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A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
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Antimicrobial susceptibility breakpoints: PK-PD and susceptibility breakpoints

Paul G Ambrose1

  • 1Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York 12208, USA. PAmbrose-ICPD@OrdwayResearch.org

Treatments in Respiratory Medicine
|April 23, 2005
PubMed

Insights

Standardizing antimicrobial susceptibility testing remains challenging. Pharmacokinetics-pharmacodynamics can help interpret results for resistant bacteria like Streptococcus pneumoniae, guiding effective treatment choices.

Area of Science:

  • Clinical Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Standardization of antimicrobial susceptibility testing has advanced since the 1960s.
  • Interpretation of susceptibility test results remains controversial, impacting clinical decisions.
  • Penicillin-resistant Streptococcus pneumoniae emerged, leading to macrolides as alternative treatments.

Purpose of the Study:

  • To address the ongoing debate regarding the interpretation of clinical laboratory susceptibility test results.
  • To explore the clinical meaning of increasing macrolide minimum inhibitory concentration (MIC) values in Streptococcus pneumoniae.
  • To utilize pharmacokinetics-pharmacodynamics (PK-PD) for optimizing antimicrobial breakpoints and treatment regimens.

Main Methods:

  • Review of historical advancements in antimicrobial susceptibility testing standardization.
  • Analysis of the emergence and clinical impact of resistant Streptococcus pneumoniae strains.
  • Application of pharmacokinetic-pharmacodynamic principles to interpret MIC values and guide breakpoint selection.

Main Results:

  • Discordance between interpretive test results and clinical response has been observed.
  • Increasing incidence of pneumococcal isolates with elevated macrolide MIC values noted.
  • Pharmacokinetics-pharmacodynamics offers a framework for interpreting elevated MICs and selecting appropriate breakpoints.

Conclusions:

  • Pharmacokinetics-pharmacodynamics is crucial for interpreting antimicrobial susceptibility testing results, especially for resistant pathogens.
  • PK-PD modeling aids in determining appropriate dosing regimens for contemporary antimicrobial agents.
  • Accurate interpretation of susceptibility data is essential for effective antimicrobial therapy and selection of breakpoints.

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