MS makes identification of clinical pathogens a cinch

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Someday, pathogen identification in the clinic may take minutes instead of hours. Experts say that MALDI TOFMS with special software is poised to displace traditional biochemical tests for pathogen identification in clinical laboratories within the next 5 years. Over the past 2 years, several clinical settings in Europe and the U.S. have been testing the technology. “This is the first time that a MALDI TOF pattern-recognition modality has made its way into the [clinical] laboratory,” says Andy Hoofnagle at the University of Washington.

MS has been used for years in clinics for small-molecule measurements. But products specifically targeted for pathogen identification have experts optimistic that the days of juggling various biochemical assays are numbered. “It’s a robust, reproducible molecular result that’s going to answer that question of ‘What do I have in here?’, not, ‘Do I have this [particular] bug in here?’,” states George Goedesky of Bruker Daltonics.

Vendors such as Bruker Daltonics and Shimadzu (in collaboration with AnagnosTec) have entered this market with the MALDI Biotyper and the AXIMA@SARAMIS, respectively. The products are based on MALDI TOFMS with software programs that match spectra from samples to those in built-in databases. Both products identify all kinds of microorganisms from standard cultures. Users can either purchase a commercial library or create their own references.

The MALDI Biotyper, explains Gary Kruppa of Bruker Daltonics, is a protein mass fingerprinting method that matches spectra from samples to library spectra. High-abundance proteins, such as ribosomal and other housekeeping proteins, are usually identified because they are expressed under all growth conditions and yield reproducible patterns. SARAMIS (short for Spectral Archiving and Microbial Identification System) looks at the microorganism’s proteome for the match.

Hoofnagle and Patrick Murray at the National Institutes of Health admit to being skeptical about the technique initially. A challenge in microbiology is that “organisms grow on a variety of different media. You would anticipate they may express different proteins and surface antigens growing on the different media. You might get very different profiles,” explains Murray.

But Murray became a convert because “the profiles are incredibly reproducible. We have found it’s a very robust system, and we can use any organism that we’ve grown on virtually any media that we’ve looked at so far.”

Time is another factor. “If MS can pull it off, it will be minutes, instead of hours, to identify a colony from a plate,” says Hoofnagle. The time savings is critical in a hospital. “The fact [that] you can tell what type of bacteria you are facing much earlier is fantastic because you know which antibiotic to give,” says Denis Hochstrasser at the University of Geneva and Geneva University Hospital. “Antibiotics cost millions to hospitals. If you can narrow [it down] from a highly expensive, broad-spectrum antibiotic to a more adapted and efficient antibiotic, you save money, and it’s better for the patient.”

Biochemical tests have been commonly regarded as reasonably reliable techniques. But when Murray’s group launched a gene-sequencing program, considered to be the gold standard for microorganism identification, they discovered that in many cases microorganisms were misidentified by the biochemical tests. Murray’s group then compared their MS identifications with the gene-sequencing data. “What we found was that the MALDI TOFMS—once we built a database and used the database the company had built—was remarkably accurate. In fact, when we compared the initial biochemical identification with the MALDI TOFMS identification, if we saw a discrepancy, invariably the MS identification was confirmed by gene sequencing.”

Akos Vertes of George Washington University is optimistic that MS will improve medical service and reduce costs but notes that some changes have to occur before the technology will become entrenched. “The instrument manufacturers need to produce instruments more in line with the budget of clinical units. Other factors include the training of personnel in clinical laboratories and the lack of standardized protocols based on MS.”

Experts say the MS systems should also ideally be combined with antibiotic-susceptibility assays. Some biochemical assays currently provide both identification and susceptibility data, and some researchers hope that manufacturers will design a platform to provide both functions.

It’s early yet, but experts are encouraged that these MS systems will become established. “The writing is on the wall,” says Scott Kuzdzal of Shimadzu. “Laboratories have already decided that this technology, because of its speed and cost, is going to play a role in the clinic.”

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This article has been cited by 1 ACS Journal articles (1 most recent appear below).

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  Rapid Sample Preparation for Microorganism Analysis by Mass Spectrometry

  Franco Basile
  2011 (), 5-34

  • Rapid Sample Preparation for Microorganism Analysis by Mass Spectrometry

    Franco Basile
    2011 (), 5-34

    The time required for rapid microorganism analysis by Mass Spectrometry (MS) should take into account not only the time devoted to perform the measurement, but also the time to prepare the biological sample (including growth and isolation) and perform the ...

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