Faster Results, Better Care? Impact of Meningitis/Encephalitis Syndromic Panel Testing on Pathogen Detection and Hospital Outcomes Beyond CSF Culture: A Literature Search for Diagnosticians
Abstract
1. Introduction
2. Methods
3. Results
3.1. The Diagnostic Performance of Meningitis Panels
3.2. The Pathogen-Specific Performance and False Results
3.3. The Value of Ancillary Testing
3.4. The Impact on Clinical Outcomes and Timing
3.5. The Effect of Antimicrobial Use
3.6. The Effect on the Length of Stay at the Hospital
3.7. The Pathogen Type and Clinical Impact
3.7.1. Age-Related Variations in M/E Panel Results
3.7.2. Economic Impact of the M/E Panel
4. Discussion
4.1. Limitations and Challenges
4.1.1. Regional and Clinical Challenges
4.1.2. The Role of Antimicrobial Stewardship
4.2. Future Directions
4.2.1. Diagnostic Stewardship and Optimization Strategies
4.2.2. The Implementation in Low-Resource Settings
4.2.3. Algorithm-Guided Testing—The Integration of Biochemical Markers
4.3. Artificial Intelligence (AI) and Machine Learning (ML) in Meningitis Diagnostics
4.3.1. Application of AI in Pathogen Detection—Metagenomics
4.3.2. Prognosis and Outcome Prediction
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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| Authors | Location | Sensitivity | Specificity | False Positives and Negatives |
|---|---|---|---|---|
| [9] | Eleven geographically distinct U.S. sites over a period of approximately eight months (February–September 2014). | 100% for 9 over 14 pathogens; 95.7% for enteroviruses, 85.7% for HHV-6, 0% sensitivity for Streptococcus agalactiae. | More than 99.2% for most pathogens. | One false positive and false negative result for Streptococcus agalactiae, for a sensitivity. |
| [6] | Review article that included many centers, 56 centers in eight countries: Canada, Chile, India, Lithuania, Mexico, Peru, Russia, and the United States. Fifty-eight centers in seven countries: the United States, Canada, Argentina, Russia, India, Estonia, and Lithuania. A total of 77 centers in nine countries: Argentina, Brazil, Canada, Chile, Germany, Republic of South Africa, Spain, the United Kingdom, and the United States. A total of 28 centers in four countries. | Approximately 90%. | Approximately 97%. | False positives in low prevalence areas and false negatives for low viral or bacterial load. |
| [11] | Los Angeles County + University of Southern California Medical Center and Harbor-UCLA Medical Center are two tertiary cares | 100% for bacteria, 50% for fungi such as Cryptococcus neoformans. | 99.9% for bacteria, 100% for fungi. | Some positive cryptococal antigens and cultures had variable panel results. |
| [7] | Systematic review/study location not mentioned | More than 95%. | More than 99%. | Some false positives are present, false negatives for low viral or bacterial load. |
| [4] | Systematic review/study location not mentioned | Approximately 90%. | Approximately 97%. | Some false positives are present, false negatives for low viral or bacterial load. |
| [2] | Salt Lake City, USA | 96.4% | 95.24% | Some false positives and false negatives have been resolved via comparator PCR or sequencing. |
| Pathogen | Type of Error | High-Risk Pitfalls | Clinical Implications |
|---|---|---|---|
| HHV-6 [9] | False positive | Detection is usually an indication of infection in ciHHV-6 or of silent congenital infection, but not of acute disease. | Inappropriate antiviral use and diagnosis in neonates. |
| HSV-1/2 [9] | False positive | Four false-positive results in total. | Inappropriate antiviral use such as acyclovir. |
| Streptococcus pneumoniae [9,15] | False positive | Twelve false positives are high, mostly because of contamination. | Inappropriate antibacterial use, longer LOS. |
| Streptococcus agalactiae (GBS) [15] | False positive and negative | False positives (15.4% in one analysis) and false negatives, which are persistent and occasional, respectively. | Wrong or delayed treatment in neonates. |
| Cryptococcus neoformans [11] | False negative | Decreased sensitivity in low fungal burden or in treated patients. CrAg may stay positive despite negative panel results | Delayed diagnosis in immunocompromised patients. |
| Listeria monocytogenes [14] | False negative | Characteristic clinical presentation with limited panel sensitivity. A negative panel should not exclude high suspicion. | Delayed proper antimicrobial use. |
| CSF Culture | Multiplex PCR M/E Panel | |
|---|---|---|
| Method [17,18] | Organisms are grown on media with MALDI, along with biochemical means. | Nucleic acid amplification with PCR detects a set of viral, fungal, and bacterial pathogens that are previously defined. |
| Turnaround time [18,19] | Approximately 24 to 72 h for bacteria, however it is longer for fungi and mycobacteria. Gram stain may allude to a preliminary result, which is faster. | Approximately 1 to 2 h in total (with the use of single-run cartridges). |
| Organisms detected [24] | May depend on culture techniques but can be any cultivable organism. | Limited to the pathogens that are previously defined, such as common ones. Cryptococcus neoformans may be present on some panels, however, unlisted, rare, or novel organisms are often absent. |
| Sensitivity for bacterial pathogens [15] | It is the gold standard; however, sensitivity depends on the use of prior antibiotics and bacterial load. | Sensitivity does not depend on the use of previous antibiotics. It is generally higher than cultures but may change depending on organisms. |
| Sensitivity for viral pathogens [4,18] | Culture is usually poor for viruses, and the latter is either slow or did not occurred usually. | Sensitivity is high compared to conventional methods including LDT PCR that are virus dependent. The panels can usually detect enteroviruses, HSV, VZV. |
| False positives [4,21] | Contamination may lead to false positives, but it is usually low for pathogens that are clinically significant. | If there are false positives, they generally require correlation with clinical data, which may impact treatment management and length of stay. |
| Pathogen load [9,22] | Cultures cannot provide Ct values, which correspond to the number of amplification cycles, which are required for the sample’s signal to cross the specific threshold that is set. | Some panels can include Cts, however reading is often qualitative (either a positive or a negative result) |
| Effect due to previous antibiotic use [15] | Antibiotics strongly affect culture results. | PCR usually detects nonviable RNA or DNA; thus it is more possible for it to stay positive, even after antibiotic use. |
| Effect on management [21] | It is essential for susceptibilities leading to target therapies. | Time for antibiotic use may be reduced, leading to shorter hospital stays and de-escalations in case of negative pathogens. However, stewardship varies, and impact may vary. |
| Cost [4] | Cost is usually lower; however, it requires developed and clean laboratory infrastructures. Per sample, the culture ends up being less expensive. | Each test costs higher (priced per cartridge or platform), depending on the equipment’s quality. |
| Implications and Regulations [4,23] | CSF cultures are widely available and are part of the standard care. | Some panels are FDA panels and used globally, however proper implementation needs stewardship with validation and algorithms for proper reporting and interpretation. |
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Toutounji, K.; Jreissati, J.-M.T.; Mahfouz, R. Faster Results, Better Care? Impact of Meningitis/Encephalitis Syndromic Panel Testing on Pathogen Detection and Hospital Outcomes Beyond CSF Culture: A Literature Search for Diagnosticians. Diagnostics 2026, 16, 691. https://doi.org/10.3390/diagnostics16050691
Toutounji K, Jreissati J-MT, Mahfouz R. Faster Results, Better Care? Impact of Meningitis/Encephalitis Syndromic Panel Testing on Pathogen Detection and Hospital Outcomes Beyond CSF Culture: A Literature Search for Diagnosticians. Diagnostics. 2026; 16(5):691. https://doi.org/10.3390/diagnostics16050691
Chicago/Turabian StyleToutounji, Kayanne, Jean-Marc T. Jreissati, and Rami Mahfouz. 2026. "Faster Results, Better Care? Impact of Meningitis/Encephalitis Syndromic Panel Testing on Pathogen Detection and Hospital Outcomes Beyond CSF Culture: A Literature Search for Diagnosticians" Diagnostics 16, no. 5: 691. https://doi.org/10.3390/diagnostics16050691
APA StyleToutounji, K., Jreissati, J.-M. T., & Mahfouz, R. (2026). Faster Results, Better Care? Impact of Meningitis/Encephalitis Syndromic Panel Testing on Pathogen Detection and Hospital Outcomes Beyond CSF Culture: A Literature Search for Diagnosticians. Diagnostics, 16(5), 691. https://doi.org/10.3390/diagnostics16050691

