As the antimicrobial resistance (AMR) crisis grows, bacterial infections are becoming harder to treat. Chris Lock, vice president of R&D at the mass spectrometry specialist SCIEX, discusses how rapid diagnostics can help doctors wield antimicrobial treatments more effectively.
The AMR crisis is growing increasingly severe, resulting in superbugs that are able to shrug off multiple antibiotics. According to the World Health Organization, drug-resistant microbes killed 1.27 million people around the world in 2019, and contributed to the deaths of another 3.68 million. One stark example is methicillin-resistant Staphylococus aureus (MRSA), which killed more than 100,000 people in 2019.
In addition to novel drugs, one of the best weapons to combat AMR is rapid diagnostics. This concept is the focus of many biotech companies, with one recent example being a team-up of Boehringer Ingelheim, Evotec and bioMérieux.
Another prominent player in diagnostics is SCIEX, which develops and supplies analytical technologies including mass spectrometry and liquid chromatography.
SCIEX’s vice president of R&D, Chris Lock, has spent 18 years with the company and leads a global team developing workflows for analytical techniques. He explained to us how important diagnostics is for tackling AMR, and how SCIEX and collaborators are working on a rapid technique to detect the pathogens causing infection.
Why are effective diagnostic techniques essential for tackling AMR?
Chris Lock (CL): When a patient requires treatment for an infection with an antimicrobial agent, time is of the essence. Unfortunately, identifying the bacterial species causing an illness can take a while and determining a particular pathogen’s susceptibility and resistance to specific antibiotics takes even longer. As a result, many physicians must start treatment without knowing all the details of their patient’s infection.
Physicians often begin by prescribing broad-spectrum antibiotics that are effective against a wide range of bacteria, then later switch to narrower-spectrum agents. Around half of patients are started on the wrong antibiotic and without proper identification of the strain and species of the infection-causing bacteria.
While this practice can be — and is — lifesaving, it also fuels the development of multidrug-resistant bacteria. That’s why the world desperately needs fast, affordable strategies and workflows — including antimicrobial susceptibility testing — to identify and characterize bacterial infections.
What are the main obstacles to getting a rapid diagnosis of a bacterial infection?
CL: The accurate identification of the bacteria causing a patient’s infection requires blood and other samples from which cultures of the bacteria are grown. Collecting these samples is a long and laborious process.
The identification of bacteria from blood cultures can be made even more challenging if an insufficient amount of blood is collected from the patient or if the patient has already taken an antibiotic. In addition, delays can occur with laboratory processing or transportation, especially if the laboratory facilities are located somewhere other than the hospital or sample collection site, and contamination can be a frequent problem during blood culture collection.
Many bacteria can also be very finicky and difficult to culture in standard automated systems. And even with automated systems, highly trained and skilled human operators are needed to interpret results and identify the bacteria.
These issues can delay the identification of the bacteria by several days. Even rapid antimicrobial susceptibility testing methods, which can be performed after or at the same time as bacterial identification, can still take several hours or be delayed by several days.
Can you explain how SCIEX is developing a way to overcome these challenges?
CL: Instead of waiting for a bacterium to grow in culture, a process that can take days or even weeks, researchers have begun turning to alternative strategies that can identify and characterize bacteria in hours.
In recent years, mass spectrometry has emerged as a gold standard tool in clinical microbiology. The technique works by identifying various chemical compounds within a sample. Each chemical found yields a unique spectrum of peaks, which researchers can compare to a database of known samples in order to identify the chemicals. Since different types of bacteria have a different chemical fingerprint, researchers can rapidly identify the organism causing an infection.
Mass spectrometry by itself is powerful, but researchers can increase the sensitivity of the technique by using liquid chromatography to isolate specific types of compounds before performing mass spectrometry.
Scientists from SCIEX, along with professors Jerome Lemoine of the Institute of Analytical Sciences in Lyon, France, and François Vandenesch of the Hospices Civils de Lyon, Hôpital de la Croix Rousse, have developed a way to increase the range of molecules you can detect in a single mass spectrometry and liquid chromatography run.
The method, called stMRM (scout-triggered MRM), uses marker molecules, or “scouts,” to more easily track different molecules in a sample. It has proved so useful for multiple applications that SCIEX has incorporated the stMRM algorithm into its SCIEX OS software.
While their assays are not yet ready for clinical application, Lemoine and Vandenesch’s stMRM method can already analyze 300 hallmark peptides in pathogens that cause sepsis in eight minutes.
How do you see the field of proteomics developing over the coming years, and what impact might this have on the threat of antimicrobial resistance?
CL: Proteomics is a rapidly expanding field of research with an ever-growing range of applications. The technology is rapidly advancing to keep pace with the analyses researchers want to perform in their experiments. We’re seeing more combinations of proteomics with other kinds of omics (such as metabolomics) and other novel analytical approaches (such as single-cell gene expressions) to provide a clearer picture of what is happening in biology and disease.
With millions of people dying each year from AMR and the problem only projected to get worse, these are the kinds of technologies we need to slow the development of AMR. They hold great promise for leading to better diagnostics that will enable more accurate treatments for infections and a more effective antimicrobial stewardship.