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Phenotypic testing of AMR

Quality control in AST
Standards development for AST
Challenges in optimizing AST
Petri dish with antibiotics

Quality control in antimicrobial susceptibility testing (AST)

The validity, reproducibility, and accuracy of Antimicrobial Susceptibility Testing (AST) results depend on testing alongside fully characterized strains provided by the American Type Culture Collection (ATCC), the largest culture collection in the world. ATCC strains not only provide quality control for the antibiotics, but also ensure media sterility and accurate identification of organisms throughout the testing process.

Development of AST standards

The guidelines established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical Laboratory Standards Institute (CLSI) serve as the international reference standard for antimicrobial susceptibility testing (AST). These organisations monitor, update, and refine AST methods, breakpoints, and quality control parameters to ensure the accuracy, reproducibility, and reliability of AST processes.

Breakpoint recommendations are based on various factors, including the concentration of the antimicrobial, dosage and dosing regimens, pharmacokinetic and pharmacodynamic data, the site of infection, clinical outcomes, minimum inhibitory concentration (MIC) distributions, epidemiological cut-off values, zone diameter distributions, and the organism’s resistance mechanisms. The guidelines categorize organisms into three groups: susceptible, intermediate, and resistant (S, I, R). The ‘I’ in the EUCAST is ‘Susceptible, increased exposure’, showing therapeutic success with adjusted dose regimen which increases exposure to the antimicrobial. This is referred to as the susceptible-dose dependent (SDD) category in the CLSI. In the SDD category, susceptibility of the organism depends on the dosing regimen used in the patient. Importantly, the CLSI and EUCAST have expert rules and recommendations concerning the methods, antibiotics, and dose/dosing regimens as well as warnings in case AST processes are not performing to the expected standard.

Challenges in optimizing AST

The increase in AMR poses a challenge in optimising Antimicrobial Susceptibility Testing (AST). As resistance levels rise, new mechanisms of resistance may develop that current testing methods cannot detect. Additionally, to effectively combat AMR, there is a pressing need for new antimicrobials and innovative technologies, both of which require thorough validation to ensure their effectiveness.

Discussion Questions
How can the development of new antimicrobials and diagnostic technologies keep pace with the evolving mechanisms of antimicrobial resistance (AMR)?

What are the potential barriers to optimizing antimicrobial susceptibility testing (AST) in the face of emerging resistance?

Please share your opinion in the comments section below, and take part in discussion with other learners.

For further reading, please find the references linked below.

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