Polymyxin Susceptibility Testing and Breakpoint Setting

Area of Science:

• Clinical Microbiology
• Antimicrobial Susceptibility Testing

Background:

• Polymyxin susceptibility testing methods have undergone recent revisions.
• A joint working group was formed by CLSI and EUCAST to establish a reference method.
• Key issues included divalent cations, binding to lab materials, and polysorbate 80.

Purpose of the Study:

• To establish a standardized reference method for polymyxin susceptibility testing.
• To evaluate alternative testing methods against the reference standard.
• To consider clinical breakpoint setting for relevant pathogens.

Main Methods:

• Broth microdilution without polysorbate 80 was recommended as the reference method.
• Evaluation of agar dilution, disk diffusion, and gradient diffusion methods.
• Analysis of pharmacokinetic-pharmacodynamic (PK-PD) and PK-toxicodynamic data.

Main Results:

• Broth microdilution without polysorbate 80 demonstrated superior accuracy.
• Alternative methods (agar dilution, disk diffusion, gradient diffusion) exhibited high rates of very major errors.
• Most data focused on colistin, with less available for polymyxin B.

Conclusions:

• Broth microdilution without polysorbate 80 is the recommended reference method for polymyxin susceptibility testing.
• Alternative methods are not advised for routine laboratory use due to significant error rates.
• Current PK-PD targets rely on MICs derived from the reference broth dilution procedure.