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Updated: Apr 23, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
A correlation between reduced susceptibilities to vancomycin and daptomycin among the MRSA isolates selected in
Shigeru Fujimura1, Yoshihisa Nakano2, Akira Watanabe2
1Division of Clinical Infectious Diseases & Chemotherapy, Tohoku Pharmaceutical University, Sendai, Japan; Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Abstract:
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.
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin and daptomycin is increasing. Exposure to either antibiotic can select for resistance to both, necessitating careful drug selection for MRSA infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Recent guidelines recommend daptomycin over vancomycin for certain MRSA infections.
- Increasing prevalence of MRSA isolates with elevated vancomycin minimum inhibitory concentration (MIC) is a growing concern.
- The MIC creeping rate of MRSA strains in Japan significantly increased from 3.3% in 2008 to 13% in 2012.
Purpose of the Study:
- To determine the MIC and mutant prevention concentration (MPC) of daptomycin and vancomycin for clinical MRSA isolates from 2012.
- To investigate the selection of daptomycin- and vancomycin-resistant MRSA strains within the mutant selection window (MSW).
Main Methods:
- Determination of MIC and MPC values for daptomycin and vancomycin against 30 clinical MRSA isolates.
- Analysis of MRSA strains selected within the MSW for both antibiotics.
- Assessment of daptomycin non-susceptibility and vancomycin MIC of 2 μg/mL in selected strains.
Main Results:
- MIC50/MIC80 values for daptomycin and vancomycin were 0.125/0.5 μg/mL and 0.125/1 μg/mL, respectively.
- MPC50/MPC80 values for both antibiotics were 32/64 μg/mL, resulting in an MSW of ≥64 MIC for both.
- Exposure to the MSW of either antibiotic selected for daptomycin non-susceptible isolates (70.0%) and MRSA with vancomycin MIC of 2 μg/mL (26.7%).
Conclusions:
- MRSA isolates with vancomycin MIC of 2 μg/mL and daptomycin non-susceptible strains are selected by exposure to both daptomycin and vancomycin.
- Both daptomycin and vancomycin should be considered for appropriate first-line treatment of MRSA infections, despite vancomycin's frequent use.
Related Concept Videos
Clinical Significance of Antibiotic Resistance
Mechanism of Antibiotic Resistance in MRSA
Antibiotic Selection
Development of Antibiotic Resistance

