行的时间杀菌研究表明，曲伐沙星和所有喹诺酮类药物比头孢他啶和亚胺培南产生更快的杀菌动力学。用棋盘滴定法对286株菌进行曲伐沙星与头孢他啶、阿米卡星和亚胺培南的协同试验，结果显示分别有81、41和40株菌的部分抑菌浓度（FIC）指数在协同范围（≤0.5）内，分别有205、245和246株菌的FIC指数表明为相加作用或无作用（＞0.5至4.0）。未观察到表明拮抗作用（＞4.0）的FIC指数。在36株嗜麦芽窄食单胞菌中，发现32株曲伐沙星与头孢他啶之间有协同作用。对20株菌进行的时间杀菌研究表明，对于大多数FIC指数在相加作用或无作用范围内的菌株，FIC指数通过时间杀菌法表明为协同作用。头孢他啶与曲伐沙星联合应用时，嗜麦芽窄食单胞菌菌株的协同作用尤为明显。
