In Vitro Antibacterial Activity Of Combined Use Of Fosfomycin To Multidrug-resistant Acinetobacter Baumannii

Objective:We aimed to evaluate the in vitro combined antimicrobial effects of fosfomycin with imipenem,minocycline,amikacin,cefoperazone/sulbactam,tegacycline and polymyxin E on clinical isolates of multi-drugresistant Acinetobacter baumannii.Methods:Isolated 30 clinical strains of multi-drugresistant Acinetobacter baumannii,adopting a checkerboard design,broth microdilution assay was used to test the effects of the compounds on the organism.We also determined the single and combination MIC of antibacterial drugs against 30 strains of Acinetobacter baumannii and calculated the fractional inhibitory concentration（FIC）index,to judge the combination effect.Then we will evaluate the advantages and disadvantages of fosfomycin-based combination drug regimen by comparing it with the existing and common combination drug regimens.Results:After the combined application of fosfomycin with imipenem,minocycline,amikacin,cefoperazone/sulbactam,tegacycline and polymyxin E,distribution of the FIC index was as follows:FICI≤0.5 accounting for 56.7%（17/30）,36.7%（11/30）,10%（3/30）,6.7%（2/30）,6.7%（2/30）,6.7%（2/30）;0.5<FICI≤1 accounting for43.3%（13/30）,63.3%（19/30）,43.3%（13/30）,50%（15/30）,56.7%（17/30）,60%（18/30）;1<FICI<4 accounting for 0,0,46.7%（14/30）,43.3%（13/30）,36.7%（11/30）,33.3%（10/30）and there was no antagonistic effect observed.Comparison of fosfomycin combined with imipenem,cefoperazone/sulbactam combined with imipenem,fosfomycin combined with minocycline,cefoperazone/sulbactam combined with minocycline,distribution of the FIC index was as follows:FICI≤0.5 accounting for 56.7%（17/30）,10%（3/30）,36.7%（11/30）,50%（15/30）;0.5<FICI≤1 accounting for 43.3%（13/30）,83%（25/30）,63.3%（19/30）,40%（12/30）;1<FIC<4 accounting for 0,6.7%（2/30）,0,10%（3/30）and there was no antagonistic effect observed.In addition,fosfomycin and cefoperazone/sulbactam both can reduce MIC₅₀ and MIC₉₀ of imipenem and minocycline to a certain extent.Conclusion:Fosfomycin can reduce the MIC value of antibiotics used in combination to varying degrees,especially imipenem and minocycline,followed by amikacin and cefoperazone/sulbactam.Tigacycline and polymyxin E have high sensitivity themselves,so their synergistic and superimposed effects are not obvious.No antagonistic reaction was found in the above combined experiments.The combined regimen of fosfomycin-based antibiotics,compared with the existing and common combination regimens,cefoperazone/sulbactam combined with minocycline has the most advantages and strong synergistic effect,which is superior to fosfomycin combined with minocycline.cefoperazone/sulbactam combined with imipenem was mainly additive and unrelated.In vitro drug sensitivity test showed that the combined effect was inferior to that of fosfomycin combined with imipenem.