By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN;
Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

SYNOPSIS: In the United States, rapid diagnostic testing for panels of potential gastrointestinal pathogens in children increases the yield of identifying rare pathogens, but, overall, does not change length of stay for hospitalized patients or reduce hospital charges.

SOURCE: Cotter JM, Thomas J, Birkholz M, et al. Clinical impact of a diagnostic gastrointestinal panel in children. Pediatrics 2021;147:e2020036954.

Globally, diarrheal disease is the second leading cause of preschool-age mortality. In the United States alone, hundreds of millions of dollars are spent each year to manage children with gastroenteritis. Nonetheless, most episodes of diarrhea in children resolve spontaneously with adequate hydration and do not require specific etiology-directed treatment. Thus, early diagnosis of severe, treatable, and potentially lethal causes of diarrhea would be helpful both to target helpful disease-limiting therapies appropriately and to avoid inappropriate use of unhelpful antimicrobial agents.

During the past several years, advances in molecular diagnosis of pathogens have prompted the development of test panels that rapidly identify the presence/absence of dozens of pathogens (including viruses, bacteria, and parasites) in stool samples. At the same time, though, there have been questions about the value of these relatively expensive tests in clinical practice. Now, Cotter and colleagues provide data about the clinical utility of these panels, as compared to traditional stool testing, in identifying pathogens, and about the effect of this testing in altering patient outcomes in a large population of children.

Using results of stool tests done in the Children’s Hospital Colorado microbiology laboratory from 2013 through 2017, Cotter and colleagues compared data from 24 months prior to the adoption of gastrointestinal pathogen test panels with data from one to three years after the availability of these tests in children younger than 19 years of age. (The first year of initial panel test availability was not included in the analysis since practices were transitioning at that time.) Samples came from inpatient and outpatient settings affiliated with an academic children’s hospital and with three community children’s hospitals. The panel used in that setting included tests for 22 different gastrointestinal pathogens.

Testing was done only on non-formed stool. Decisions to use the testing were made by clinicians and were not affected by the investigators. However, to avoid providing clinicians with “too much information” that might prompt inappropriate practice, the laboratory did not routinely report results of enteropathogenic, enteroaggregative, and enterotoxigenic E. coli (because of the uncertain clinical significance of these “pathogens” in the United States) or of Clostridioides difficile during the first year of life (because this usually represents asymptomatic colonization at this age).

A total of 12,222 stool tests were included in the study, representing 8,720 medical encounters by 6,733 individual patients. Overall, 40% of patients had a complex chronic medical condition pre-dating the acute diarrhea illness, and 60% of patients were hospitalized at the time of testing. Stool testing, per patient population size, increased by 21% during the final years of the study. More patients underwent multiple different stool tests during the era prior to panel testing (after which it became more common to do only the panel of tests).

During the two years of panel testing, stool tests were more likely to be positive (40%, as compared to 11% during the years prior to panel testing). Prior to panel testing, C. difficile, Salmonella, Campylobacter, Shiga toxin-producing E. coli, and Giardia were the most commonly identified pathogens. Norovirus, sapovirus, rotavirus, and adenovirus were identified more commonly with the pathogen panel testing than before. With the panel testing, 9% of patients had multiple pathogens identified concurrently. Of those with a positive panel test, 54% had a virus, 38% had C. difficile, 18% had other bacteria, and 5% had a parasite.

Panel test results were available to clinicians more quickly than were the previous conventional test results (four vs. 31 hours). With the panel, but not including C. difficile-positive patients for this analysis, antimicrobial therapy was given based on results for 3.7% of children, as compared to 1.9% with previous conventional testing.

For hospitalized children who received antimicrobial treatment based on test results, the length of stay in the hospital was shorter during the panel testing era (three vs. five days). Overall for the entire cohort of patients, though, the length of stay was not different during the pre-panel and post-panel eras. With shorter stays, the overall hospital charges were less for those with focused bacterial or parasitic treatment than for those without such treatment, but the hospital charges, overall, were not different based on the type of testing done.

The authors rightly concluded that focused gastrointestinal pathogen panel testing yielded more diagnostic information more quickly than did previous testing, and panel testing helped identify more children who could benefit from focused antimicrobial treatment. However, the beneficiaries of such gains represented only about 2% of the patients tested. The authors recommended that these new diagnostic tests be used judiciously, since many tests were done in generally healthy children without severe gastrointestinal disease who had low pre-test probability of requiring etiology-focused therapy.

The authors also wisely noted that the problem of unnecessary “low value” use of pathogen panels is seen when testing for central nervous system and respiratory pathogens as well. These still-new pathogen panels offer added value when used judiciously for children with high clinical suspicion of finding a treatable pathogen.

COMMENTARY

In an editorial accompanying the paper by Cotter and colleagues, Tarr and Tarr concluded that molecular enteric microbiology testing is “a model opportunity for diagnostic stewardship to maximize worth and minimize wasteful expense.”1 They noted that panel testing has been shown in other adult and pediatric settings to reduce unnecessary antibiotic prescriptions and, in the case of viruses being identified, to reduce unnecessary pursuit of additional tests and diagnoses.1

Cotter and colleagues cleverly modeled judicious use of test results by choosing not to report findings that might prompt inappropriate treatment — infections with some E. coli that neither require nor are altered by antimicrobial therapy and C. difficile in infants (who, by lacking the toxin receptor or other reasons, seem not to become symptomatic with C. difficile colonization). Whether by decree of the laboratory or by education of clinicians, efforts should be made to prevent “positive” findings of test panels from triggering unhelpful treatment.

So, which children are most likely to benefit from gastrointestinal pathogen panel testing? Results are most likely to helpfully alter treatment for children with acute grossly bloody diarrhea and those whose illness includes severe abdominal pain and/or high fever.1

We face similar concerns while dealing with patients with lower respiratory tract infections. In that setting, care could be altered with rapid access to tests identifying influenza (for which specific medication might be indicated) and respiratory syncytial virus (which might prompt fewer radiographs looking for evidence of bacterial pneumonia).2 However, knowledge about the presence or absence of other viral pathogens might not alter treatment decisions. Observational studies can document potential benefits of such testing, but “real world” cost effectiveness data are necessary to determine which patients in which settings actually should undergo such testing.2 

REFERENCES

  1. Tarr GAM, Tarr PI. Pediatric enteric diagnostic stewardship: The right test in the right context. Pediatrics 2021;147:e2020044941.
  2. Pinsky BA, Hayden RT. Cost-effective respiratory virus testing. J Clin Microbiol 2019;57:e00373-19.