Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, United Kingdom.
Antimicrob Agents Chemother. 2012 Jun;56(6):3080-5. doi: 10.1128/AAC.05870-11. Epub 2012 Apr 9.
The treatment of Gram-negative infections is increasingly compromised by the spread of resistance. With few agents currently in development, clinicians are now considering the use of unorthodox combination therapies for multidrug-resistant strains. Here we assessed the in vitro activity of the novel lipoglycopeptide telavancin (TLV) when combined with colistin (COL) versus 13 Gram-negative type strains and 66 clinical isolates. Marked synergy was observed in either checkerboard (fractional inhibitory concentration index [FICI], <0.5; susceptibility breakpoint index [SBPI], >2) or time-kill assays (>2-log reduction in viable counts compared with starting inocula at 24 h) versus the majority of COL-susceptible enterobacteria, Stenotrophomonas maltophilia, and Acinetobacter baumannii isolates, but only limited effects were seen against Pseudomonas aeruginosa or strains with COL resistance. Using an Etest/agar dilution method, the activity of TLV was potentiated by relatively low concentrations of COL (0.25 to 0.75 μg/ml), reducing the MIC of TLV from >32 μg/ml to ≤ 1 μg/ml for 35% of the clinical isolates. This provides further evidence that glycopeptide-polymyxin combinations may be a useful therapeutic option in the treatment of Gram-negative infections.
革兰氏阴性感染的治疗因耐药性的传播而日益受到影响。由于目前开发的药物很少，临床医生现在正在考虑使用非传统的联合治疗方法来治疗多药耐药菌株。在这里，我们评估了新型糖肽类药物替拉万星（TLV）与多粘菌素（COL）联合使用时对 13 种革兰氏阴性标准菌株和 66 种临床分离株的体外活性。无论是棋盘微量稀释法（FICI＜0.5；SBPI＞2）还是时间杀伤试验（与起始接种物相比，24 小时后活菌计数减少＞2 对数级）都观察到了明显的协同作用，对大多数 COL 敏感的肠杆菌、嗜麦芽窄食单胞菌和鲍曼不动杆菌分离株，但对铜绿假单胞菌或对 COL 耐药的菌株仅显示出有限的作用。使用 Etest/琼脂稀释法，COL 的浓度（0.25 至 0.75μg/ml）较低时可增强 TLV 的活性，使 35%的临床分离株的 TLV MIC 从＞32μg/ml 降低至≤1μg/ml。这进一步证明了糖肽类-多粘菌素联合治疗可能是治疗革兰氏阴性感染的一种有效治疗选择。
