Diagnostic Stewardship & Molecular Assays: A Laboratorian’s Primer

Diagnostic stewardship (DxS) has become increasingly important as healthcare shifts toward value-based care models focused on improving outcomes while controlling costs. DxS refers to processes that optimize laboratory testing to ensure the right test is used for the right patient at the right time, ultimately prompting the right clinical action. While stewardship can occur throughout the testing lifecycle, the greatest opportunity for impact lies in the pre-analytical phase, including test ordering, patient selection, and specimen collection. Because these processes often occur outside the laboratory, successful DxS programs require collaboration among laboratorians, clinicians, pharmacists, infection prevention teams, information technology specialists, and hospital leadership.

Molecular diagnostic assays are especially well suited for stewardship because they offer rapid, highly sensitive pathogen detection but are also associated with significant complexity, cost, and risk for misinterpretation. Positive molecular results may represent colonization, prolonged nucleic acid shedding, or clinically insignificant findings rather than active infection. Without appropriate utilization strategies, these assays can contribute to unnecessary treatment, excessive costs, and diagnostic confusion.

An essential first step in a DxS initiative is identifying high-impact tests for evaluation through review of institutional data such as utilization patterns, appropriateness, positivity rates, turnaround times, and downstream clinical impact. Successful programs rely on multidisciplinary collaboration that includes laboratory administration, physicians, pharmacists, infection prevention specialists, antimicrobial stewardship teams, IT personnel, and executive leadership.

Most effective interventions focus on improving pre-analytical decision-making. Clinician education remains foundational, but electronic health record tools such as clinical decision support systems, best practice alerts, nudges, and optimized order sets are increasingly valuable in guiding appropriate testing. More restrictive approaches, including cascading or conditional testing, may also be used for complex or costly molecular assays. In some cases, orders may require approval by infectious disease specialists, pathologists, or stewardship committees. While restrictive strategies can reduce inappropriate utilization, they must be carefully implemented to avoid limiting access to necessary testing.

Continuous monitoring and feedback are critical to maintaining successful DxS programs. Key metrics typically focus on utilization, diagnostic performance, and clinical impact, including testing volume, repeat testing, adherence to criteria, positivity rates, antimicrobial utilization, time to treatment changes, and cost avoidance. Importantly, stewardship success is not solely defined by reduced testing volume. Stable or increased utilization may still represent success if testing becomes more clinically appropriate or reflects changes in disease epidemiology.

The article highlights multiplex polymerase chain reaction (mPCR) gastrointestinal panels as an example of molecular DxS in practice. These panels rapidly detect a broad range of pathogens and often outperform traditional stool cultures in diagnostic yield and turnaround time. However, their high sensitivity can create interpretation challenges because positive results may not distinguish active infection from asymptomatic carriage or residual shedding. Effective stewardship strategies include limiting testing to patients with appropriate clinical features such as fever, bloody diarrhea, or prolonged symptoms. Testing is often discouraged in patients hospitalized for more than three days due to low diagnostic yield and increased likelihood of detecting colonizing organisms such as Clostridioides difficile.

Similarly, stewardship strategies for cerebrospinal fluid (CSF) mPCR panels used in suspected meningitis or encephalitis often restrict testing to patients with objective evidence of central nervous system inflammation, such as CSF pleocytosis. Studies show this approach can reduce unnecessary testing while improving positivity rates. However, stewardship protocols must remain flexible because some viral infections and immunocompromised patients may present without elevated CSF white blood cell counts.

Affiliations

1. Department of Pathology, New York University, New York, NY, USA.
2. Department of Pathology, Rush University Medical Cetner, Chicago, IL, USA
3. bioMérieux, Medical Affairs, Salt Lake City, UT, USA