Antimicrobial susceptibility breakpoints: PK-PD and susceptibility breakpoints.

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.