In vitro evaluation of antibiotic synergy for NDM-1-producing Enterobacteriaceae

Objectives: To analyse the in vitro activity of colistin, fosfomycin and tigecycline alone or in combination against enterobacterial NDM-1 producers. Methods: MIC values of colistin, fosfomycin and tigecycline were determined for 28 NDM-1-producing enterobacterial isolates. In vitro synergy combination testing was performed for eight clinical isolates and one Escherichia coli transconjugant (six being susceptible to the three antibiotics) using microdilution and chequerboard techniques. Results: MICs of colistin, fosfomycin and tigecycline were determined, showing that one-third of NDM-1-producing isolates were resistant or intermediate to at least one of the three drugs. Nevertheless, in vitro synergistic activity was observed for colistin plus fosfomycin and colistin plus tigecycline in very rare cases. Conclusions: Synergistic activity was observed for colistin and fosfomycin, and colistin and tigecycline in rare cases, most of the interactions being indifferent.