The research team, led by Juan Felipe Morantes Rubiano of Hospital Pablo Tobón Uribe and Universidad Pontificia Bolivariana, reviewed the records of 478 adults with suspected acute meningoencephalitis who underwent FAME testing at two tertiary hospitals in Medellín between 2019 and 2023. The cohort had a median age of 51 years and was 55 percent male. Of these patients, 353 were immunocompetent and 125 were immunosuppressed, a distinction that matters because clinicians have historically been reluctant to apply any restrictive testing rules to patients whose weakened immune systems can blunt the usual inflammatory signals of infection. Overall, only 14.8 percent of the FAME panels returned a positive result, a figure that immediately illustrates the scale of low-yield testing in routine practice.

The study’s design deserves careful attention because it differs from a classic diagnostic accuracy trial. The authors explicitly framed their work as a diagnostic stewardship evaluation rather than an assessment of how well spinal fluid chemistry detects confirmed central nervous system infection. The reason is subtle but important: the FAME panel itself is an imperfect reference standard, capable of missing genuine infections and occasionally detecting latent viruses that are not causing disease. Rather than claiming that routine measurements can diagnose meningoencephalitis, the researchers asked a narrower and more honest question: which cytochemical parameters predict that a FAME panel will come back positive? The target condition was therefore panel positivity, not microbiologically confirmed infection.

The differences between positive and negative cases were striking. Patients with positive panels had a median cerebrospinal fluid leukocyte count of 189 cells per cubic millimeter, compared with just 3 cells per cubic millimeter in those with negative panels. Protein concentration, a marker of blood-brain barrier disruption and inflammation, was also markedly higher in positive cases, with a median of 167 milligrams per deciliter versus 47 milligrams per deciliter. Glucose, which bacteria and viruses consume as they multiply, was lower in positive cases, at a median of 31 milligrams per deciliter compared with 62. Among all the parameters evaluated, protein showed the greatest discriminative capacity, with an area under the receiver operating characteristic curve of 0.793, while opening pressure, the pressure measured when the needle first enters the spinal canal, showed the weakest, at 0.666.

From these data, the team constructed a practical screening rule. Of the 478 tests performed, 287, or 60 percent, were carried out on samples without pleocytosis, defined as fewer than 10 white cells per cubic millimeter of fluid. In this low-cell-count group, the FAME positivity rate was only 5.5 percent. When the researchers added a second condition, requiring protein below 50 milligrams per deciliter, they identified 192 samples, or 40.1 percent of the total, in which positivity fell to just 2.6 percent. In other words, applying a combined threshold of at least 10 leukocytes per cubic millimeter or at least 50 milligrams per deciliter of protein would have flagged the samples most likely to be positive and spared the rest.

The clinical stakes of such a rule depend on what would have been missed. Under a narrow definition of clinically relevant results, meaning a positive test that would actually change patient management, only 0.5 percent of the low-yield samples would have contained such a finding. Under a broader definition, counting any confirmed true positive regardless of its management impact, the figure rose to 1.0 percent. These numbers quantify the trade-off at the heart of diagnostic stewardship: a modest risk of overlooking rare positives in exchange for a substantial reduction in testing that rarely helps. The combined threshold would have increased overall diagnostic yield by 55.4 percent while cutting low-yield testing by 40.1 percent, gains that translate directly into lower costs and faster laboratory turnaround for the samples that matter.

Perhaps the most consequential finding concerns immunosuppressed patients, a group usually excluded from restrictive testing guidelines because clinicians fear that their blunted inflammatory responses will produce false reassurance. In this cohort, the negative predictive value of the combined threshold was 97.4 percent overall and 96.0 percent in immunosuppressed patients, with a confidence interval of 86.5 to 98.9 percent for the latter group. That suggests the rule may be applicable even to patients with compromised immunity, though the authors caution that one clinically significant case in this subgroup would have been missed under the broader definition. The finding is hypothesis-generating rather than definitive, and the researchers emphasize that prospective validation is required before such thresholds are adopted into clinical pathways.

The concept of diagnostic stewardship, as opposed to antimicrobial stewardship, is gaining traction in infectious diseases. The idea is to intervene at the moment a test is ordered rather than after a result returns, ensuring that expensive diagnostics are directed at patients in whom they are most likely to change outcomes. Molecular syndromic panels like FAME test for a fixed menu of pathogens, including herpes simplex viruses, enteroviruses, cryptococcus, and several others, and each run carries a significant cost. When the pre-test probability of a positive result is low, as it evidently is in the majority of samples in this study, the marginal value of the panel diminishes. Simple, cheap cytochemical measurements performed on the same spinal fluid sample can serve as an inexpensive triage layer.

The study also illustrates the methodological caution needed when evaluating syndromic diagnostics. Because FAME served as the reference standard, the analysis cannot distinguish between true infections that the panel missed and latent viral detections that the panel flagged without clinical consequence. Herpes simplex virus DNA, for example, can persist in cerebrospinal fluid after treatment, and latent infections can produce positive results that do not reflect active disease. The authors’ decision to define their target as panel positivity rather than confirmed infection keeps the conclusions within defensible bounds, and their framing of the results as hypothesis-generating reflects that restraint. Any future implementation would need to weigh the rare missed positives against the systemic benefits of reduced testing, ideally through prospective studies that follow patients longitudinally.

For hospitals confronting the economics of molecular diagnostics, the Colombian data offer a concrete starting point for local evaluation. The thresholds involved, 10 leukocytes per cubic millimeter and 50 milligrams per deciliter of protein, are not exotic measurements but values already reported in every cerebrospinal fluid analysis, making implementation straightforward wherever FAME testing is available. The authors, who also included Laura Restrepo Álvarez, Andrea Mazo Cañola, Juan Pablo Villa Franco, Santiago Atehortúa Muñoz, Jorge Hernando Donado Gómez, and Paulina González Obando, received no direct monetary funding and declare no competing interests. If prospective validation confirms their findings, the humble spinal fluid cell count and protein level, measurements that have been part of neurology for more than a century, may become the first filter in a smarter, more sustainable diagnostic pathway for one of medicine’s most urgent syndromes.

Subject of Research: Cerebrospinal fluid cytochemical parameters as predictors of FilmArray Meningitis/Encephalitis panel positivity for diagnostic stewardship

Article Title: Cerebrospinal fluid cytochemical parameters as predictors of FilmArray Meningitis/Encephalitis panel positivity: a diagnostic stewardship approach in immunocompetent and immunocompromised patients

Article References: Morantes Rubiano, J. F., Restrepo Álvarez, L., Mazo Cañola, A., Villa Franco, J. P., Atehortúa Muñoz, S., Donado Gómez, J. H., & González Obando, P. (2026). Cerebrospinal fluid cytochemical parameters as predictors of FilmArray Meningitis/Encephalitis panel positivity: a diagnostic stewardship approach in immunocompetent and immunocompromised patients. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14575-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14575-x

Keywords: meningitis, encephalitis, cerebrospinal fluid, FilmArray, diagnostic stewardship, molecular diagnosis, pleocytosis, CSF protein, immunocompromised patients, diagnostic accuracy, BMC Infectious Diseases, Colombia

The core financial argument is striking. According to the authors’ estimates, a representative 200-bed community hospital that implements all five interventions could generate approximately $2.5 million to $2.8 million in annual laboratory and clinical savings. Beyond those direct savings, hospitals that improve their baseline performance on quality metrics could reduce penalties under the Centers for Medicare and Medicaid Services Hospital-Acquired Condition program by an estimated $200,000 to $600,000. The interventions may also improve publicly reported healthcare-associated infection metrics and strengthen hospital reputation, benefits that carry real competitive weight in an era when patients and payers increasingly scrutinize quality data.

Diagnostic stewardship, at its heart, is about ensuring the right test is ordered for the right patient at the right time—and that results are interpreted appropriately once they return. It is a discipline aimed at eliminating the cascade of harm that follows unnecessary or poorly targeted testing: false-positive results that trigger unneeded antibiotics, incidental findings that lead to invasive follow-up procedures, prolonged hospital stays, and wasted laboratory resources. Unlike efforts to restrict care, diagnostic stewardship refines decision-making at the moment a test is considered, making it an attractive target for both clinicians and administrators seeking measurable improvement.

The guide examines five common opportunities for improvement that recur across hospital settings. The first is optimizing testing for Clostridioides difficile, the bacterium responsible for severe, sometimes life-threatening diarrheal infections in healthcare settings. Because molecular assays can detect the organism in patients who are merely colonized rather than truly infected, testing unformed stools indiscriminately inflates infection rates and drives unnecessary treatment and isolation. The second and third targets are optimizing urine culture use and de-implementing unnecessary procalcitonin testing. Urine cultures ordered in patients without symptoms frequently reveal asymptomatic bacteriuria, a common finding that is often inappropriately treated with antibiotics, fueling resistance and adverse drug events. Procalcitonin, a biomarker sometimes used to guide antibiotic decisions, is frequently ordered in situations where the result will not change management, consuming resources without benefiting patients.

The remaining two interventions address the explosive growth of multiplex diagnostics. Optimizing respiratory pathogen panel use tackles panels that test for dozens of viruses and bacteria simultaneously in patients whose care would change little based on the full results, encouraging clinicians instead to select narrower panels or targeted tests matched to the clinical question. Optimizing blood culture use rounds out the list, addressing the widespread practice of drawing blood cultures from patients with low pretest probability of bloodstream infection or from indwelling lines where contamination is likely. Each unnecessary culture carries costs in laboratory processing, false-positive contamination that prompts additional testing and antibiotics, and extended lengths of stay when ambiguous results are reflexively treated.

For each of the five interventions, the authors lay out implementation strategies, projected financial impact, and practical examples that hospitals can adapt to their own circumstances. The financial models are designed to translate clinical improvements into the language of hospital administration: avoided laboratory costs, reduced antibiotic expenditures, shortened lengths of stay, and improved quality measure performance. That translation matters, because diagnostic stewardship programs typically require upfront investment in education, electronic health record modifications, and personnel time, and program champions must often justify those costs to budget-conscious executives before any savings are realized.

Senior author Sarah E. Turbett, MD, framed the resource as a bridge between clinical value and operational performance. Healthcare leaders know that every investment must improve both patient care and operational performance, she noted, and this framework helps hospitals evaluate and implement diagnostic stewardship in ways that improve clinical outcomes, strengthen quality metrics, and demonstrate measurable value. The emphasis on measurable value reflects a growing recognition that programs perceived as purely clinical initiatives often struggle to survive budget cycles, while those with robust business cases secure sustained institutional support.

The publication arrives at a moment when diagnostic excellence is receiving increasing national attention. The Centers for Disease Control and Prevention’s Core Elements of Hospital Diagnostic Excellence identifies diagnostic stewardship as a key strategy for improving diagnosis while advancing healthcare quality, safety, and value-based care. By aligning its guidance with that national framework, SHEA positions diagnostic stewardship as a central pillar of hospital quality improvement rather than a niche laboratory concern, giving infection preventionists, laboratory directors, and antimicrobial stewardship teams a shared vocabulary for engaging executive leadership.

The guide was developed by SHEA’s Diagnostic Stewardship Special Interest Group, a body convened specifically to advance this field, and it is aimed at a broad professional audience: healthcare executives, laboratory leaders, infection prevention professionals, antimicrobial stewardship teams, and frontline clinicians. Each of these groups plays a distinct role in making diagnostic stewardship succeed. Executives control the resources, laboratory leaders understand the technical nuances of test performance and utilization, infection prevention teams track the downstream effects on healthcare-associated infection metrics, stewardship programs connect testing behavior to antibiotic use, and clinicians ultimately decide which tests to order and how to interpret them.

For hospitals weighing whether to act, the combined figures offer a compelling bottom line. Direct savings of $2.5 million to $2.8 million annually, plus up to $600,000 in avoided CMS penalties, represent the kind of return that few quality initiatives can match—achieved largely by doing fewer, better-targeted tests rather than buying new technology. The authors emphasize that actual results will vary with each hospital’s baseline performance, patient population, and existing stewardship infrastructure, which is precisely why the guide insists on institution-specific business cases rather than one-size-fits-all projections. What the resource makes clear is that diagnostic stewardship has matured from a conceptual ideal into an operational discipline with documented strategies, modeled financial impact, and demonstrated potential to improve patient care, healthcare quality, and hospital finances simultaneously. As pressure mounts to deliver safer, higher-value care, the guide suggests that one of the most powerful tools available to hospitals may be simply ordering the right test, for the right patient, at the right time.

Subject of Research: Building hospital business cases for diagnostic stewardship interventions to improve patient care and reduce costs

Article Title: SHEA publishes resource to help hospitals build the business case for diagnostic stewardship

Article References: SHEA publishes resource to help hospitals build the business case for diagnostic stewardship. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: diagnostic stewardship, SHEA, hospital savings, Clostridioides difficile testing, urine culture, procalcitonin, respiratory pathogen panels, blood culture, antimicrobial stewardship, CMS penalties, healthcare quality, infection prevention