CME February – Application of MALDI-TOF MS in Clinical Microbiology

Dr. Subodha Wickramasinghe (MD), Lecturer, Department of Microbiology, Faculty of Medicine, University of Ruhuna Delivered a lecture on “Application of MALDI-TOF MS (Matrix Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry) in Clinical Microbiology ” . 01st of February 2019 .

A rapid and accurate microbiological diagnosis is associated with decreased mortality and reduced length of hospitalization, especially for severe, life threatening infections. This also allows for early streamlining of empirical antimicrobial therapies, contributing to limit the emergence and spread of antimicrobial resistance.
The introduction of matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) for routine identification of microbial pathogens has profoundly influenced microbiological diagnostics, and is progressively replacing biochemical identification methods.

Compared to currently used identification methods, MALDI-TOF MS has the advantage of identifying bacteria and yeasts directly from colonies grown on culture plates for primary isolation in a few minutes and with considerable material and labor savings. The reliability and accuracy of MALDI-TOF MS in identification of clinically relevant bacteria and yeasts have been demonstrated by several studies showing that the performance of MALDI-TOF MS is comparable or superior to phenotypic methods currently in use in clinical microbiology laboratories, and can be further improved by regular database updates and analysis software upgrades.

Even though the DNA sequencing can identify fastidious and uncultivable microorganisms, the requirement of trained laboratory personnel, powerful interpretation soft wares, expensive materials, makes it less suitable for routine clinical use.
In comparison, MALDI TOF MS requires high initial cost for the MALDI-TOF equipment. But the ability to obtain an accurate microbiological diagnosis within a few minutes without trained laboratory personnel and reduced cost per test and reduced hands-on-time allows MALDI-TOF MS system more superior than other detection methods in a clinical microbiology laboratory.

Other limitations of MALDI TOF MS are the limit of resolution among closely related organisms like Shigella and E.coli, similarities of spectra present in the database as for viridans streptococci and pneumococci and for yeasts requiring a protein extraction procedure for correct identification as insufficient protein signal by direct colonies.
At present many laboratories rely on MALDI-TOF MS for routine identification of microbial pathogens, and use other identification systems like genome sequencing to confirm uncertain (low-score value by MALDI-TOF MS) identifications to achieve correct identification rates.
Besides microbial identification from isolated colonies, new perspectives are being explored for MALDI-TOF MS, such as identification of pathogens directly from positive blood cultures, sub-species identification and strain typing, assessment of drug susceptibility and detection of drug resistance determinants.

In conclusion, MALDI-TOF MS is a tool for rapid, accurate, and cost-effective identification of microorganisms and applicable to a broad range of common as well as esoteric bacteria including mycobacterial spp. and fungi and has become an incontrovertibly beneficial technology in a clinical microbiology laboratory.

Florio W, Tavanti A, Barnini S, Ghelardi E and Lupetti A (2018)Recent Advances and Ongoing Challenges in the Diagnosis of Microbial Infections by MALDI-TOF Mass Spectrometry. Front. Microbiol. 9:1097.
doi: 10.3389/fmicb.2018.01097
Robin Patel (2015). MALDI-TOF MS for the Diagnosis of Infectious Diseases, Clinical Chemistry 61:1 100–111