Di Xiuzhen, Wang Rui, Liu Bin, Zhang Xin, Ni Wentao, Wang Jin, Liang Beibei, Cai Yun, Liu Youning
The Center of Medicine Clinical Research, Translational Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
J Antibiot (Tokyo). 2015 Sep;68(9):551-5. doi: 10.1038/ja.2015.27. Epub 2015 Mar 25.
The shortage of effective antibiotics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a public health threat. Combination treatment may represent a good choice for treating infections caused by CRPA. The aim of this study was to evaluate the in vitro efficacy of fosfomycin in combination with colistin against clinical CRPA isolates. Eighty-seven isolates were collected from three hospitals in China. The checkerboard method and time-kill assay were used to assess the interactions between fosfomycin and colistin. The fosfomycin/colistin combination displayed synergistic and partial synergistic activity against 21.84% and 27.59% of the isolates, respectively. Antagonism was not observed. In combination, the colistin MIC values were ⩽0.5 μg ml(-1) for 91.95% of the isolates. This result differed significantly from those obtained using a single agent treatment (The colistin MIC values were ⩽0.5 μg ml(-1) for only 25.29% of the isolates). In addition, the time-kill assay demonstrated that the fosfomycin/colistin combination treatment exerted bactericidal effects against five isolates and that the regrowth observed after colistin monotherapy was prevented. In summary, the combination of fosfomycin and colistin demonstrated synergistic activity against the CRPA isolates tested in this study. Furthermore, fosfomycin may potentially widen the therapeutic window of colistin, suggesting that this combination could be applied clinically to control infections caused by CRPA.
针对耐碳青霉烯类铜绿假单胞菌（CRPA）的有效抗生素短缺对公共卫生构成了威胁。联合治疗可能是治疗CRPA引起的感染的一个不错选择。本研究的目的是评估磷霉素与黏菌素联合对临床CRPA分离株的体外疗效。从中国的三家医院收集了87株分离株。采用棋盘法和时间杀菌试验评估磷霉素与黏菌素之间的相互作用。磷霉素/黏菌素联合对分别21.84%和27.59%的分离株显示出协同和部分协同活性。未观察到拮抗作用。联合使用时，91.95%的分离株的黏菌素MIC值≤0.5μg/ml-1。这一结果与单药治疗所得结果有显著差异（仅25.29%的分离株的黏菌素MIC值≤0.5μg/ml-1）。此外，时间杀菌试验表明，磷霉素/黏菌素联合治疗对五株分离株发挥了杀菌作用，并防止了黏菌素单药治疗后观察到的细菌再生长。总之，磷霉素和黏菌素联合对本研究中测试的CRPA分离株显示出协同活性。此外，磷霉素可能会扩大黏菌素的治疗窗，表明这种联合可在临床上用于控制CRPA引起的感染。
