Polymyxin Susceptibility Testing and Breakpoint Setting.

Susceptibility testing of polymyxins has been subject to intensive review and revision in recent years. A joint working group was established by the Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing to establish a reference method. Issues examined included the effects of divalent cations, binding to laboratory materials, and addition of polysorbate 80. The working group recommended the use of broth microdilution without the addition of polysorbate 80 as the reference method. Published studies have shown that other testing methods, including agar dilution, disk diffusion and gradient diffusion, have unacceptably high levels of very major errors compared to the reference method, and are not recommended for routine laboratory use. Most data were for the testing of colistin; less information was available for polymyxin B. The joint working group was also asked to consider the setting of clinical breakpoints for relevant pathogens. This task involved examination of the available pharmacokinetic-pharmacodynamic, pharmacokinetic-toxicodynamic and population clinical pharmacokinetic data. All current pharmacokinetic-pharmacodynamic targets are based on MICs generated using the reference broth dilution procedure.