Shields Ryan K, Nguyen M Hong, Potoski Brian A, Press Ellen G, Chen Liang, Kreiswirth Barry N, Clarke Lloyd G, Eschenauer Gregory A, Clancy Cornelius J
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Antimicrob Agents Chemother. 2015 Mar;59(3):1797-801. doi: 10.1128/AAC.03894-14. Epub 2014 Dec 22.
Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 μg/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo.
对于由序列类型258（ST258）、产KPC-2的肺炎克雷伯菌引起菌血症的患者，如果按照以下定义，即当两种药物在体外均无活性时（黏菌素最低抑菌浓度>2μg/ml且存在主要的ompK36孔蛋白突变[氨基酸134和135处鸟嘌呤和丙氨酸插入（aa 134 - 135 GD插入）、IS5启动子插入]或多黏菌素MIC>8μg/ml），碳青霉烯-黏菌素联合治疗方案的治疗失败可能性显著更高（P = 0.007）（P = 0.01）。KPC-肺炎克雷伯菌菌株中的主要ompK36突变是体外和体内碳青霉烯-黏菌素反应的重要决定因素。
