Which patients with presumed acute infectious diarrhea in an outpatient setting should undergo gastrointestinal pathogen panel testing?

ACUTE DIARRHEA DEFINED

Diarrhea occurs when the normal physiologic processes of the small and large intestines are disrupted. These organs typically absorb ions, substrates, and water. Diarrhea results from either reduced water absorption or increased water secretion in the intestines, leading to excessive fluid in the stool.

The American College of Gastroenterology¹ describes acute diarrhea as passage of unformed, loose, or watery stool for a duration of less than 2 weeks. In contrast, chronic diarrhea lasts more than 4 weeks. Acute diarrhea is often caused by viruses, bacteria, or parasites.²

Chronic diarrhea is less likely to be infectious but may be related to parasitic infections.¹ Distinguishing between infectious and noninfectious causes of diarrhea is crucial for guiding the clinical approach and determining appropriate management strategies.

WHAT ARE COMMON INFECTIOUS CAUSES OF ACUTE DIARRHEA?

Common bacterial causes of acute diarrhea include Salmonella, Campylobacter, Escherichia coli, Shigella, and Clostridioides difficile. Bacterial infections are associated with travel, food ingestion, and antibiotic use.³ A specific cause can often be found based on the exposure history.

Common viral causes include norovirus and rotavirus. Norovirus causes acute diarrhea outbreaks worldwide, often in close-containment settings such as dormitories, nursing facilities, cruise ships, and hospitals. Rotavirus is commonly found in children younger than 5 years. However, cases have decreased in high-income countries due to increased rotavirus vaccination rates.²

Parasitic and protozoal causes of acute diarrhea are typically acquired through ingesting contaminated water or food or person-to-person transmission. Parasites and protozoans are a significant cause of morbidity and mortality, specifically in low-income countries. Common organisms in the United States include Giardia duodenalis (also known as G lamblia or G intestinalis), Cryptosporidium species, Cyclospora, and Entamoeba histolytica.²

CONSIDERATIONS WHEN ORDERING A GASTROINTESTINAL PATHOGEN PANEL

Six multiplex PCR gastrointestinal pathogen panels are approved by the US Food and Drug Administration (Table 1).⁶ These panels test for up to 22 enteropathogens (bacteria, viruses, parasites) and, compared with traditional culture methods, have increased sensitivity of organism detection as well as a faster turnaround time.⁷ The ability to detect a broad range of pathogens helps clinicians tailor treatment more effectively, particularly in patients with complex clinical presentations.^1,7

Considerations when ordering a multiplex panel include clinical history and presentation, the type and number of organisms to be tested for, treatment implications based on diagnostic results, test cost for the patient, and the patient population tested. Although recommendations from the Centers for Medicare & Medicaid Services generally guide insurance providers, some insurance plans may limit coverage to panels with fewer than 5 targets.⁸ The lack of consistency across insurance plans accentuates the need for clinicians to be aware of limitations in coverage when recommending diagnostic tests.

Also, multiplex pathogen panels detect the toxin genes in C difficile, a result that needs to be correlated clinically and confirmed by an additional test such as the antigen test for C difficile toxin.² When bacterial pathogens are detected, bacterial culture may be needed for susceptibility testing and to fulfill public health reporting requirements and provide epidemiologic data.⁶

Gastrointestinal pathogen panels play an essential role in public health surveillance. They also can improve clinical management and reduce healthcare costs.⁶ A retrospective observational study assessed diagnostic methods for acute infectious gastroenteritis using data from 36,787 outpatients with this diagnosis who had a traditional workup (eg, bacterial culture, antigen testing, microscopy), multiplex PCR panel testing with less than 12 target pathogens, or multiplex PCR panel testing with 12 or more target pathogens.⁹ This study supported the cost-effectiveness and clinical utility of large multiplex PCR panels (> 12 targets) in diagnosing acute infectious gastroenteritis, finding that such panels were associated with greater diagnostic yield, lower 30-day follow-up cost, and reduced hospitalization risk compared with a traditional workup.

In the case example, multiplex testing for 22 enteropathogens was positive for Salmonella species. The patient was immunocompromised and was successfully treated with antibiotics. The possible source of his diarrheal illness was cucumbers that had been recalled due to Salmonella contamination.¹⁰

THE BOTTOM LINE

Timely diagnosis and treatment of diarrhea are essential in specific patient populations, including those who are immunocompromised and are at increased risk of complications. Testing using multiplex gastrointestinal pathogen panels, available in most microbiology laboratories, provides accurate detection of a broad range of pathogens in a timely, cost-effective manner and can improve patient outcomes.

DISCLOSURES

Dr. Hata has disclosed serving as a research principal investigator for Roche Molecular and teaching and speaking for Seegene. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.