≈ Evidence Verdict — Mixed: Evidence is conflicted regarding the diagnostic sensitivity of procalcitonin depending on the sample type (Henry 2016 shows 96% sensitivity in serum, while Sanaei Dashti 2017 shows only 68.6% in CSF) and the reliability of clinical prediction rules in neonates (Burstein 2026 vs. Pishori 2023). Clinicians should prioritize serum procalcitonin over CSF procalcitonin for etiological differentiation and maintain a low threshold for lumbar puncture in neonates, as clinical signs and prediction rules may not reliably exclude meningitis in this population.

Framework: PIRD

⚖︎ Contradictory Evidence

While biomarkers and rapid tests show high accuracy, evidence is conflicted regarding the sensitivity of procalcitonin across different sample types and the reliability of clinical prediction rules in neonates.

Diagnostic sensitivity of Procalcitonin (PCT) for bacterial meningitis
Supporting: Serum PCT is highly accurate for differentiating bacterial from viral meningitis in children, with a pooled sensitivity of 0.96. [3]
Opposing: CSF procalcitonin demonstrates poor diagnostic sensitivity (68.6%) for bacterial meningitis, despite high specificity. [13]
Reliability of clinical triage for meningitis in febrile infants
Supporting: The PECARN prediction rule accurately identifies febrile infants aged 28 days or younger at low risk for invasive bacterial infections, including meningitis. [14]
Opposing: Clinical features in neonates are non-specific and overlap significantly with sepsis, making it challenging to reliably identify meningitis based on clinical signs alone. [12]
Reliability of CSF culture as the diagnostic reference standard
Supporting: Conventional microbiological assays and CSF cultures are treated as the definitive reference standard for evaluating new rapid antigen tests. [2]
Opposing: CSF culture is an imperfect reference standard, particularly in partially treated cases, and inconsistent reference standards contribute to a high risk of bias in diagnostic studies. [1, 20]

This page covers Diagnostic Test of Choice for Meningitis, a topic in Internal Medicine.

Deep Dive — Evidence Details

References

[1]
Groeneveld NS, Bijlsma MW, van de Beek D et al.. “Biomarkers in paediatric bacterial meningitis: a systematic review and meta-analysis of diagnostic test accuracy.” Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2025). PMID: 39672463 ↗
L1SR_OBSCited in: Clinical Bottom Line, Comparative Accuracy and Alternatives, Limitations and Certainty
[2]
Someko H, Okazaki Y, Tsujimoto Y et al.. “Diagnostic accuracy of rapid antigen tests in cerebrospinal fluid for pneumococcal meningitis: a systematic review and meta-analysis.” Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2023). PMID: 36503113 ↗
L1SR_OBSCited in: Clinical Bottom Line, Index Test Performance vs. Reference Standard, Comparative Accuracy and Alternatives
[3]
Henry BM, Roy J, Ramakrishnan PK et al.. “Procalcitonin as a Serum Biomarker for Differentiation of Bacterial Meningitis From Viral Meningitis in Children: Evidence From a Meta-Analysis.” Clinical pediatrics (2016). PMID: 26378091 ↗
L1SR_OBSCited in: Clinical Bottom Line
[4]
Ernawati E, Akbar MIA, Aryananda RA et al.. “HELLP syndrome as a major contributor to adverse maternal and neonatal outcomes among preeclamptic women: findings from a multicenter retrospective cohort study.” BMC pregnancy and childbirth (2025). PMID: 41430585 ↗
L3COHORTCited in: Clinical Scenario and Population
[5]
Mandelbrot L, Kennedy S, Rousseau J et al.. “Predicting neonatal infection in preterm premature rupture of membranes with vaginal microbiology and metagenomics: a prospective cohort study.” American journal of obstetrics and gynecology (2026). PMID: 41421745 ↗
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[6]
Ssentongo SM, Ojok B, Opito R et al.. “Prevalence and risk factors of neonatal sepsis in the neonatal intensive care unit at Soroti Regional Referral hospital, Uganda: a retrospective study.” BMC pregnancy and childbirth (2025). PMID: 41254579 ↗
L3COHORTCited in: Clinical Scenario and Population
[7]
Wang H, Xu X, Zhang M et al.. “The delivery modes and morbidity/mortality in very preterm infants with birth weight <1,500 g: a retrospective cohort study.” Frontiers in public health (2025). PMID: 41211398 ↗
L3COHORTCited in: Clinical Scenario and Population
[8]
Taweephol T, Pongpitakmetha T, Boonwan N et al.. “Clinical characteristics and factors associated with tuberculous meningitis outcomes in Thailand: A 13-year retrospective cohort study.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2025). PMID: 41173203 ↗
L3COHORTCited in: Clinical Scenario and Population
[9]
Yadav B, Gupta N, Sasidharan R et al.. “Extensively drug-resistant gram-negative sepsis in a neonatal intensive care unit from western India: A retrospective cohort study.” The Indian journal of medical research (2026). PMID: 42024915 ↗
L3COHORTCited in: Clinical Scenario and Population
[10]
Özdemir F, Birtane D, Yılmaz N et al.. “Intensive Care Management and Outcomes of Neuroleptic Malignant Syndrome: A Single-Center Retrospective Study.” Medicina (Kaunas, Lithuania) (2026). PMID: 41752777 ↗
L4COHORTCited in: Clinical Scenario and Population
[11]
Fabbri IS, Pagano T, Darin Y et al.. “Safety and Efficacy of Noninvasive Ventilation in Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease and Decreased Level of Consciousness: A Retrospective Study.” The clinical respiratory journal (2026). PMID: 41603294 ↗
L3COHORTCited in: Clinical Scenario and Population
[12]
Pishori T, Furia FF, Manji K. “A cross-sectional study of clinical features of bacterial meningitis among neonates presumed to have sepsis in a tertiary hospital, Dar es Salaam, Tanzania.” The Pan African medical journal (2023). PMID: 38465011 ↗
L3OTHERCited in: Index Test Performance vs. Reference Standard
[13]
Sanaei Dashti A, Alizadeh S, Karimi A et al.. “Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis: A cross-sectional study.” Medicine (2017). PMID: 28858084 ↗
L2OTHERCited in: Index Test Performance vs. Reference Standard
[14]
Burstein B, Waterfield T, Umana E et al.. “Prediction of Bacteremia and Bacterial Meningitis Among Febrile Infants Aged 28 Days or Younger.” JAMA (2026). PMID: 41359314 ↗
L1SR_OBSCited in: Comparative Accuracy and Alternatives
[15]
Staal SL, Olie SE, Ter Horst L et al.. “Granulocytes in cerebrospinal fluid of adults suspected of a central nervous system infection: a prospective study of diagnostic accuracy.” Infection (2024). PMID: 38520645 ↗
L1COHORTCited in: Comparative Accuracy and Alternatives
[16]
Chekrouni N, van Soest TM, da Cruz Campos AC et al.. “Bacterial load in cerebrospinal fluid predicts unfavourable outcome in pneumococcal meningitis: a prospective nationwide cohort study.” Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2024). PMID: 38479702 ↗
L2COHORTCited in: Comparative Accuracy and Alternatives
[17]
Groeneveld NS, Olie SE, Visser DH et al.. “Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2024). PMID: 38395221 ↗
L2COHORTCited in: Comparative Accuracy and Alternatives
[18]
Jiang YK, Zhou LH, Cheng JH et al.. “Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.” Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2024). PMID: 38295989 ↗
L3COHORTCited in: Comparative Accuracy and Alternatives
[19]
Kadambari S, Feng S, Liu X et al.. “Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study.” The Pediatric infectious disease journal (2024). PMID: 38190645 ↗
L3COHORTCited in: Comparative Accuracy and Alternatives
[20]
Temfack E, Rim JJB, Spijker R et al.. “Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2021). PMID: 32829406 ↗
L1SR_OBSCited in: Limitations and Certainty
[21]
Ellis J, Luintel A, Chandna A et al.. “Community-acquired acute bacterial meningitis in adults: a clinical update.” British medical bulletin (2019). PMID: 31556944 ↗
L5SR_OBSCited in: Limitations and Certainty
[22]
Zimmermann P, Curtis N. “Bacterial Meningitis in the Absence of Pleocytosis in Children: A Systematic Review.” The Pediatric infectious disease journal (2021). PMID: 33591075 ↗
L4SR_OBSCited in: Limitations and Certainty
[23]
van Zeggeren IE, Bijlsma MW, Tanck MW et al.. “Systematic review and validation of diagnostic prediction models in patients suspected of meningitis.” The Journal of infection (2020). PMID: 31794775 ↗
L1SR_OBSCited in: Limitations and Certainty
[24]
Poletto E, Zanetto L, Velasco R et al.. “Bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infection: a systematic review.” European journal of pediatrics (2019). PMID: 31473824 ↗
L2SR_OBSCited in: Limitations and Certainty