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The New, New Daptomycin Breakpoint for Enterococcus spp.

Romney M Humphries1,2

  • 1Accelerate Diagnostics, Tucson, Arizona, USA rhumphries@axdx.com.

Journal of Clinical Microbiology
|May 17, 2019
PubMed
Summary
This summary is machine-generated.

Clinical and Laboratory Standards Institute revised daptomycin breakpoints for Enterococcus spp. twice in 2019. These changes reflect complex data, including pharmacodynamics and treatment outcomes, posing challenges for accurate laboratory testing.

Keywords:
CLSIEnterococcusbreakpointdaptomycin

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Area of Science:

  • Clinical microbiology
  • Antimicrobial resistance
  • Pharmacodynamics

Background:

  • The Clinical and Laboratory Standards Institute (CLSI) updated daptomycin breakpoints for Enterococcus species in 2019.
  • These revisions followed extensive reviews of in vitro testing, in vivo pharmacodynamics, and clinical outcomes.
  • A key challenge identified was setting breakpoints that balanced pharmacokinetic/pharmacodynamic targets with laboratory testing capabilities.

Purpose of the Study:

  • To analyze the rationale behind the 2019 CLSI daptomycin breakpoint revisions for Enterococcus spp.
  • To highlight the dilemma of bisecting wild-type minimum inhibitory concentration (MIC) distributions.
  • To emphasize the need to consider both pharmacodynamic targets and laboratory test reproducibility.

Main Methods:

  • Review of data including in vitro testing, murine and human in vivo pharmacodynamics, safety of off-label doses, and treatment outcomes.
  • Analysis of pharmacokinetic/pharmacodynamic (PK/PD) modeling results.
  • Evaluation of the impact of breakpoint setting on MIC distribution and laboratory interpretation.

Main Results:

  • Two rapid successive revisions of daptomycin breakpoints for Enterococcus spp. occurred in 2019.
  • A breakpoint bisecting the wild-type Enterococcus faecium MIC distribution presented a significant challenge.
  • The probability of achieving PK/PD targets and the laboratory's ability to generate accurate, reproducible MICs are critical considerations.

Conclusions:

  • Setting antimicrobial breakpoints requires balancing sophisticated PK/PD modeling with practical laboratory testing realities.
  • The 2019 daptomycin breakpoint revisions for Enterococcus spp. illustrate the complexities of antimicrobial stewardship and susceptibility testing.
  • Future breakpoint setting must rigorously address the interplay between pharmacodynamics and the reliability of clinical laboratory measurements.