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.

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.

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