As concerns arise that the
vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concurrent
colistin administration, we evaluated the effect of
colistin on
vancomycin efficacy against MRSA via in vitro and in vivo studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCCmec II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the
vancomycin MIC of MRSA following
colistin exposure and evaluated the effect of a
vancomycin-
colistin combination using time-kill assays. We also assessed the in vivo antagonistic effect by administering
vancomycin,
colistin, and a combination of these two in a neutropenic murine thigh
infection model. In the checkerboard assays,
vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 μg/ml following
colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the
vancomycin concentration was twice the MIC. In the murine thigh
infection model with ST5-MRSA and USA100,
vancomycin monotherapy reduced the number of CFU/muscle >1 log10 compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of
colistin on
vancomycin treatment. This study suggests that exposure to
colistin may reduce the susceptibility to
vancomycin of certain MRSA strains. Combination
therapy with
vancomycin and
colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA
infection.