Tests

1st tests to order

cerebrospinal fluid (CSF) cell count and differential

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Result
Test

A lumbar puncture to obtain CSF is the most important investigation when a diagnosis of bacterial meningitis is suspected; however, if lumbar puncture is delayed (e.g., due to awaiting imaging) this should not delay initiation of antibiotics.[59]

In untreated bacterial meningitis, typical findings in the CSF include pleocytosis, with WBC count typically >1000 cells/microliter and predominance of polymorphonuclear leukocytes.

More than 90% of patients present with CSF WBC count >100/microliter.[43] However, CSF WBC count can be normal in the early phase of the disease and in neonates.[65]


Diagnostic lumbar puncture in adults: animated demonstration
Diagnostic lumbar puncture in adults: animated demonstration

How to perform a diagnostic lumbar puncture in adults. Includes a discussion of patient positioning, choice of needle, and measurement of opening and closing pressure.


Result

polymorphonuclear pleocytosis

cerebrospinal fluid (CSF) protein

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Result
Test

In bacterial meningitis, CSF protein is usually elevated (>1.5 g/L; normal <0.5 g/L).[94]

Result

elevated

cerebrospinal fluid (CSF) glucose

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Result
Test

In bacterial meningitis, CSF glucose concentration is <45 mg/dL (<2.5 mmol/L), or <40% of simultaneously measured serum glucose.[43]

Result

low

cerebrospinal fluid (CSF) Gram stain

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Result
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Gram staining typically reveals the organism in 80% of cases.[43][Figure caption and citation for the preceding image starts]: Photomicrograph of Gram-stained Streptococcus species bacteriaImage provided by the CDC Public Health Image Library [Citation ends].com.bmj.content.model.Caption@7c593c66

However, diagnostic yields may be lower in patients who have received antibiotics before cultures are obtained.

Result

positive

cerebrospinal fluid (CSF) culture

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Result
Test

Bacterial culture of CSF is positive in 80% of untreated cases.[43]

However, diagnostic yields may be lower in patients who have received antibiotics before cultures are obtained.

Result

positive

antigen detection in cerebrospinal fluid (CSF)

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Result
Test

Serogroup A, B, C, Y, and W-135 polysaccharide antigen can be detected by latex agglutination in 22% to 93% of patients with meningococcal meningitis.[4] Antigen may persist in CSF for several days, making this test useful in patients treated with antibiotics before diagnostic specimens have been obtained and for the rapid presumptive diagnosis of meningococcal infection. Serogroup B Neisseria meningitidis and serotype K1 Escherichia coli polysaccharides cross-react, so test results should be interpreted cautiously in neonates. Antigen detection testing on body fluids other than CSF, including serum or urine, is not recommended because of poor sensitivity and specificity.

Result

N meningitidis capsular polysaccharide antigen

blood culture

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Result
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Performed ideally before giving antibiotics. However, taking blood for culture should not delay administration of antibiotics. The results of blood cultures may be influenced by previous antimicrobial therapy. For example, in one retrospective review blood cultures were positive in approximately 50% of untreated patients with meningococcal disease, but only 5% of patients who received an antibiotic before admission.[79]

Result

positive

CBC and differential

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Result
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Patients with bacterial meningitis may have an elevated WBC with a polymorphonuclear predominance. Patients with rapidly progressive infections, however, may initially have normal WBC. Neutropenia is not uncommon in severe infections. Thrombocytopenia and mild anemia are common.

Result

leukocytosis, anemia, thrombocytopenia

CRP

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Result
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Serum CRP tends to be elevated in patients with bacterial meningitis.

In patients where the cerebrospinal fluid (CSF) Gram stain is negative and the differential diagnosis is between bacterial and viral meningitis, a normal serum CRP concentration excludes bacterial meningitis with approximately 99% certainty.[80][81]

Result

high

electrolytes, calcium (Ca), magnesium (Mg), glucose

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Result
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Patients with severe bacterial meningitis often have metabolic abnormalities, especially acidosis, hypokalemia, hypoglycemia, and hypocalcemia.

Result

acidosis, low Ca/Mg, or hyper/hypoglycemia

coagulation profile (prothrombin time, INR, activated PTT, fibrinogen, fibrin degradation products)

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Result
Test

Coagulopathy is common in severe meningitis infections. Disseminated intravascular coagulation (DIC) is caused by acquired deficiencies of protein C, protein S, and antithrombin III; increases in plasminogen activator inhibitor and thrombin-activatable fibrinolysis inhibitor; and reduced activation of protein C on endothelial cells.

Result

evidence of DIC (prolonged thrombin time, elevated fibrin degradation products or D-dimer, low fibrinogen or antithrombin levels)

CT head

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Result
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Cranial CT scan should be considered before lumbar puncture in the presence of focal neurologic deficit, new-onset seizures, papilledema, altered mental state, or immunocompromised state to exclude a brain abscess or generalized cerebral edema.​[59]

Cranial imaging may be used to identify underlying conditions and meningitis-associated complications.

Brain infarction, cerebral edema, and hydrocephalus are common findings especially in pneumococcal meningitis.[86]

Result

normal or raised intracranial pressure or intracranial lesion if other pathologies present

polymerase chain reaction (PCR)

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Result
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PCR amplification of bacterial DNA from blood and cerebrospinal fluid (CSF) is more sensitive and specific than traditional microbiologic techniques. It is useful in distinguishing bacterial from viral meningitis.

PCR may also be helpful in diagnosing bacterial meningitis in patients who have been pretreated with antibiotics.[73]

Real-time PCR assay can identify specific serogroup (Neisseria meningitidis) or serotype (Haemophilus influenzae) from clinical isolates (typically blood or CSF).[95]

​​Multiplex PCR (such as the QIAstat-Dx Meningitis/Encephalitis [ME] Panel or the BioFire FilmArray ME Panel) is used to rapidly screen for multiple causative pathogens in a single reaction.[76][77][78]

Result

positive

Tests to consider

MRI head

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Result
Test

Should be used if there are focal neurologic signs.

Cranial imaging may be used to identify underlying conditions and meningitis-associated complications.

Brain infarction, cerebral edema, and hydrocephalus are common findings especially in pneumococcal meningitis.[86]

Result

normal or intracranial lesion if other pathologies present

transcranial Doppler

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Result
Test

Can be considered if there are concerns for vasculopathy associated with bacterial meningitis.[87]

Result

intracranial arterial stenosis of the middle cerebral artery and ischemia most common findings in acute meningitis

serum procalcitonin

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Result
Test

Sensitivity and specificity greater than 90% when used to distinguish between bacterial and viral meningitis.[82][83][84]​ Do not perform procalcitonin testing without an established, evidence-based protocol. When used appropriately there are significant opportunities to decrease unnecessary antimicrobial use.[85]

Result

normal or elevated

Emerging tests

heparin-binding protein (HBP)

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Result
Test

May have a role as a possible rapid biomarker for bacterial infections. In systematic review and meta-analysis studies HBP showed a high diagnostic accuracy of bacterial infections, including urinary tract infection and meningitis. However, further studies are needed to determine its prognostic value and whether it could guide antibiotic therapy.[88]

Result

elevated in bacterial infections

rapid antigen cerebrospinal fluid (CSF) tests

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Result
Test

May be useful in triaging pneumococcal meningitis.

A large systemic review and meta-analysis looked at using rapid antigen tests in CSF to triage and diagnose pneumococcal meningitis. The studies found the rapid antigen tests to have a sensitivity and specificity of 99.5% (95% confidence interval [CI], 92.4% to 100%) and 98.2% (95% CI, 96.9% to 98.9%), respectively. Further studies are warranted to investigate the accuracy of ruling out pneumococcal meningitis based on the results of these tests.[89]

Result

positive

metagenomic next-generation sequencing (mNGS)

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Result
Test

Diagnostic technique that sequences all the DNA and RNA in a sample to identify microbes. A systematic review and meta-analysis showed that in cases of unexplained bacterial meningoencephalitis, the mNGS of cerebrospinal fluid samples offered an advantage over conventional methods, especially in complex cases when a rare pathogen is implicated or the patient is on antibiotics.[90]

Result

positive

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