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: Availability of molecular testing panel results that were positive for Salmonella in children led to increased hospital admissions, increased subsequent microbiologic testing, and increased antibiotic use — all without benefit to patients.
SOURCE: O’Boyle H, Kirpalani A, Weiss L, et al. Management and outcomes of Salmonella gastroenteritis in the era of rapid molecular testing. Hosp Pediatr 2022;12:1011.
In the United States, there are approximately 1.4 million Salmonella infections each year, mostly non-typhoidal and mostly presenting as uncomplicated gastroenteritis. Bloody diarrhea is possible (more so in children than in similarly infected adults). Concomitant bacteremia occurs in 3.3% to 15.1%, usually in those with fever lasting five or more days. Most Salmonella gastroenteritis is self-limited, and antibiotics are not only ineffective but might increase shedding of Salmonella in the stool. Evidence-based guidelines suggest that blood cultures and antimicrobial administration be reserved for those with prolonged fever, severe diarrhea, and specific risk factors that raise the possibility of severe illness (age younger than 3 months, immunocompromising condition, and/or signs of disseminated infection or septicemia).
The advent of molecular panel testing means that Salmonella-positive results can come back within as little as two hours, a significant improvement over stool culture results that can take up to three days. The use of gastrointestinal pathogen panels has been associated with improved antimicrobial stewardship and reduced healthcare costs in adults. In children, however, there are improved patient outcomes and reduced expenditures for the small subset of patients who have gastrointestinal pathogens for which antimicrobial therapy is helpful; considering pathogen panel testing for all children with gastroenteritis, though, molecular testing did not improve either outcomes or costs.
Looking historically over the years before and after molecular pathogen panel testing became available, O’Boyle and colleagues in Virginia compared the management and outcomes of children with non-typhoidal Salmonella gastroenteritis prior to and then with molecular testing being possible. Children younger than 18 years of age in a large healthcare system in the southeastern United States were included in a study that ranged from 2008 to 2018. (Gastrointestinal molecular panel testing became available in this setting in 2016, with results typically available within two hours of the sample being obtained.) Patients with hemoglobinopathies and/or immunocompromising conditions were excluded from this study. Chart reviews were done.
A total of 965 patients were identified who had nontyphoidal Salmonella gastroenteritis and did not have a hemoglobinopathy and were not immunocompromised. Of these, 27% had molecular pathogen testing, and the other 73% had stool cultures done. The molecular and culture groups had similar numbers of children who were younger than 3 months of age (7% to 8%) and similar percentages of children with diarrhea, fever, and prolonged fever. Similar percentages of children looked ill in the two testing groups. C-reactive protein levels and white blood cell counts were similar between the two groups. Thus, there was not objective evidence that children were younger or sicker in either of the two testing groups.
Children with rapid Salmonella positivity (that is, those positive quickly with molecular testing as opposed to those positive a couple of days later with culture testing) were significantly more likely to be admitted to the hospital (69% vs. 49%), but, once admitted, had shorter lengths of stay (2.8 days vs. 3.8 days). Children with rapid Salmonella positivity were more likely to have blood cultures done (54% vs. 44%) but were less likely to have positive blood cultures (6% vs. 8%). Children with rapid Salmonella positivity also were more likely to receive antibiotic treatment than those who “just” had positive culture results (49% vs. 34%). There was no difference in the number of children requiring subsequent care (re-visits, re-admissions) attributable to the gastrointestinal infection based on the type of microbiology testing done.
Using odds ratios, the authors summarized, saying that molecular testing yielded a 2.3-fold risk of hospital admission, a 1.6-fold risk of having a blood culture done, and a two-fold risk of receiving antibiotics despite having nearly identical rates of concurrent bacteremia, looking ill, and being younger than 3 months of age. Thus, availability of rapid molecular testing prompted physicians to do tests more frequently and provide treatment counter to established evidence-based guidelines. Gently, the authors proposed that their results “suggest a need for increased diagnostic stewardship.”
COMMENTARY
In 1709, English poet Alexander Pope wrote that “a little learning is a dangerous thing.” He likened eager learning to thirsty drinking and suggested that small doses of learning intoxicate the brain while “drinking largely” allows for sober thinking. Probably incorrectly, more recent writers have credited Albert Einstein and others with saying “a little knowledge is a dangerous thing.”
It is common knowledge that some pediatric patients have a risk of serious disease with Salmonella infections — especially young infants and patients with sickle cell disease. It is also known that some Salmonella — especially Salmonella typhi — can cause serious illness. Somehow that “little learning” or “little knowledge” seems to prompt dangerous physician behavior – testing for bacteremia in patients unlikely to benefit from such testing and giving antimicrobial therapy to patients unlikely to benefit from such treatment (and even potentially to be harmed by it).
Using a modified Delphi technique to determine what experts thought was important in etiologic testing of gastroenteritis, a combined U.S.-Canada team reported that there was strong consensus that there were good clinical and public health reasons to advocate for etiologic testing of some children with acute gastroenteritis, especially for immunocompromised children.1 Their report in October 2022 poignantly suggested that, in support of the use of etiologic testing, “diagnostic stewardship strategies can be employed, such as educating clinicians.”1 The even-newer data from O’Boyle and colleagues highlight the need for clinician education in dealing with rapidly available results about children with uncomplicated Salmonella gastroenteritis.
Another common bit of “little knowledge” is that pet reptiles are associated with Salmonella infections. Just last month (December 2022), a review of a recent decade of animal-associated outbreaks of salmonellosis was published.2 Animal contact accounts for 11% of the 1.4 million U.S. cases of salmonellosis each year, with the majority (62%) of outbreaks being linked to small turtles (those of less than 4 inches in size).2 Approximately half of the patients affected by Salmonella outbreaks were preschool-age children.2 Interestingly, 30% of their parents and caregivers were already aware of the risk of Salmonella from pet reptiles.2 Even if not dangerous, a “little knowledge” is not always applied in ways to reduce risks.
REFERENCES
- Tarr GAM, Persson DJ, Tarr PI, Freedman SB. Enteric pathogen testing importance for children with acute gastroenteritis: A modified Delphi study. Microbiol Spectr 2022;10:e0186422.
- Waltenburg MA, Perez A, Salah Z, et al. Multistate reptile- and amphibian-associated salmonellosis outbreaks in humans, United States, 2009-2018. Zoonoses Public Health 2022;69:925-937.
