Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing Position...

Area of Science:

• Pharmacology
• Infectious Diseases
• Microbiology

Background:

• Recent data indicate polymyxins possess limited clinical utility.
• Pharmacokinetic and pharmacodynamic (PK/PD) studies highlight challenges in achieving effective bacterial killing concentrations.
• Polymyxin use is associated with significant nephrotoxicity and increased mortality.

Purpose of the Study:

• To review current data on polymyxin utility.
• To discuss the differing perspectives of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) regarding polymyxin susceptibility criteria.
• To inform the clinical community on the evolving landscape of polymyxin use.

Main Methods:

• Review of recent pharmacokinetic, pharmacodynamic, toxicity, and clinical outcome data for polymyxins.
• Analysis of in vitro susceptibility data and interpretive criteria set by CLSI and EUCAST.
• Examination of randomized and observational studies comparing polymyxins to alternative agents.

Main Results:

• A steady-state concentration of 2 μg/mL is required for bacterial killing, but less than 50% of patients achieve this, risking nephrotoxicity.
• This exposure level is insufficient for bacterial stasis in pneumonia models.
• Studies consistently show higher mortality with polymyxins versus alternatives.
• CLSI has removed the "susceptible" category for polymyxins, while EUCAST retains it.

Conclusions:

• Polymyxins demonstrate limited clinical utility due to PK/PD limitations, toxicity, and increased mortality.
• Divergent approaches by CLSI and EUCAST in setting susceptibility criteria reflect ongoing debate and data interpretation.
• Clinicians should carefully consider polymyxin risks and benefits against alternative therapies.