Investigation Of Resistance Mechanisms And The Treatment Strategies For Carbapenem-Resistance Citrobacter Freundii

Objective:By summarizing the clinical data of carbapenem-resistant C.freundii,analyzing the drug resistance mechanisms,looking for the reasonable and effective treatment methods,to provide reference and medication basis for clinicians.Methods:All the carbapenem-resistant C.freundii isolates were collected and identified from the hospital among 2013 to 2016.For each isolate,the clinical information was gathered.The modified Hodge test and EDTA double-disk synergy test were used to screen for the carbapenem resistant phenotypes.Carbapenemase resistant genes were analyzed by polymerase chain reaction（PCR）for all the isolates.The agar dilution method and the broth dilution method were used to determine the minimal inhibition concentration（MIC）of fosfomycin alone and in combination,the effect of combination was assessed by fractional inhibitory concentration index（FICI）.Results:In this study,a total of 17 carbapenem-resistant C.freundii isolates were collected from the hospital.All of the CNS C.freundii strains were shown to be carbapenemase-producers as revealed by the modified Hodge test.Additionally,all isolates showed enlarged inhibition zones around carbapenem disks in the presence of EDTA.8 isolates were found to carry bla_NDM-1DM-1 and 9 isolates were detected to harbor bla_IMP.bla_KPC,bla_SPM and bla_OXA-48XA-48 were not found in the study.The combination of fosfomycin and imipenem demonstrated 75%synergism and additive effect,it should be noted that only the synergism effect has been found 56.25%.About the combination of fosfomycin and cefoperazone/sulbactam,the synergism and additive effect was 50%.Conclusion:The modified Hodge test and EDTA double-disk synergy test had high sensitivity in detection of carbapenem-resistant phenotype;Fosfomycin combined with imipenem or cefoperazone/sulbactam in vitro have good antibacterial activity,but imipenem combined with fosfomycin may be better.