Synergistic activity of colistin and fosfomycin combination against carbapenemase-producing Klebsiella pneumoniae in an in vitro pharmacokinetic/pharmacodynamic model
Carbapenemase producing Klebsiella pneumoniae has become a significant public health concern and combination therapy may be the chemotherapeutic option.This study aimed to evaluate the fosfomycin and colistin combination against carbapenemase producing K.pneumoniae.The antibacterial effects were determined in an in vitro pharmacokinetic model by timekill studies over 24 hours.The initial inoculum was 108 CFU/mL.Low,medium and highCmaxvalues of colistin at 0.5,2,5 mg/L respectively,and Cmaxof fosfomycin at 100mg/Lweresimulated in the model.Doses of both colistin and fosfomycin were given every 8 h until 24 h.Forthe colistin and fosfomycin susceptible isolateKP47,three combination regimens showed greater killing compared with colistin alone.The greatest killing was observed in colistin 5mg/L combination regimen with 3-6 log CFU reduction.For colistin-heteroresistant and fosfomycin susceptible isolateKP79,combination of low dosage colistin(0.5mg/L)regimen with fosfomycin showed no synergistic or additive effects.However,combination therapy of colistin at 2 and 5 mg/L can maintained the bactericidal effect until 24 hours compared with colistin monotherapy that allowed regrowth after 12h.For colistin-heteroresistant and fosfomycin resistant isolates KP42 and KP11,little enhancement of bactericidal activity was observed in combinationregimens.5 mg/L colistin in combination with fosfomycin could only prevent the emergence of colistinresistant isolates in those isolatesthat are sensitive to colistin.Clinical practice of colistin and fosfomycin against carbapenemase-producing K.pneumoniae need to be cautious and must be based on the susceptibility results.
Yun Cai Ji-tong He Yan Bai Rui Wang Jin Wang
Center of Medicine Clinical Research,Department of Pharmacy,PLA General Hospital,Beijing,China
国内会议
西安
英文
49-61
2017-11-04（万方平台首次上网日期，不代表论文的发表时间）