“Antimicrobial Susceptibility Testing on MALDI-TOF: The Holy Grail”

We already know that Maldi-tof is a “no brainer” for most routine diagnostic microbiology labs. (Click here for a nice article on the realities of putting a Malditof instrument into a diagnostic laboratory)MALDITOF

However if we could also perform anti-microbial susceptibility testing on Maldi-tof in addition to microbe identification, then it would take it to another level altogether…

There has been a lot of recent work in this area. A nice paper  in Clinical Microbiology Reviews summarises this work. (Unfortunately it is not free to access. Here is the abstract. I hope your institution can obtain it for you.)

I will summarise where the research is at:

  1. Detection of carbapenemases: This is progressing well. the technique involves incubating the bacteria and the carbapenem, and then analysing the products with Malditof. If the bacteria contains a carbapenemase that can lyse the carbapenem then the specific spectra for the degradation products of the carbapenem can be detected. Similar methods are also being developed to look for other beta-lactamases as well as aminoglycoside modifying enzymes.
  2. Detection of MRSA (Methicillin Resistant Staphylococcus Aureus). Specific spectral peaks for MRSA are identifiable, but are quite subtle and difficult to reproduce in a consistent manner at present. More work needed.
  3. Detection of VRE (Vancomycin Resistant Enterococci). Detection of the Van A and Van B “genotypes” now well validated in a research setting. Should not be too long before this becomes routine in diagnostic laboratories.
  4. Detection of ESBLs (Extended Spectrum Beta Lactamases): Difficult… A newer technique named mini-sequencing may have potential. This involves using the fact that specific mutations produce specific differences in molecular mass. However it require DNA amplification and still quite labour and time intensive. This technique could also be used to detect mutations responsible for resistance in Neisseria gonorrhoeae, Streptococcus pneumoniae etc.

It looks like VRE detection and carbapenemase detection are the most likely to become routine Maldi-tof techniques in diagnostic laboratories over the next few years. MRSA detection I suspect is not too far away either. The rest is going to take some time and the paper concludes that proteomic approaches in the detection of resistant organisms is only ever likely to complement, not replace, standard susceptibility testing.

Michael

p.s If you are a student studying for microbiology exams in the next year or two, I would advise that you ensure you know all about Maldi-tof! In addition, knowledge of future potential applications is likely to separate out the distinction candidates from the passes….

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