Visalli M A, Jacobs M R, Appelbaum P C
Department of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Antimicrob Agents Chemother. 1998 Aug;42(8):2002-5. doi: 10.1128/AAC.42.8.2002.
The present study examined the activities of trovafloxacin, levofloxacin, and ciprofloxacin, alone and in combination with cefoperazone, ceftazidime, cefpirome, and gentamicin, against 100 strains of Stenotrophomonas maltophilia by the MIC determination method and by synergy testing of the combinations by the time-kill and checkerboard titration methods for 20 strains. The respective MICs at which 50% and 90% of isolates were inhibited for the drugs used alone were as follows: trovafloxacin, 0.5 and 2.0 microg/ml; levofloxacin, 2.0 and 4.0 microg/ml; ciprofloxacin, 4.0 and 16.0 microg/ml; cefoperazone, >128.0 and >128.0 microg/ml; ceftazidime, 32.0 and >128.0 microg/ml; cefpirome, >128.0 and >128.0 microg/ml; and gentamicin, 128.0 and >128.0 microg/ml. Synergistic fractional inhibitory concentration indices (</=0.5) were found for >/=50% of strains for trovafloxacin-cefoperazone, trovafloxacin-ceftazidime, levofloxacin-cefoperazone, levofloxacin-ceftazidime, ciprofloxacin-cefoperazone, and ciprofloxacin-ceftazidime, with other combinations affecting fewer strains. For 20 strains tested by the checkerboard titration and time-kill methods, synergy (>/=100-fold drop in count compared to the count achieved with the more active compound) was more pronounced after 12 h due to regrowth after 24 h. At 12 h, trovafloxacin at 0.004 to 0.5 microg/ml showed synergy with cefoperazone for 90% of strains, with ceftazidime for 95% of strains with cefpirome for 95% of strains, and with gentamicin for 65% of strains. Levofloxacin at 0.03 to 0.5 microg/ml and ciprofloxacin at 0.5 to 2.0 microg/ml showed synergy with cefoperazone for 80% of strains, with ceftazidime for 90 and 85% of strains, respectively, with cefpirome for 85 and 75% of strains, respectively, and with gentamicin for 65 and 75% of strains, respectively. Time-kill assays were more discriminatory than checkerboard titration assays in demonstrating synergy for all combinations.
本研究采用微量肉汤稀释法测定了曲伐沙星、左氧氟沙星和环丙沙星单独使用时以及与头孢哌酮、头孢他啶、头孢匹罗和庆大霉素联合使用时对100株嗜麦芽窄食单胞菌的活性,并通过时间杀菌法和棋盘滴定法对20株菌进行联合用药的协同性检测。单独使用各药物时,抑制50%和90%分离菌株的相应最低抑菌浓度(MIC)如下:曲伐沙星,0.5和2.0μg/ml;左氧氟沙星,2.0和4.0μg/ml;环丙沙星,4.0和16.0μg/ml;头孢哌酮,>128.0和>128.0μg/ml;头孢他啶,32.0和>128.0μg/ml;头孢匹罗,>128.0和>128.0μg/ml;庆大霉素,128.0和>128.0μg/ml。曲伐沙星 - 头孢哌酮、曲伐沙星 - 头孢他啶、左氧氟沙星 - 头孢哌酮、左氧氟沙星 - 头孢他啶、环丙沙星 - 头孢哌酮和环丙沙星 - 头孢他啶对≥50%的菌株呈现协同性分数抑菌浓度指数(≤0.5),其他联合用药影响的菌株较少。对于通过棋盘滴定法和时间杀菌法检测的20株菌,由于24小时后出现再生长,12小时时协同作用(与活性更强的化合物相比,菌数下降≥100倍)更为明显。在12小时时,0.004至0.5μg/ml的曲伐沙星与头孢哌酮对90%的菌株、与头孢他啶对95%的菌株、与头孢匹罗对95%的菌株以及与庆大霉素对65%的菌株呈现协同作用。0.03至0.5μg/ml的左氧氟沙星和0.5至2.0μg/ml的环丙沙星与头孢哌酮分别对80%的菌株、与头孢他啶分别对90%和85%的菌株、与头孢匹罗分别对85%和75%的菌株以及与庆大霉素分别对65%和75%的菌株呈现协同作用。在证明所有联合用药的协同作用方面,时间杀菌试验比棋盘滴定试验更具鉴别力。