Syndromic testing panels have become an important tool in clinical testing and patient care. They allow clinical microbiology laboratories to quickly identify bacteria, viruses, fungi, and parasites, which can help patients get the right treatment quickly. These tests can also cut down on unnecessary antibiotic prescribing when it won't help patients and might contribute to antibiotic resistance.
These panels seek to balance the benefits and complexity of the molecular diagnostics revolution in microbiology. While real-time PCR targeting single-analyte or small panels offers exquisite speed and sensitivity compared to traditional culture, it still has its limitations: the approach initially required clinicians to request which pathogens they were looking for, rather than only the specimen’s origin (1). Syndromic panels solve the tradeoff with a preset list of organisms for molecular interrogation.
However, just like in chemistry or any other clinical laboratory discipline, robust laboratory stewardship is essential. The overuse of these panels can lead to higher costs for healthcare systems and patients, and sometimes lead to confusing results when not correctly interpreted in the context of the patient—or when used on the wrong patient entirely.
We spoke to Jennifer Dien Bard, PhD, Director of the Clinical Microbiology and Virology Laboratory at Children’s Hospital Los Angeles and Professor of Pathology at Keck School of Medicine of USC about the future of syndromic testing panels and how if implemented thoughtfully and interpreted carefully, they have the potential to improve patient care.
This interview has been edited for space and clarity.
How is syndromic molecular testing improving patient care versus more traditional approaches?
Syndromic testing allows the laboratory to detect a number of different pathogens all at the same time, and it allows you to do that in a very fast way—typically within an hour or so.
Let’s say, for example, the patient presents with respiratory symptoms. A variety of organisms can cause that infection. Syndromic molecular testing allows a provider not to have to think about each potential pathogen that a patient may be infected with. The hope is that they can react to it quickly, whether it be withholding or initiating antimicrobials when necessary.
These benefits have the potential to encourage overuse. How do you address that?
Because these tests are so readily available and so easy to test, there is the risk of over-testing, particularly in patients that may not fit the criteria for that test.
Unfortunately, over-testing dilutes the positive effect that these tests can have. When you’re doing studies and pulling results of all the patients you’re testing, if there’s a subset of patients who shouldn’t have been tested, it affects results.
It’s also important to note that some insurance companies have very defined criteria as to the patient population for these tests, and who they’ll reimburse for.
If you’re comparing traditional culture to a multiplex syndromic panel, of course the cost of the test would be a lot more than it would be for just a culture. That costs the healthcare system, which may then charge patients for a portion of that test that they’re not being reimbursed for. Over-testing raises costs all around.
But the potential for over-testing is not unique to syndromic testing.
It’s pretty much an issue with any laboratory test and why stewardship is so important. Clinicians need to order the right tests at the right time and for the right patients only.
Leaving COVID-19 aside for the moment, let’s say if you have a patient that doesn’t have any respiratory symptoms. If you choose to test them with a respiratory panel anyway and find they’re positive for rhinovirus/enterovirus, the clinician then has to decide, do I need to isolate this patient? What’s the cost of care related to that?
Finding results like this from inappropriate testing can distract clinicians from further pursuing an actual diagnosis. They might focus on that rhinovirus and enterovirus result while there is something else wrong with that patient. The test can potentially point clinicians in the wrong direction and prevent them from exploring the real reason behind the patient’s health problems.
How can laboratory stewardship optimize testing and improve care?
There are things we can do to prevent overuse of syndromic panels, such as placing automatic testing restrictions. For example, if you have a patient who is tested using a syndromic respiratory panel, the likelihood of the same patient needing to be tested again within 7, 10, or 14 days is very low. Repeat testing hasn’t been found to be helpful. Other options would be to require an infectious disease consult prior to approving specific test orders.
Education is always a huge piece of this. It’s communicating with providers so that they understand what the test actually is, how it works, and the answers it can potentially provide. This is where clinical microbiologists are important, and why we work so closely with physicians, antimicrobial stewardship teams, and infectious diseases teams. We are available for consults as part of clinical services and can guide clinicians on the utility of a test.
It shouldn’t be assumed or expected that clinicians are going to understand the ins and outs of every single laboratory test. That’s why offering continuing education and consult services that explain specifically what test are for, the potential limitations, and how to interpret the results can help guide the management of patients.
How should molecular laboratories approach choices about syndromic testing versus more targeted molecular testing?
I think a big part is going to be the patient population and what their needs are. We also need to factor in available staffing. Laboratories at many community hospitals often don’t really have the staff to perform high complexity PCR testing. Instead, syndromic testing allows them to offer more complete molecular testing, where they may not have capability otherwise.
In our laboratory, we have the capacity and infrastructure to perform moderately complexed syndromic testing as well as high complexity molecular tests. We therefore decide which test to use based on the needs of the patient population, workflow, and how a particular test would be implemented as part of a routine workup in our lab.
For example, let’s look at the meningitis panel. We felt it was important enough—and such a critical disease that affects our pediatric patient population—that we implemented the syndromic panel at a 24/7 approach. That’s better for our pediatric patient population than waiting for single-target PCR that would take a couple of days to get back.
What do you think we’ll see in the future when it comes to syndromic testing?
There likely will be more syndromic testing for other conditions—possibly urinary tract infections, maybe pharyngitis causing bacteria and viruses.
I can also see increased testing in communities as more of a point-of-care type of approach. You could get a panel done right at a physicians’ office, which could stop a provider from prescribing an antibiotic for a viral illness. However, this is also where emphasis on diagnostic stewardship would be critical.
How has COVID-19 affected how we think about syndromic testing?
It’s allowed us to move forward with home testing, which wasn’t really a thing before COVID-19. COVID1-19 has a unique presentation, where patients can be asymptomatic or severely ill. Usually for other viruses, you’re going to be symptomatic.
But COVID-19 has allowed us to think outside the box when it comes to testing. Just consider saliva testing, which is not something you would normally think about as a matrix for respiratory infections. But we have found with COVID-19 that it actually works quite well.
What else do you want our readers to know on this topic?
I think it’s important to emphasize that syndromic testing must be part of a multidisciplinary approach. That means relying on laboratory experts to guide both utilization and interpretation of results. Because these test systems are so easy to use, that can easily forgotten or underestimated.
It’s critical we have these laboratory experts guiding clinicians in the nuances of how we can best use this technology. As we get into more highly complicated types of molecular testing, that’s going to be even more critical.
References
1. Miller MB. Opinion on syndromic panel-based testing in clinical microbiology. Clin Chem 2020;66:42-4.
2. Bard JD and McElvania E. Panels and syndromic testing in clinical microbiology. Clin Lab Med 2020;40:393-420.