Innovative and rapid antimicrobial susceptibility testing systems

Abstract

Antimicrobial resistance (AMR) is a major threat to human health worldwide, and the rapid detection and quantification of resistance, combined with antimicrobial stewardship, are key interventions to combat the spread and emergence of AMR. Antimicrobial susceptibility testing (AST) systems are the collective set of diagnostic processes that facilitate the phenotypic and genotypic assessment of AMR and antibiotic susceptibility. Over the past 30 years, only a few high-throughput AST methods have been developed and widely implemented. By contrast, several studies have established proof of principle for various innovative AST methods, including both molecular-based and genome-based methods, which await clinical trials and regulatory review. In this Review, we discuss the current state of AST systems in the broadest technical, translational and implementation-related scope.

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Fig. 1: Schematic overview of antimicrobial susceptibility testing and antimicrobial resistance detection methods.
Fig. 2: New phenotypic methods: microbial characteristics along with restricted survey and description of the mechanisms of new phenotypic methods to help overcome the limitations of current methods.
Fig. 3: Molecular antimicrobial susceptibility testing assays.

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Acknowledgements

The authors gratefully acknowledge A. Hemmert (BioFire, Salt Lake City, UT, USA) for his insightful review of the text.

Author information

A.v.B., O.R. and W.M.D. researched data for the article. A.v.B., C.-A.D.B., F.M., O.R. and W.M.D. wrote the article. A.v.B., C.-A.D.B., J.W.A.R., F.M. and W.M.D. substantially contributed to discussion of the content. A.v.B, C.-A.D.B., J.W.A.R. and W.M.D. reviewed and edited the manuscript before submission.

Correspondence to Alex van Belkum.

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Competing interests

A.v.B., F.M. and O.R. are employees at bioMérieux, a company that designs, markets and sells antimicrobial susceptibility testing tools and systems. C.A.B. has received research support from bioMérieux, BioFire, Cepheid, Accelerate Diagnostics, Luminex, Bio-Rad Laboratories, Thermo Fisher and SeLux.

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Nature Reviews Microbiology thanks R. Cantón, J. O’Grady, M. Fernandez Suarez and M. Sanguinetti for their contribution to the peer review of this work.

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Related links

Comprehensive Antibiotic Resistance Database (CARD): https://card.mcmaster.ca

EUCAST: www.eucast.org/organization

EUCAST standardized rapid-AST protocols: www.eucast.org/rapid_ast_in_blood_cultures

ResFinder: https://cge.cbs.dtu.dk/services/ResFinder

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Glossary

Minimal inhibitory concentration

(MIC). The lowest concentration of an antimicrobial agent that prevents visible growth of a bacterium species or isolate. The MIC is defined by combined activities of the microorganism, the affected patient and the antimicrobial agent itself.

Lag phase

The temporary period in which microorganisms are adapting to a new environment, avoiding threats and metabolizing, and increasing in cell size but not yet actively dividing and multiplying. During this period, cells are synthesizing enzymes and other factors needed for actual cell division under the new environmental conditions.

Tolerance

The microbial ability to resist being killed by antimicrobials. This ability is distinct from (multi)drug resistance and is not caused by mutant microorganisms, but rather by cells existing in a dormant, non-dividing state.

Zone of inhibition

If bacteria are grown as layers on solid growth media and an antibiotic stops the bacteria from growing or kills them, there will be an area around the place where the antibiotic has been positioned (usually in a well or on a paper disc) where the bacteria have not grown enough to be visible. The radius of such a region of growth inhibition is correlated with the level of antibiotic susceptibility of the strain being tested.

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van Belkum, A., Burnham, C.D., Rossen, J.W.A. et al. Innovative and rapid antimicrobial susceptibility testing systems. Nat Rev Microbiol (2020). https://doi.org/10.1038/s41579-020-0327-x

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