Four years ago in this space, my colleague Anne Beall wrote about the introduction of mass spectrometry into the microbiology laboratory.1 Her column was forward-looking, because it came just two months after the U.S. Food and Drug Administration (FDA) granted 510(k) de novo clearance to the first matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometer for clinical use in the identification of disease-causing bacteria and yeast.2
There was a great deal of enthusiasm about this approval because it was the first fundamentally new technology introduced to clinical microbiology labs in many years. The Cleveland Clinic named MALDI-TOF MS as one of the “Top Ten Breakthrough Medical Technologies of 2013.” 3
At the time of the FDA clearance of this technology, I was working for a large, full-service provider for clinical laboratory and anatomic pathology services in southern Florida. We served as the core lab for 13 hospitals, providing all routine microbiology testing for them as well as specialty testing for hospitals throughout Florida.
Our lab director was quick to acquire MALDI-TOF MS because we were eager to adopt technology that would reduce the turnaround-time of our results. We immediately realized several key benefits from MALDI-TOF MS. While mass spec-based methods for pathogen identification still require culture, MALDI-TOF can effectively identify a pathogen from significantly less culture growth compared to standard biochemical methods, which require clearly developed and well distinguished colony development.4 MALDI-TOF MS can often make an accurate identification based on the first signs of growth.
This is vitally important and a key benefit of MALDI-TOF that leads to multiple other advantages. Most bacterial organisms begin to grow at 18 to 24 hours, but it can be another day, if not 48 hours or more, before sufficient isolated growth is seen to perform biochemical identification. Because of this, we immediately cut our identification times by six hours to several days. At the first signs of culture growth, we would run the isolate on MALDI-TOF MS, and we had a positive identification within minutes.
The benefits of rapid infection identification are well documented. When clinicians can intervene quickly with optimal antimicrobial therapy, patients recover faster and have reduced length of hospital stay, and hospitals can save dramatically on pharmacy expenditures. Our clinicians noticed this almost immediately after adopting MALDI-TOF MS.
Of course, positive identification is just one part of the puzzle. Rapid identification also provides very useful information regarding pathogens with intrinsic resistance.
Anaerobic organisms provide an excellent example of this benefit. Anaerobes are high-maintenance pathogens that require a much more manual and time-intensive process to get a positive identification. They must be protected from oxygen exposure and typically need at least 48 hours of oxygen-free incubation to see visible growth. However, because of poor methodology during specimen collection, transportation, and preparation for anaerobic culture, delayed identification of anaerobes and the need for a second sample collection and repeated culture are not uncommon. The delays prolong proper treatment and can contribute to the deterioration of a patient’s condition.
One example is Bacteroides, an anaerobic gram-negative bacilli. Bacteroides species are a common cause of infections that can develop in all body sites including the central nervous system, head, neck, and abdomen, as well as skin and soft tissue infections. They are often difficult to isolate and identify, and treatment is complicated by the slow growth of the organism and the increasing resistance to antimicrobial agents.
One member of the Bacteroides family, B. fragilis group, includes several species including B. fragilis, which is the cause of many clinical infections. The bacteria in this group are resistant to penicillins, usually through the production of beta lactamase.
When an organism such as Bacteroides can be rapidly identified, this provides physicians with information they can use—along with antibiogram data and patient assessment—to make treatment decisions. We found that for certain organisms, especially anaerobes, we could provide physicians with useable data before the susceptibility results were available.
Of course, having a positive identification is critical to selecting the right susceptibility test. So by generating results quickly from colony growth, MALDI-TOF MS also helps in speeding the process of antimicrobial susceptibility testing by guiding the laboratorian to choose the correct susceptibility testing to perform.
Another benefit was that with only two reagents, a pipette tip and a MS slide, MALDI-TOF MS significantly reduces the use of the reagents required and waste generated compared to routine biochemical identification.
For the core lab I worked at, MALDI-TOF MS was an ideal tool that provided many benefits, improved our workflow, and provided clinicians with faster results. For this reason, a growing number of labs are investing in this technology.
Microbiology is never black and white, but when you can provide positive pathogen identifications after only 18 to 24 hours—even if the culture is mixed—the benefits to the lab, clinicians and patients are significant.
REFERENCES
- Beall A, Automated mass spectrometry. MLO. 2013;45(10):50-51. https://www.mlo-online.com/automated-mass-spectrometry.php.
- U.S. Food and Drug Administration. New test system identifies 193 different yeasts and bacteria known to cause illness. Aug. 21, 2013; www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm365907.htm.
- MedCity New. Bariatric surgery for diabetes deemed Cleveland Clinic’s top medical innovation for 2013. Oct 31, 2012. http://medcitynews.com/2012/10/cleveland-clinic-deems-bariatric-surgery-for-diabetes-the-top-medical-innovation-for-2013/
[Mass spec was #3 of 10.] - Wunschel DS, Hill EA, McLean JS, et al. Effects of varied pH, growth rate and temperature using controlled fermentation and batch culture on matrix assisted laser desorption/ionization whole cell protein fingerprints. J Microbiol Methods. 2005;62(3):259-271.
Mary Valdez, MS, MT, serves as product manager of ID/AST Systems at bioMerieux. Inc. She joined the company in early 2016 after spending 16 years as a Section Coordinator in the Microbiology Lab at Integrated Regional Laboratories in Fort Lauderdale, FL.
