Does the activity of the combination of imipenem and colistin in vitro exceed the problem of resistance in metallo-beta-lactamase-producing Klebsiella pneumoniae isolates?

Using time-kill methodology, we investigated the interactions of an imipenem-colistin combination against 42 genetically distinct Klebsiella pneumoniae clinical isolates carrying a bla(VIM-1)-type gene. Irrespective of the imipenem MIC, the combination was synergistic (50%) or indifferent (50%) against colistin-susceptible strains, while it was antagonistic (55.6%) and rarely synergistic (11%) against non-colistin-susceptible strains (with synergy being observed only against strains with colistin MICs of 3 to 4 microg/ml). The combination showed improved bactericidal activity against isolates susceptible either to both agents or to colistin.