- Clinical science
Meningitis is a serious infection of the meninges in the brain or spinal cord that is most commonly viral or bacterial in origin, although fungal, parasitic, and noninfectious causes are also possible. Enteroviruses and herpes simplex virus are the leading causes of viral meningitis, while Neisseria meningitidis and Streptococcus pneumoniae are the pathogens most commonly responsible for bacterial meningitis. Rarer forms of bacterial meningitis include tuberculous meningitis and Lyme-associated meningitis. The classic triad of meningitis is fever, headache, and neck stiffness. In infants and young children, the presentation is often nonspecific. Patients may also present with neurological deficits, altered mental status, and seizures, indicating increased intracranial pressure (ICP). The diagnosis is confirmed with lumbar puncture (LP) and CSF analysis. If increased ICP is suspected, a CT of the head should be performed first. Bacterial meningitis requires rapid initiation of empiric treatment. A life-threatening complication of bacterial meningitis (especially meningococcal meningitis) is Waterhouse-Friderichsen syndrome, which is characterized by disseminated intravascular coagulation and acute adrenal gland insufficiency. Viral meningitis typically resolves on its own and has a far less severe course than bacterial meningitis, which is generally fatal if left untreated. When N. meningitidis or S. pneumoniae are identified as the pathogen, the CDC should be notified and preventative measures taken to prevent dissemination of the infection.
- In the pediatric population, meningitis most often occurs in children < 1 year of age. 
- The median age of adult patients with meningitis is 43 years. 
- Worldwide, the incidence of meningitis caused by N. meningitidis is highest in sub-Saharan Africa, collectively referred to as the “meningitis belt.” 
Epidemiological data refers to the US, unless otherwise specified.
- CSF leak after head trauma or neurosurgery
- Maternal group B streptococcal infection during birth
- Immunocompromise (e.g., due to AIDS, asplenia, heavy alcohol use disorder, chronic illness, cancer, sickle cell anemia, old age, pregnancy)
- Crowded occupational or living conditions (e.g., college dormitories, military barracks, retirement homes, kindergartens)
- Close contact with an infected person
Common bacterial pathogens by patient group 
|< 1 month || |
|1 month – 2 years |
|2–50 years || |
|> 50 years |
|By underlying state|
|Basilar skull fracture |
|Penetrating trauma |
Less common bacterial pathogens
Viral meningitis: often associated with encephalitis (meningoencephalitis)
- Enteroviruses (especially coxackievirus and echovirus): the most common cause of meningitis in all patient groups 
- Herpesviruses: HSV (meningitis is more commonly caused by HSV2 than HSV1), CMV, EBV, VZV
- Lymphocytic choriomeningitis virus (LCMV)
- Mumps virus
- Some arboviruses; (e.g., West Nile virus, TBEV in Eurasia)
- Influenza virus
- JC virus 
- Candida spp.
- Aspergillus spp.
- Parasitic meningitis
- Noninfectious meningitis
Causes of meningitis in immunocompromised individuals
- Deficiency in various immune functions can predispose to certain types of meningitis. 
- Immunocompromised individuals are at increased risk of recurrent bacterial meningitis compared to those with intact immunity. 
- Viral: Risk is higher in individuals with cell-mediated immune deficiencies (e.g., in HIV infection). 
Fungal: Risk is higher in individuals with cell-mediated immune deficiencies (e.g. in HIV-infection). 
- Cryptococcus spp.
- Candida spp.
- Histoplasma capsulatum
- Aspergillus spp.
- Protozoal: Toxoplasma gondii (rare) 
Pathways of infection
Most pathogens that cause meningitis colonize the nasopharynx or the upper airways before entering the CNS via:
- Hematogenous dissemination . 
- Contiguous spread of infections in nose, eyes, and ears
- Retrograde transport along or within peripheral or cranial nerves
- Direct infection (e.g., due to trauma or head surgery) 
- Bacterial meningitis: usually 3–7 days 
- Viral meningitis: usually 2–14 day, depending on the type of virus
Clinical features of bacterial and viral meningitis are similar, although viral meningitis is less acute and usually self-limiting within 7–10 days.
In neonates, meningitis often manifests with nonspecific symptoms and without the classic triad of meningitis.
- Early symptoms
- Late symptoms
Children and adults
- Classic triad of meningitis: fever, headache, and neck stiffness (this triad is often not present in neonates and infants) 
- Altered mental status
- Nausea, vomiting
- Possibly cranial nerve palsies
- In the case of N. meningitidis
- Common symptoms of viral meningitis
Subarachnoid hemorrhage can manifest with the classic triad of meningitis but has a more sudden onset and patients often lose consciousness.
Physical examination 
Signs of meningeal irritation
- Systemic signs of inflammation
- Signs of increased intracranial pressure: : e.g., (< 5% of cases) 
Signs of underlying infections
- Bulging and redness of tympanic membrane: acute otitis media
- Skin manifestations 
Features suggestive of meningoencephalitis 
- Focal neurological signs (e.g., paresis, extrapyramidal symptoms, aphasia)
- Seizures (focal-onset or generalized)
- Behavioral changes, psychosis
- Altered consciousness
- Bacterial meningitis is a medical emergency and requires immediate treatment.
- Diagnostic and treatment steps should be initiated simultaneously and empiric treatment should not be delayed for diagnostic steps.
- If the patient is stable and has no contraindications: Perform LP as soon as possible before starting empiric antibiotics.
- If the patient is unstable, requires neuroimaging; (see criteria for imaging prior to LP in suspected meningitis), or has relative contraindications; to LP (e.g., coagulopathy): Defer LP and start empiric antibiotic treatment (see empiric antibiotic therapy for bacterial meningitis). 
Do not delay empiric antibiotic therapy in patients suspected of having bacterial meningitis.
- Bacterial meningitis can be rapidly progressive and life-threatening.
- Patients may present as critically ill and with complications (e.g., sepsis, multiorgan failure) requiring early aggressive supportive care.
- Empiric antibiotic treatment must be initiated as soon as possible (i.e., often prior to diagnosis).
- Obtain samples immediately for blood cultures, routine laboratory tests, and screening for organ dysfunction.
- Confirm the diagnosis with LP and CSF analysis (if no contraindications are present).
Start empiric antibiotics immediately after obtaining blood cultures and CSF samples. If LP is delayed for any reason (e.g., the need for a CT or hemodynamic stabilization), obtain blood cultures and administer antibiotics until it can be performed.
Laboratory studies 
- Blood cultures (two sets): obtain before starting antibiotic therapy
- BMP: Blood glucose is needed to analyze CSF glucose.
- CRP: elevated 
- Additional tests
Imaging is not necessary to establish the diagnosis of meningitis in most patients and should only be considered in patients with significant risk factors for complications.
- Recommended criteria for imaging prior to LP in suspected meningitis 
- Supportive findings
To remember the indications for imaging before LP, think of LP FAILS: Focal neurological deficits, Altered mental status, Immunocompromised or ↑ ICP, Lesions (space-occupying lesions in the brain), Seizures.
Approach to interpretation
Routine testing 
|Cerebrospinal fluid analysis in meningitis |
|Normal||Bacterial meningitis||Viral meningitis|
|Appearance|| || || |
|Cell count and differential|| || |
|Opening pressure || || || |
|Lactate || || || |
|Protein|| || || |
|Glucose|| || || |
|Gram stain and culture || || |
Atypical pathogen testing
Atypical pathogen testing is not necessary for all patients and should be performed as directed by clinical suspicion.
|Cerebrospinal fluid analysis in meningitis due to atypical pathogens |
|Tuberculous meningitis ||Lyme meningitis ||Cryptococcal meningitis |
|Appearance|| || || |
|Cell count and differential|
|Opening pressure|| || || |
|Lactate || || || |
|Protein|| || || |
|Glucose|| || || |
Additional microbiological testing
- Special microbiological stains
Special cultures 
- Viral culture
- M. tuberculosis cultures: Results can take up to 6 weeks. 
- Fungal cultures: for the identification of Candida spp., Cryptococcus spp. 
- For patients with CSF shunts or drains: Extend CSF cultures for at least 10 days.
- PCR for viral meningitis and specific bacterial subtypes 
Latex agglutination test 
- Bacterial antigen detection
- Fungal latex agglutinations: especially relevant for cryptococcal antigen testing (see cryptococcal meningitis)
- Apply appropriate isolation precautions.
- Stabilize the patient as needed.
Administer empiric antibiotics as soon as possible, preferably within 1 hour (see empiric antibiotic therapy for bacterial meningitis).
- If LP can be performed rapidly, administer antibiotics and adjuvant therapy (e.g., dexamethasone) after obtaining CSF.
- If LP is delayed (e.g., because neuroimaging is required), administer antibiotics and adjuvant therapy (e.g., dexamethasone) immediately.
- Add other antimicrobial therapy (e.g., antivirals, antifungals) as needed (see “Subtypes and variants” for details).
- Consult the infectious disease team.
- Tailor antimicrobial therapy once the pathogen is identified.
- Provide postexposure prophylaxis for close contacts if indicated (see postexposure chemoprophylaxis for bacterial meningitis).
- Airway management: Secure the airway (e.g., intubate) if GCS < 8, the patient has intractable seizures, or there are signs of cerebral herniation.
- Hemodynamic support with fluids and/or vasopressors (see fluid resuscitation and sepsis).
- Identify and reverse any coagulopathy (see disseminated intravascular coagulation).
- Identify and treat elevated ICP.
- The choice of initial empiric therapy depends primarily on the prevalence of organisms in certain age groups and individual patient risk factors for resistant organisms.
- Factors to consider:
|Empiric antibiotic therapy for bacterial meningitis |
|Patient characteristics||Recommended regimen|
Age < 1 month
|Age > 1 month to < 50 years|
|Age > 50 years|
|Healthcare-associated infections |
Suspected rickettsial (e.g., RMSF) or ehrlichial infection 
|Basilar skull fracture|
|Penetrating head trauma|
Ampicillin is added if patients are at risk of Listeria spp. infection (e.g., newborns, pregnant women, the elderly, or immunocompromised patients) because cephalosporins are ineffective against Listeria spp.
Empiric therapy for viral meningitis 
Most cases of viral meningitis (e.g., caused by enteroviruses) can be treated supportively. Specific antiviral therapy is only warranted if viral encephalitis is also suspected (see HSV encephalitis for further details).
- Concern for HSV encephalitis, for example:
- Risk factors (e.g., neonates with a mother who has active genital HSV lesions)
- Suggestive clinical features (e.g., focal neurological deficits, altered mental status; , seizures, behavioral changes, coma)
- Imaging findings (e.g., temporal lobe enhancement)
- CSF: ↑ RBCs despite a nontraumatic LP (suggestive of hemorrhagic encephalitis)
- Concern for other herpesviruses, e.g., VZV, EBV
- Concern for HSV encephalitis, for example:
Recommended empiric antiviral agent: acyclovir
- Continue treatment if either HSV or VZV is detected, otherwise discontinue.
Treatment with acyclovir should be started in all patients who present with typical clinical signs of viral meningoencephalitis and only discontinued after PCR and antibody tests are negative for HSV and VZV, even if CSF is initially normal.
The decision to narrow therapy should be guided by final culture and sensitivity results, as well as local resistance patterns. We list a few examples of antimicrobial agents that may be used against specific pathogens.
|Pathogen-specific therapy in meningitis |
|Pathogen||Examples of antimicrobial agents|
S. pneumoniae (penicillin-resistant strains)
|L. monocytogenes|| |
|P. aeruginosa|| |
|Less frequent pathogens, e.g., M. tuberculosis, C. neoformans, B. burgdorferi|| |
- Indication: suspected or proven meningitis due to S. pneumoniae or H. influenzae in adults and children
- Mechanism: reduces the local and systemic inflammation seen in bacterial meningitis and improves outcomes
- Recommended agent: dexamethasone for 2–4 days 
- Disadvantages: side effects, e.g., hyperglycemia, GI bleeding 
Monitoring and disposition
- Most patients with meningitis require admission; select patients may be considered for outpatient therapy with close follow-up. 
- Serial neuro examinations
- Infectious disease
- Consider also ICU , neurology, neurosurgery as needed.
- Stabilize the patient and obtain IV access
- Identify and treat sepsis, if present.
- Obtain blood cultures (two sets) and routine laboratory studies (e.g., CBC, coagulation studies, CRP).
- Consider indications for imaging prior to LP (i.e., presence of any criteria for imaging prior to LP in suspected meningitis)
- Perform LP and order CSF analysis if there are no contraindications
- Begin empiric antibiotics and steroids as soon as possible (see empiric antibiotic therapy for bacterial meningitis). 
- Consider empiric viral coverage.
- Provide supportive therapy as needed.
- Admit to medicine or neurology service.
- Ensure 24 hours of droplet isolation for all patients suspected of having bacterial meningitis.
- Consider indications for prophylactic treatment (see postexposure chemoprophylaxis for bacterial meningitis).
- Consult infectious diseases.
- Consult ICU, neurology, neurosurgery as needed.
- Pathogen: Mycobacterium tuberculosis
- Incubation period: approximately 2–8 weeks
- Subacute course over several weeks or months
- Gradual manifestation with intermittent fever
- Clinical features
- Treatment: see “Treatment” in
- Pathogen: Cryptococcus neoformans (a type of encapsulated yeast)
- Exposure to pigeon droppings
- Clinical course: subacute onset with (low) fever, fatigue, and headaches
- See section on “Clinical features” above
- Meningeal symptoms are often absent
Cryptococcal antigen testing of CSF and serum
- Highly specific and sensitive 
- Typically performed via latex agglutination or enzyme immunoassay
- CSF culture (Sabouraud agar)
- CSF gram staining: India Ink (clear halo), mucicarmine (red inner capsule)
- MRI: gelatinous pseudocysts (soap bubble appearance)
- Cryptococcal antigen testing of CSF and serum
Eurasia: Tick-borne meningoencephalitis
- Pathogen: tick-borne encephalitis virus (TBEV)
Route of infection: tick-borne
- Ixodid tick acts as a vector; therefore, transmission is predominantly in June/July and September/October.
- Occasional transmission via unpasteurized dairy products from infected livestock
- Incubation period: usually 7–14 days
- Clinical features:
- Treatment: symptomatic
- Full recovery is common (particularly in children and adolescents).
- In symptomatic disease, residual symptoms may occur.
Prevention: A vaccine is not available in the US.
- Active immunization with an inactivated TBEV (inactivated vaccination): Large-scale implementation of this vaccination is not generally recommended.
- The CDC's Advisory Committee on Immunization Practices (ACIP) recommends the vaccination only for individuals living, traveling, or working in high-risk areas (laboratory staff exposed to TBEV, foresters, etc.).
- Pathogen: Naegleria fowleri (colloquially referred to as “brain-eating amoeba”), found in warm freshwater (e.g., ponds, hot springs)
- Route of infection: via contaminated water entering the nose (e.g., while swimming) → invades the CNS directly via the cribriform plate
- Clinical features: causes fulminant meningoencephalitis with rapid onset
- Treatment: amphotericin B, miltefostine
- Prognosis: nearly always fatal