Helping clinicians quickly and effectively address the medical concerns of their patients should be the ultimate goal of any clinical laboratory. Delivering on this goal can be especially important when a patient presents with a bacterial or fungal infection. These infections, ranging from methicillin resistant Staphylococcus aureus (MRSA) cellulitis to Gram-negative sepsis, can manifest rapidly, causing significant disease and even death within hours. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF) is being embraced by laboratories primarily in clinical microbiology because it is a fast, accurate, and cost-effective method for identifying bacteria, fungi, and other infectious agents isolated from culture, based on automated analysis of the mass distribution of bacterial proteins. Because of its accuracy and speed, MALDI-ToF can help improve patient outcomes by speeding diagnosis and improving the quality of care.
There is a growing recognition within the lab industry that MALDI-ToF may be a transformative technology, one with the potential to replace conventional lab equipment and processes. However, many smaller and even some large commercial laboratories have not adopted it yet as an exclusive or primary means for identification of bacteria, yeast, and mycobacteria. Many industry leaders believe this is a missed opportunity.
Benefits and limitations
There are many benefits to incorporating MALDI-ToF to aid in identification of microorganisms. Identification with MALDI-ToF is a relatively simple process. Once a slide has been prepared, it is introduced into a high-vacuum environment, where the sample is ionized with a laser burst that releases proteins. These proteins are then accelerated using an electric charge, and the time of flight is recorded. (Lighter proteins travel faster, while heavier proteins travel more slowly.) At the end of travel, the proteins are detected with a sensor.
The sensor then creates a spectrum representing the protein makeup for each sample. Identification is made when the spectrum from a sample is compared against a large database of spectra of characterized bacteria, yeast, and mycobacteria. The process can reduce the time needed for identification and diagnosis from days to hours.
There are, however, some limitations to MALDI-ToF. Some organisms may require repeat analysis and additional processing, and some closely related organisms are not differentiated and may cause challenges with identification. The technique also is generally not useful for direct testing of clinical specimens. Finally, the initial purchase price of the equipment is high, which may limit the types of labs that can adopt it.
The easiest way to see the value of MALDI-ToF for patient care is to think of it in terms of specific life-threatening infections where the time from initial infection, to diagnosis, to treatment is highly correlated to patient morbidity. Sepsis is a life-threatening condition that presents itself as a fever, increased heart rate and breathing, and pneumonia-like symptoms.
These symptoms can be confused with other conditions, which may delay diagnosis and care. Sepsis is typically treated with intravenous fluids and broad-spectrum antibiotics. Antibiotics are given as soon as possible to avoid septic shock and death. However, delayed diagnosis can delay care, worsening patient outcomes.
Insights from studies
Researchers have been increasingly addressing the value of MALDI-ToF. Delport et al specifically addressed the use of MALDI-ToF for the diagnosis of sepsis. The investigators found that MALDI-ToF identification significantly decreased the amount of time to identify a specific pathogen, and a short incubation MALDI-ToF identification protocol from positive blood cultures further reduced time to identification by 38.78 hours overall. The study also noted that changes needed to optimize antibiotic therapy in the study population occurred 20.2 hours earlier when MADLI-ToF was used to aid diagnosis, as compared to conventional test methods. Wrote the authors: “The earlier initiation of antibiotics certainly contributed to the overall improvement in outcomes in patients with sepsis and bacteremia.”1 In another study, Tan et al also found that the MALDI protocol yielded results more quickly than the standard protocol for most isolates when assessed by organism groups, leading to better patient outcomes.2
In addition to bettering patient outcomes through earlier diagnosis, MALDI-ToF technology may have future applications in predicting antibiotic resistance. For instance, a third recent study demonstrated that MALDI-ToF can detect the presence of carbapenemases, a type of enzyme which promotes drug resistance to standard antibiotics. This technique, which can identify drug resistance in hours, could help physicians determine which antibiotic to prescribe.3 This future benefit may be of consideration for some laboratories.
Taking the long view
After weighing the benefits and limitations of MALFI-ToF, an increasing number of commercial laboratories will likely be making efforts to incorporate it as their primary means for identification of bacteria, yeast, and mycobacteria. When they do, they will not simply be inserting another piece of equipment into their existing workflow, which could actually slow the process and increase labor; rather, they will be designing a new workflow to optimize the technology and ensure that results get from the lab to clinicians and patients quickly.
While not all laboratories are capable of widely adopting MALDI-ToF, those that can, probably should. MALDI-ToF may promote better patient outcomes through speedier diagnosis and information to influence efficacious treatment for many bacterial, yeast, and mycobacterial infections—greatly improving the quality of clinical management and patient care.
REFERENCES
- Delport JA, Strikwerda A, Armstrong A, Schaus D, John M. Quality of care is improved by rapid short incubation MALDI-ToF identification from blood cultures as measured by reduced length of stay and patient outcomes as part of a multi-disciplinary approach to bacteremia in pediatric patients. PLoS One. 2016;11(8): e0160618.
- Tan KE, Ellis BC, Lee R, Stamper PD, Zhang SX, Carroll KC. Prospective evaluation of a matrix-assisted laser desorption ionization–time of flight mass spectrometry system in a hospital clinical microbiology laboratory for identification of bacteria and yeasts: a bench-by-bench study for assessing the impact on time to identification and cost-effectiveness. J Clin Microbiol. 2012;50(10):3301-3308.
- Hrabák J. Detection of carbapenemases using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) meropenem hydrolysis assay. Methods Mol Biol. 2015;1237:91-96.
Janet Cromien serves as Director, National Laboratory Operations, Microbiology, for Quest Diagnostics.
Dale Schwab, PhD, serves as Senior Scientific Director, Infectious Disease, for Quest Diagnostics Nichols Institute.
