A correlation between reduced susceptibilities to vancomycin and daptomycin among the MRSA isolates selected in mutant selection window of both vancomycin and daptomycin

Guidelines for the treatment of MRSA infection, recently published by the IDSA and JSC, recommend daptomycin for sepsis and skin and soft tissue infections comparably to or more strongly than vancomycin. Meanwhile MIC creeping with an increased isolation frequency of MRSA isolates with vancomycin MIC of 2 μg/mL has become a problem. In the present study, the MIC creeping rate of MRSA strains in the Tohoku district, Japan in 2012 was 13%, a significantly higher value than 3.3% in 2008 (P < 0.01). Of these isolates, the MIC and mutant prevention concentration (MPC) values of daptomycin and vancomycin were determined for 30 clinical isolates of MRSA in 2012. The MIC₅₀/MIC₈₀ values of daptomycin and vancomycin were 0.125/0.5 μg/mL and 0.125/1 μg/mL, respectively. The MPC₅₀/MPC₈₀ values of daptomycin and vancomycin were both 32/64 μg/mL. In the present study, the mutant selection window (MSW) of daptomycin and vancomycin was ≥64 MIC. Of strains that selected in the MSW, daptomycin non-susceptible isolates accounted for 70.0%, while MRSA with vancomycin MIC of 2 μg/mL accounted for 26.7%. On the other hand, 50% of the strains that selected in the vancomycin MSW were daptomycin non-susceptible strain. The detection rate of MRSA with vancomycin MIC of 2 μg/mL that selected in the daptomycin MSW was 36.7%. These results showed that MRSA with vancomycin MIC of 2 μg/mL and daptomycin non-susceptible isolates were selected by exposure to both antibiotics. Therefore, though vancomycin is frequently used for treatment of MRSA infection, both antibiotics should be selected as a first-line drug appropriately.