Antimicrobial resistance continues to be a worldwide problem. Antimicrobial resistance was associated with nearly 5 million deaths in 2019, according to a study published in The Lancet (2022; doi: 10.1016/S0140-6736(21)02724-0).
In the U.S. alone, more than 2.8 million antimicrobial-resistant infections happen each year, and more than 35,000 people die as a result, according to the Centers for Disease Control and Prevention’s (CDC) most recent Antibiotic Resistance Threats Report (2019; doi: 10.15620/cdc:82532).
Antimicrobial resistance is an expensive problem, too. The CDC also found that infections caused by multidrug-resistant organisms contribute more than $4.6 billion to healthcare costs annually (Clin Infect Dis 2021; doi: 10.1093/cid/ciaa1581).
Clinical laboratories have always played a part in combating antimicrobial resistance by diagnosing what is making patients sick and what kinds of antibiotics have the best chance of working against a particular organism.
This role in the clinical care team has become more solidified due to a 2019 mandate from Centers for Medicare and Medicaid Services that acute-care hospitals that serve Medicare or Medicaid patients develop and implement antibiotic stewardship programs.
We spoke to Thomas J. Kirn, MD, PhD, Associate Professor of Pathology and Laboratory Medicine and Medicine at the Robert Wood Johnson Medical School in New Brunswick, New Jersey, about the role clinical laboratories play in combating antimicrobial resistance, how advances in both engineering and laboratory technology have changed the approach clinical laboratorians take in this fight, and how that may change in the future.
This interview has been edited for space and clarity.
How has the role of the laboratory changed in managing the challenge of antimicrobial resistance?
We in the laboratory have always played a key role in antibiotic stewardship. It starts with things as simple as antibiotic cascading, reporting the most narrow-spectrum antimicrobial agents, then expanding them once you run into resistance problems.
With the formation of what are now mandated antimicrobial stewardship teams, clinical laboratories are even more involved in antibiotic choices. There’s now an outward facing arm of the laboratory in the healthcare system that has direct interaction with clinicians.
How has the technology changed?
In the last 15 years we’ve seen the advent of rapid diagnostic tests. Many of them are molecular, with some phenotypic. Rapid tests allow us to predict antibiotic susceptibility before conventional susceptibility results are available, usually within a few hours of isolating the organism.
A couple of technologies have fed into that, including MALDI-TOF, which combines matrix-assisted laser desorption/ionization with time-of-flight mass spectrology to rapidly identify organisms. Many laboratories have transitioned from traditional biochemistry techniques to identifying organisms through MALDI-TOF — and for good reason. It shrinks the time from getting an organism isolated and performing an identification from a day or two to a few hours.
With some organisms, the susceptibly profile is rather predictable based on the identification. For example, if you isolate a Group A streptococcus, you know it’s highly likely to be susceptible to penicillin. For other organisms, like for Staphylococcus aureus, which is one of our bigger problems, you don’t know whether it’s susceptible to methicillin. You need some more information. That’s where molecular and/or rapid phenotypic tests
How have clinical laboratories used advances to affect patient care when it comes to antibiotic prescribing?
Trying to implement these technologies seamlessly into patient care has been a challenge. For example, in our institution we were able to get the time for reporting results on blood cultures down from 36 hours to two hours using rapid tests. We were getting the results out there, but the time for getting someone to acknowledge these results and use them in patient care? It was still 36 hours. Clinicians weren’t ready to receive and act on the information.
This shows why it’s critical to have a line of communication to clinicians to make sure they know what the laboratory is offering and can do the right thing with the information.
Working collaboratively with our antimicrobial stewardship program and our pharmacy team we were able to significantly improve the timeframe in which antibiotic changes were made. It was a combined effort that changed antibiotic usage in our institution.
This example shows how the technology came first, but the next step was just as critical: Understanding how to make sure clinicians were doing what you expected them to do with that information.
At our institution, we started with mecA and staphylococcus aureus. After a year, people got comfortable with it, and then we went onto the next thing, and the next thing, and the next, adding new tests to the menu.
How is molecular technology changing the ways laboratories work?
I don’t think it is about creating something disruptive in the field. Instead, it has been a steady progression.
When I was in college, we were learning how to perform PCR-based tests that didn’t make it into clinical laboratories until a decade later. Before we could use these kinds of technologies, we had to make sure testing could be performed in a clinical laboratory where not everybody is necessarily a molecular biologist.
That’s where engineering advances have moved us forward, designing high throughput instruments with simple workflows.
Do you see any advances in testing on the horizon, or do you expect to see more innovation on the engineering side?
It’s hard to say. I never would discount the idea that some brilliant person will come up with something really clever. But for at least the last 15 years, it’s been incremental advances along the same lines, and I expect that to continue for the next 5 to 10 years.
I do think that whole genome sequencing and next-generation sequencing will potentially give us new tools, and we’ll probably see some of that make its way into mainstream laboratories. It’s not standard of care in most places right now. But being able to understand and sequence an organism’s entire genome, and use that to predict its antibiotic susceptibility, could be enormously powerful.
The question is, can we get results quickly enough? And is understanding the genetic makeup of an organism going to allow laboratories to reliably predict its in vitro susceptibility profile and be useful for patient care? For some organisms, it works great. For others, it’s a little less predictive.
What’s next for clinical laboratorians when it comes to antimicrobial resistance?
More people in medicine are now aware of the laboratory’s contribution, which helps. It used to be that the laboratory would go to the administration to ask for support every time it saw an opportunity to implement a new technology or program that could positively impact patient care. Now, through our antimicrobial stewardship program, it’s a group effort. In fact, it is sometime a pull from the clinical side rather than a push from the laboratory.
Technology advances are a good thing, but then the interpretation gets a little bit more difficult. For next-generation sequencing, for example, it might be like in traditional molecular diagnostics, where the laboratory director or an attending pathologist reviews results as they go out. These results are complex and need to be explained.
It’s possible that this will extend to microbiology as well, as we see more complex data coming out related to individual organisms. Because when we start to get more of this data, it will likely need to be interpreted in a way that is similar to complex genetic tests.