Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
J Antibiot (Tokyo). 2013 Dec;66(12):705-8. doi: 10.1038/ja.2013.84. Epub 2013 Aug 28.
The lack of active antimicrobial agents against multidrug-resistant (MDR) Acinetobacter baumannii has posed great threat to the public health. Combination therapies with antibiotics owning different antimicrobial mechanisms have been proposed as good options for treating MDR A. baumannii infections. This study was aimed to investigate the in vitro effects of tigecycline in combination with colistin and sulbactam against MDR A. baumannii. A total of 70 strains from two hospitals in China were examined in the study. The checkerboard method was used for determining synergistic activity of different antibiotic combinations. Tigecycline/colistin combination displayed synergistic and partial synergistic activity in 24.3% of the isolates, whereas the tigecycline/sulbactam combination showed synergistic and partial synergistic activity in 64.3% of the isolates. Neither of the combinations showed antagonism in this study. In addition, for evaluating the ability of combinations on resistance prevention, mutant prevention concentrations (MPCs) of tigecycline, colistin, sulbactam alone and tigecycline in combination with colistin and sulbactam were studied against MDR A. baumannii. Compared with tigecycline used alone, combination therapies could achieve lower MPCs of tigecycline. However, when the MPCs of dual-drug therapy were in conjunction with clinical pharmacokinetic profiles, combinations may not strictly curb the occurrence of resistance at current dosage regimen. In summary, this study suggested that combination therapy was a good option for treating MDR A. baumannii infections. But the finding that combination with these drugs at current dosage regimen may not prevent emergence of resistance warranted further studies on dosage of combined antibiotics required for achieving resistance prevention.
针对多重耐药（MDR）鲍曼不动杆菌缺乏有效的抗菌药物，这对公众健康构成了巨大威胁。具有不同抗菌机制的抗生素联合治疗已被提议作为治疗 MDR A. baumannii 感染的良好选择。本研究旨在研究替加环素联合多粘菌素和舒巴坦对 MDR A. baumannii 的体外作用。本研究共检测了来自中国两家医院的 70 株菌。棋盘法用于确定不同抗生素组合的协同作用。替加环素/多粘菌素联合在 24.3%的分离物中显示协同和部分协同作用，而替加环素/舒巴坦联合在 64.3%的分离物中显示协同和部分协同作用。在本研究中，两种组合均未显示拮抗作用。此外，为了评估组合对耐药预防的能力，研究了替加环素、多粘菌素、舒巴坦单独以及替加环素与多粘菌素和舒巴坦联合对 MDR A. baumannii 的突变预防浓度（MPC）。与单独使用替加环素相比，联合治疗可以降低替加环素的 MPC。然而，当联合治疗的 MPC 与临床药代动力学特征相结合时，在当前剂量方案下，联合治疗可能并不能严格抑制耐药的发生。总之，本研究表明联合治疗是治疗 MDR A. baumannii 感染的一种较好选择。但联合这些药物在当前剂量方案下可能无法预防耐药性出现的发现，需要进一步研究达到耐药预防所需的联合抗生素剂量。
