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Mass Spec for Clinical Microbiology

Infectious diseases remain deadly. In fact, the World Health Organization’s top-ten list of global causes of death includes two examples: lower respiratory infections and HIV. The list stretches much further, to long-standing culprits—including malaria and tuberculosis— and newer perpetrators—including Ebola and
mad cow disease. For public health measures in general and for treating individual patients, clinical microbiologists need fast and effective methods of microbial identification.

Mike May, PhD

Mike May is a freelance writer and editor living in Texas.

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Accuracy, Low Cost, Simplicity and Speed Make this Technology Indispensable in Health Care

According to Robin Patel, professor of medicine and microbiology and chair of the division of clinical microbiology at the Mayo Clinic in Rochester, Minnesota, “Mass spectrometry is being increasingly used in everyday practice in clinical microbiology.”

In 2013 in Nature Reviews Microbiology, Pierre- Edouard Fournier and his French colleagues wrote, “In the twenty-first century, the clinical microbiology laboratory plays a central part in optimizing the management of infectious diseases and surveying local and global epidemiology.” They added, “This pivotal role is made possible by the adoption of rational sampling, point-of-care tests, extended automation, and new technologies, including mass spectrometry.”

Mass spectrometry (MS), though, comes in many forms. The most common type of MS used in clinical microbiology is called matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Another type, called PCR electrospray ionization mass spectrometry, turns PCR-amplified DNA into an aerosol, which is analyzed with MS to determine what has been amplified. This approach can be found in a system called IRIDICA—from Illinois-based Abbott—for direct detection of microorganisms in clinical specimens.

MALDI-TOF MS is a useful approach for identifying colonies of bacteria or fungi. With this technology, the sample is mixed with a matrix and exposed to a laser, which vaporizes and ionizes the sample. The time it takes for the charged particles to reach the detector—the time of flight— depends on their mass-to-charge ratio. Two main companies offer MALDI-TOF MS platforms for clinical microbiology: Massachusetts-based Bruker and France-based bioMérieux.

The clinical advantage

Perhaps most of all, MALDI-TOF MS brings speed to clinical microbiology. Without MALDITOF MS, identifying an infectious bacterium, for example, often took days or more; with MS, a clinical microbiologist needs only a few minutes.

In addition, MS adds accuracy. With MALDI-TOF MS, for example, Patel says, “You can get the right identification.” In addition, you don’t need to know what you’re looking for, be it bacteria or fungus, for instance. The MS output tells you what it is, and very precisely. According to M. Alain Pluquet, corporate vice president and chief technology officer, innovation, for bioMérieux, “Typically for bacteria in a clinical application, the rate of correct identification is 97 percent.”

Beyond that great technological leap, MALDITOF MS also brings an economic incentive to clinical microbiology. Patel says, “It’s cheaper than the past techniques, which required biochemicals, as well as sequencing-based approaches.” Consequently, this technology even changes the workflow in a clinical microbiology lab. Pluquet agrees about the economy. He says, “Basically, identification with MS costs almost nothing.” He adds, “You must buy the machine, but there are no reagents—just slides for the specimens.”

Overall, Patel says, “MALDI-TOF MS is faster [and] cheaper, and it provides for most organisms—not all—the ability to identify an infectious agent more accurately than anything that we had previously.” She adds, “It has changed our clinical practice.”

Simple steps

Not only does MALDI-TOF MS provide fast and accurate answers, but the technology is also easier on the technicians. In addition, “easy to use” is a phrase often attached to MALDI-TOF MS.

Patel says that sample preparation is “super easy.” As she explains, “You take a colony on a plate, use a stick to sample the colony material, put it on a MALDI-TOF MS plate, overlay it with some chemicals, let it dry, and that’s it.”

Even that will be automated one day. Pluquet says, “You will have an autoprep station, so that you can spot slides in minutes with virtually no skill.” That will make this technology incredibly easy from the start.

Although many experts call ESI-MS easy, too, Pluquet says that it’s not as easy as MALDI, a technology bioMérieux has adopted for its MS-based bacterial identification system, VITEK MS. “ESI is more complex,” he says, “The workflow and cost and quality are not comparable to MALDI.”

It’s not just the preparation that matters, but also the analysis. Today’s commercial platforms for using MALDI-TOF MS in clinical microbiology include onboard databases. The system runs the results against the database and puts out an answer. “You don’t even need to look at the mass spectrum,” Patel says.

That database needs to be good and well curated. It must be as representative as possible and kept updated. Still, Patel says, “You can’t identify everything out there, because there are bacteria and fungi that aren’t in the databases.” In addition, if something is not in the database but is similar to something that is, that can cause a misidentification.

Expanding use

MALDI-TOF MS started in clinical microbiology labs in Europe. Now, though, many U.S. labs use this technology as well. A really small hospital lab might not have the volume to justify adopting MALDI-TOF MS. “Aside from that,” says Patel, “it’s a technology that is very useful for most clinical microbiology labs.” In the January 2015 Clinical Chemistry, she wrote “MALDI-TOF MS is an incontrovertibly beneficial technology for the clinical microbiology laboratory.”

The world’s health care systems need these sorts of advances to keep up with the changing world of infectious diseases. As the agents evolve, the technology must adapt. In addition, making this technology easy to use greatly expands the range of use. For example, these forms of MS could be used in developing countries that lack trained technicians. Likewise, these platforms could identify elements of bioterrorism around the world. Public health officials can also apply this technology to epidemiology and, it is to be hoped, identify a local outbreak before it spreads into a pandemic. All these applications benefit from MS, and more surely lie ahead.

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