An update on the routine application of MALDI-TOF MS in clinical microbiology

ABSTRACT

Introduction: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has entered clinical diagnostics and is today a generally accepted and integral part of the workflow for microbial identification. MALDI-TOF MS identification systems received approval from national and international institutions, such as the USA-FDA, and are continuously improved and adopted to other fields like veterinary and industrial microbiology. The question is whether MALDI-TOF MS also has the potential to replace other conventional and molecular techniques operated in routine diagnostic laboratories.

Areas covered: We give an overview of new advancements of mass spectral analysis in the context of microbial diagnostics. In particular, the expansion of databases to increase the range of readily identifiable bacteria and fungi, the refined discrimination of species complexes, subspecies, and types, the testing for antibiotic resistance or susceptibility, progress in sample preparation including automation, and applications of other mass spectrometry techniques are discussed.

Expert opinion: Although many new approaches of MALDI-TOF MS are still in the stage of proof of principle, it is expectable that MALDI-TOF MS will expand its role in the clinical microbiology laboratory of the future. New databases, instruments and analytical software modules will continue to be developed to further improve diagnostic efficacy.

KEYWORDS:

• MALDI-TOF MS
• microbial taxonomy
• species complex
• typing
• sample preparation
• antibiotic susceptibility testing
• next generation MS

Acknowledgments

We are very grateful for the continual support of Valérie Monnin and Nadine Perrot on various MALDI-TOF MS projects. We would also like to thank Katleen Vranckx for her detailed analyses of spectra from the Mycobacterium tuberculosis complex.

Article highlights

• Over the past 15 years, more than 5000 MALDI-TOF MS instruments have been introduced in clinical microbiology laboratories worldwide.

• Pre-analytical sample management for MALDI-TOF MS is essentially simple when bacterial identification is involved; for more upfront application of MALDI TOF MS, sample preparation still needs further optimization.

• Enrichment of diagnostic MALDI-TOF MS databases requires continued (taxonomic) attention although the initial urgency waned.

• Certified and quality controlled MALDI-TOF MS databases are an absolute must whereas confidentiality and privacy need to be well protected. Increasingly “intelligent” software packages need to be developed to facilitate broader microbiological exploitation of the power of MALDI-TOF MS

• Increasingly “intelligent” software packages need to be developed to facilitate broader microbiological exploitation of the power of MALDI TOF MS

• Antimicrobial Susceptibility Testing by MALDI TOF MS has passed the stage of proof of principle although real clinical application is still in the early stages.

• Next generation MS is still hampered by slow turn-around time, costliness and technical complexity.

Declaration of interest

All authors are employees of bioMérieux. The company was not involved in the design of the current review and the opinions expressed are those of the authors and may be different from formal company opinions and policies.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by bioMérieux, a company designing, developing and marketing tests in the domain of infectious diseases.