Gould I M, Milne K
Department of Medical Microbiology, Aberdeen Royal Hospital NHS Trust, Aberdeen Royal Infirmary, UK.
J Antimicrob Chemother. 1997 Jan;39(1):53-61. doi: 10.1093/jac/39.1.53.
Six isolates each of Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Citrobacter spp., Serratia spp., Acinetobacter spp. and Enterobacter spp. (total 60 strains) were studied against the combination of piperacillin/tazobactam plus gentamicin or ciprofloxacin at physiological concentrations by the microtitre chequerboard method incorporating simultaneous time-kill curves. Tazobactam was fixed at 4 mg/L. Gentamicin plus piperacillin/tazobactam was a synergic combination against 28 strains at 2 h, 51 at 5 h and 54 at 24 h as assessed by time-kill curves and synergic or additive (FBC index < or = 1) against all 60 strains at 24 h by chequerboards. The corresponding figures for ciprofloxacin plus piperacillin/tazobactam were seven, 26, 52 and 58 respectively. Antagonism (FBC index > or = 4) was demonstrated for one strain to each combination at 24 h. There were no significant differences between FIC indices and FBC indices for each antibiotic combination. Gentamicin plus piperacillin/tazobactam gave > or = 3 log kill for 47 strains by 2 h, 56 by 5 h and 59 by 24 h. Ciprofloxacin plus piperacillin/tazobactam gave > or = 3 log kill for 22 strains by 2 h, 36 by 5 h and 56 by 24 h. In conclusion both antibiotic combinations at physiological concentrations were synergic or additive at 24 h for the majority of strains tested although notably gentamicin plus piperacillin/tazobactam gave faster kill. Antagonism was rarely seen. Both combinations are likely to prove beneficial for treatment of serious infections.
采用微量滴定棋盘法并结合同步时间杀菌曲线，研究了粪肠球菌、金黄色葡萄球菌、表皮葡萄球菌、化脓性链球菌、嗜麦芽窄食单胞菌、铜绿假单胞菌、柠檬酸杆菌属、沙雷菌属、不动杆菌属和肠杆菌属的6株分离菌（共60株）对生理浓度的哌拉西林/他唑巴坦联合庆大霉素或环丙沙星的敏感性。他唑巴坦固定在4mg/L。根据时间杀菌曲线评估，庆大霉素加哌拉西林/他唑巴坦在2小时时对28株菌有协同作用，5小时时对51株菌有协同作用，24小时时对54株菌有协同作用；根据棋盘法评估，在24小时时对所有60株菌有协同或相加作用（FBC指数≤1）。环丙沙星加哌拉西林/他唑巴坦的相应数字分别为7、26、52和58。在24小时时，每种联合用药对1株菌表现出拮抗作用（FBC指数≥4）。每种抗生素联合用药的FIC指数和FBC指数之间没有显著差异。庆大霉素加哌拉西林/他唑巴坦在2小时时对47株菌有≥3个对数级的杀菌作用，5小时时对56株菌有≥3个对数级的杀菌作用，24小时时对59株菌有≥3个对数级的杀菌作用。环丙沙星加哌拉西林/他唑巴坦在2小时时对22株菌有≥3个对数级的杀菌作用，5小时时对36株菌有≥3个对数级的杀菌作用，24小时时对56株菌有≥3个对数级 的杀菌作用。总之，对于大多数测试菌株，两种抗生素联合用药在生理浓度下在24小时时具有协同或相加作用，尽管值得注意的是庆大霉素加哌拉西林/他唑巴坦杀菌速度更快。很少见到拮抗作用。两种联合用药可能对严重感染的治疗有益。
