On August 21, 2013, the U.S. Food and Drug Administration (FDA) granted 510(k) de novo clearance to the first clinical mass spectrometer for identifying disease-causing bacteria and yeast. The Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometer (MALDI-TOF-MS) was named by the Cleveland Clinic as one of the “Top Ten Breakthrough Medical Technologies of 2013.” While MALDI-TOF mass spec will not change the microbiology lab overnight, it will have a dramatic impact on turnaround times (TATs) and clinical decision making.
According to Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health: “The ability for laboratories to use one device to identify almost 200 different microorganisms is a significant advance in the timely identification of pathogenic microorganisms. Rapid identification of harmful microorganisms can improve the care of critically ill patients.”
The approved MALDI-TOF mass spec platform might be referred to as “smart automation.” It doesn’t simply automate a chore or process that people would otherwise have to do. It actually speeds up the process of diagnosis because MALDI-TOF mass spec can be run at the very first signs of culture growth. Whereas a biochemical method may require distinct and full colony growth, MALDI-TOF mass spec can be run on nascent colonies.
“Compared to other identification methods that require abundant organism growth for testing, mass spectrometry requires only a small amount of yeast or bacterial growth, so testing can start as soon as growth is visible, generally within 18 to 24 hours,” said the FDA. “Traditional methods can take up to five days to produce the same identification results.”
The FDA cleared the MALDI-TOF mass spectrometer to test anaerobic bacteria, Enterobacteriaceae, gram-positive aerobes, fastidious gram-negative bacteria, gram-negative non-Enterobacteriaceae, and yeast. The overall accuracy compared to nucleic acid sequencing for these organisms was 93.6%. The device analyzes material from microbial cultures to provide organism identification. Samples are submitted to multiple laser shots inside the device. The matrix absorbs the laser light and vaporizes, along with the sample, in the process gaining an electrical charge (ionization).
Electric fields then guide the ions into a vacuum tube which separates them according to their weight, with the smaller molecules rising up the column faster than the larger molecules. This “time of flight” creates a series of peaks, which correspond with the different molecules contained in the organism from the sample. All of these peaks create spectra unique to that microorganism. By comparing the spectra to a library, the precise microorganism can be identified very easily.
The impact on the microbiology lab
The impact on the laboratory can be relatively minimal or quite significant, depending on the number of organism-identification methods converted to MALDI-TOF mass spec. Looking at a particular lab’s current organism incident report and the methods used for these identifications will give an idea of how much time MALDI-TOF mass spec will save that lab’s operations. Overall labor savings will depend on daily workload and the time spent on QC for other methods, keeping inventory, maintaining competencies, and providing training.
Cost savings are most significant with the consolidation of reagents, QC, and inventory. There will be increased capacity with current susceptibility testing instrumentation as testing of identification is off-boarded to MALDI-TOF mass spec. Rapid delivery of organism identifications will have the greatest impact on patient care. Many studies indicate that rapid organism identification can reduce the cost of antibiotics, allow for de-escalation of antibiotics that have side effects, and reduce morbidity.
So, does this mean the end of the Petri dish? No, the Petri dish isn’t going anywhere. But, change is coming and microbiologists must prepare for it. In one way, the approval of MALDI-TOF mass spec reveals a lot about microbiology. After all, traditional mass spectrometry has been used in the clinical chemistry lab for a long time, and automation is the norm in hematology labs. What about micro makes it so slow to change?
Simply put, microbiology isn’t a clean and easy science. The microbial world consists of virus, fungi, and bacteria. Bacterial microbes can be spherical or rod-shaped, gram-negative or -positive. Microbiologists attempt to grow colonies on aerobic or anaerobic growth media. They match agar types to sample types in order to provide the most fertile foundation for growth. In other words, microbiology is complicated. Nothing is one-size-fits-all.
However, even a very smart machine can’t simply be dropped into a microbiology pathway that is inefficient. There’s no point in speeding up TATs if the results are going to sit in the LIS for a day or two before being reported. Ensuring that rapid organism ID is getting immediate action from the medical staff will be crucial to the success of MALDI-TOF mass spec implementation in the laboratory.
MALDI-TOF and workflow
With MALDI-TOF mass spec, the current workflow for performing identification will change significantly. First, gram-negative, gram-positive, and yeast can be identified using one methodology rather than multiple methods. This will simplify the number of procedures and steps in the process, as well as the level of competency and training required for the technician. Second, where some of the identifications have been done with additional reagents, panels, or cards, MALDI-TOF will require only a slide and a drop of matrix. This will decrease the number of reagents and inventory needed for identifications, leading to reagent cost savings. Third, as noted, mass spec requires a small amount of a colony formation.
Since MALDI-TOF provides identification in minutes instead of hours, the information flow to the clinician should be more rapid than current methods. Therefore, one should consider what organisms will be going into the MALDI-TOF mass spec pathway, the volume of those tests, and how this new rapid information will be communicated to physicians and incorporated to improve patient outcomes.
I visit hundreds of labs each year to perform LEAN lab assessments, and I see many of the same inefficient behaviors over and over again. For instance, in one lab I visited recently, my colleagues and I counted 69 people involved in specimen processing. While that’s an unusually high number, it’s not at all unusual to see too many people involved in one process. MALDI-TOF mass spec is a wonderful breakthrough with tremendous potential to help patients, but we won’t realize its full potential in the lab when inefficiency is built into the day-to-day pathway of sample collection to pathogen identification. It will not make for a more efficient lab by itself. Only we laboratorians can do that.
Anne Beall, BS, MT(ASCP), serves as Senior Manager, Workflow Optimization and Performance Solutions, for bioMerieux, provider of the VITEK mass spectrometry platform.