Editorial Article: Syndromic testing: Achieving better clinical outcomes for gastrointestinal pediatric patients

Dr. Samuel Dominguez shares the importance of robust testing methods and diagnostic stewardship

11 Jun 2021



Dr. Samuel Dominguez, Children’s Hospital Colorado

In this exclusive interview, we speak with Dr. Samuel Dominguez, pediatric infectious disease physician and the medical director of the clinical microbiology laboratory at Children’s Hospital Colorado, about the current challenges with traditional gastrointestinal (GI) testing and his latest research into identifying patients that will benefit most from syndromic panel testing.

What role do diagnostics play when it comes to the gastrointestinal system?

SD: Fortunately, for most pediatric patients, acute gastroenteritis is a short, self-limiting illness that usually does not require treatment aside from supportive care. For these patients, diagnosing the cause of their gastroenteritis is not usually needed. 

However, diagnostics are important in ruling in or out a pathogen that requires treatment. This includes children at high risk of more serious diseases due to a bacterial or parasitic pathogen (particularly young children or those with a predisposing high-risk or immunocompromising condition) or diagnosis of a pathogen that would be treated regardless of the patient’s risk factor (such as C. difficile or Giardia). 

Some providers use GI testing to ‘rule out’ a serious GI infection. Although testing can never fully rule this out as we don’t test for everyone possible pathogen, this can be helpful in some scenarios. For example, a child with a history of inflammatory bowel disease might present with new-onset bloody diarrhea and testing for GI pathogens might help determine if this is due to the acquisition of a new infection versus a flare of their underlying condition.  

Diagnosing a GI pathogen can also be extremely helpful for epidemiologic purposes to identify the cause of an outbreak, find an etiology in a complicated patient that might prevent further testing or, less commonly, to find an etiology to reassure patients that this should be a self-limited disease. 

What are the current challenges associated with traditional testing? 

SD: Conventional or traditional testing usually involves a battery of tests, including standard stool bacterial culture, pathogen-specific assays, electron microscopy (though not commonly used), and ova and parasite microscopy exam. There are a variety of pathogen-specific assays available, and they could be antigen-based or nucleic-acid-based (PCR). The most commonly used in clinical practice are norovirus PCR, Giardia and cryptosporidium DFAs, and a number of different tests for detection of C. difficile.  

Testing for C. difficile is particularly challenging in pediatric patients because of the high rate of colonization, particularly in children under one year of age. Additionally, what role E. coli pathotypes play in disease in high-income countries is not fully understood.

Other challenges with traditional testing include:

  • Long turnaround times
  • Labor intensiveness
  • Poor sensitivity
  • Required expertise (particularly for ova and parasite exams)
  • Possible complex and confusing ordering strategies
  • Multiple tests add expenses 
  • Different etiologies of infectious gastroenteritis have similar clinical presentations

What impact does successful testing have on patients, particularly children?

SD: For normal healthy children, this is somewhat of a complicated question and we tried to answer this in our recently published study1. Ideally, testing would help to limit inappropriate treatment, get patients on appropriate treatment quicker, and improve overall clinical outcomes, including shorter hospital stays, decreased ancillary testing, etc.

Results are most impactful where a treatable pathogen is detected. In enabling the rapid prescription of appropriate therapy, patients would presumably improve in a much shorter period of time. Testing is also impactful in those who are immunocompromised or who have underlying gastrointestinal disease, as this helps decide if their symptoms are due to an infection or another cause.

Some institutions also use testing to help inform infection control practices through the isolation of patients. We use testing to help inform these decisions too, but we primarily isolate children in the hospital based on their symptoms and so testing doesn’t have as big of an impact.  

What are the advantages, in and out of the laboratory, of a syndromic molecular GI panel?  

The BioFire® FilmArray® GI Panel is a rapid PCR test that identifies 22 of the most common pathogens associated with gastroenteritis - including 13 bacteria, five viruses, and four parasites - all from one patient sample, with results available in about one hour.

SD: The overall promise of syndromic testing, offered by solutions such as the BioFire® FilmArray® Gastrointestinal (GI) Panel, is comprehensive testing, but it also offers greatly improved turnaround times, increased sensitivity, increased pathogen detection, and simplified ordering strategies, which are all designed to hopefully lead to better clinical outcomes. The resultant streamlined workflow also has a huge impact on lab efficiency. 

However, there are also considerations to take into account due to the variability in the presentation and action of different microorganisms. It can be difficult to differentiate colonization or asymptomatic carriage from the true cause of symptoms and some pathogens are shed for a longer period of time, so what you are detecting now may have been from a previous infection and not the current cause of a patient’s symptoms. There are also downstream concerns including the identification of misleading causes and the overtreatment of pathogens of unclear significance. 

What do you see for the future of GI testing?  

SD: The biggest challenge currently is diagnostic stewardship – trying to understand and identify which groups of patients will benefit most from syndromic panel testing and then implementing ordering strategies to target these patients – an issue we discussed in a recent publication2

I think there is also a movement to be able to ‘pick and choose’ from a menu and only test for the pathogens you want to. On some level, this defeats the purpose of some of the advantages of syndromic testing but addresses some of the concerns around over-testing, for example, we have taken this approach at our hospital and providers can now order a gastrointestinal pathogen panel with and without C. difficile.  

References

  1. Cotter JM et. al. Clinical Impact of a Diagnostic Gastrointestinal Panel in Children. American Academy of Pediatrics. 2021
  2. Cotter JM et. al.  Impact of Multiplex Testing on the Identification of Pediatric Clostridiodes Difficile. The Journal of Pediatrics. 2021

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