喹诺酮类与β-内酰胺类/β-内酰胺酶抑制剂复方联合对嗜麦芽寡养单胞菌的抗菌活性

Activities of quinolones combined with β-lactam/β-lactamase inhibitors against Strenotrophomonas maltophilia

目的 了解嗜麦芽寡养单胞菌 (Strenotrophomonasmaltophilia)在延时培养时对喹诺酮类与 β 内酰胺 /酶抑制剂复方的MIC影响及联合应用抗菌活性。方法 微量肉汤稀释法测定MIC ,时间杀菌试验进行联合药敏试验并与棋盘法比较 ,并作耐药频率测定。结果 五种抗生素 48h测得MIC较 2 4h的MIC高 1～ 3倍 ;2 4h棋盘法测得头孢哌酮 /舒巴坦、替卡西林 /克拉维酸分别与左氧氟沙星、洛美沙星、环丙沙星联合用药对嗜麦芽寡养单胞菌的协同作用为 73 %～ 80 % ,48h则较 2 4h低 1 0 %～ 2 0 %。与时间杀菌试验测得的协同作用 50 %～ 66 %相近。联合用药的耐药频率明显低于单独用药。结论 48h判定MIC值可能更准确地反映嗜麦芽寡养单胞菌对抗生素的敏感性。时间杀菌试验较棋盘法更能真实反映出联合用药的效果。联合用药能减少细菌的耐药频率。

Objective To investigate the effect of an extended incubation of Strenotrophomonas maltophilia on the MIC of five antibiotics and the antibacterial activities of three quinolones combined with two β lactam/β lactamase inhibitors against Strenotrophomonas maltophilia . Methods Determining the MIC of antibiotics and the combination FIC indices of three quniolones with two β lactam/β lactamase inhibitors for 30 strains of Strenotrophomonas maltophilia by the broth dilution micromethod, time kill assay and checkerboard titration methods and detecting their resistant mutantation frequency. Results The MIC of five antibioics in 48 hours were higher 1～3 times than that in 24 hours. The synergy of checkerboard titration of cefoperazone/sulbactam or ticarcillin/clavulanic acid with levofloxacin, lomefloxacin, ciprofloxacin respectively for S.maltophilia in 24 hours were 70%～80% and that were higher 10%～20% than in 48 hours. The synergy of time kill assay was 50%～66%. The resistant mutantion frequency of combination was lower than that of single one. Conclusion Results of the MIC in 48 hours could correctly set their susceptibilities to antibiotics. Time kill assay was more discriminatory than checkerboard titration in demonstrating synergy for combinations. The combination of antibiotics could decrease the resistant mutantion frequency of S.maltophilia .