When Combined with Colistin, an Otherwise Ineffective Rifampicin–Linezolid Combination Becomes Active in Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii

The synergistic action of colistin, with two antibiotics active in Gram-positive bacteria but unable to kill gram negatives (linezolid and rifampicin), was investigated, since triple combinations are emerging as a tool to overtake multidrug resistance. Checkerboard determinations demonstrated that, when combined with colistin, the combination of linezolid and rifampicin turns active in multidrug-resistant Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Thus, the presence of sublethal concentrations of colistin resulted in a strongly synergistic interaction between these two drugs. Moreover, the minimum inhibitory concentrations of linezolid–rifampicin combinations in the presence of colistin were lower than the maximal concentrations of these antimicrobials ain blood. These findings suggest the use of this triple combination as an effective treatment of multidrug-resistant (MDR) bacterial infections.