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Susceptibility testing of the polymyxins: where are we now?
1Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California; Clinical Microbiology, UCLA Health System, Los Angeles, California.
Abstract:
Antimicrobial susceptibility testing for the polymyxins-colistin and polymyxin B-is fraught with technical challenges. Key among these is the propensity of the polymyxins to adsorb to polystyrene, a material often used for in vitro minimum inhibitory concentration testing devices. This effect may be mitigated by the addition of a surfactant such as polysorbate 80; however, concern exists that polysorbate 80 may act synergistically with the polymyxins and artificially lower minimum inhibitory concentrations. Furthermore, the polymyxins diffuse poorly through agar, compromising the performance of both disk diffusion and Etest methods. Very few peer-reviewed studies have investigated in vitro susceptibility test methods for the polymyxins, and it is clear that an in vitro test that reliably predicts the activity of the polymyxins in vivo has yet to be defined. This review describes the methods available and challenges associated with susceptibility testing of colistin and polymyxin B and discusses the current breakpoints for both agents.
Insights
Accurate antimicrobial susceptibility testing for polymyxins like colistin is challenging due to drug adsorption and poor diffusion. Reliable in vitro methods predicting in vivo activity are still undefined.
Area of Science:
- Microbiology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Polymyxins (colistin and polymyxin B) are critical last-resort antibiotics.
- Antimicrobial susceptibility testing (AST) for polymyxins faces significant technical hurdles.
- Accurate AST is essential for guiding effective treatment of multidrug-resistant Gram-negative infections.
Purpose of the Study:
- To review current in vitro susceptibility testing methods for colistin and polymyxin B.
- To highlight the technical challenges associated with polymyxin AST.
- To discuss the current clinical breakpoints for these agents.
Main Methods:
- Review of peer-reviewed literature on polymyxin susceptibility testing.
- Analysis of factors affecting test accuracy, including drug adsorption and diffusion.
- Discussion of various AST methodologies (e.g., MIC testing, disk diffusion, Etest).
Main Results:
- Polymyxins adsorb to polystyrene, impacting minimum inhibitory concentration (MIC) results.
- Surfactants like polysorbate 80 may mitigate adsorption but raise concerns of synergy.
- Poor diffusion of polymyxins through agar compromises disk diffusion and Etest performance.
- An in vitro test reliably predicting in vivo polymyxin activity remains undefined.
Conclusions:
- Current in vitro methods for polymyxin susceptibility testing are unreliable.
- Further research is needed to develop and validate accurate AST methods for colistin and polymyxin B.
- Standardized and validated polymyxin AST methods are crucial for clinical decision-making.
