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Meningitis: A Comprehensive Overview

Meningitis is inflammation of the meninges (pia, arachnoid, and dura mater) surrounding the brain and spinal cord. It is classified by cause, time course, and pathogen type. Bacterial meningitis is a medical emergency with significant mortality and morbidity if untreated promptly.

1. Etiology and Classification

Bacterial (Acute Pyogenic)

The most common and most dangerous form. Key pathogens vary by age and setting:

Population	Common Organisms
Neonates	Group B Streptococcus, E. coli, Listeria monocytogenes
Children/Adults (community)	S. pneumoniae, N. meningitidis
Adults >50 / immunocompromised	S. pneumoniae, L. monocytogenes, gram-negative bacilli
Post-neurosurgery	Staphylococci, gram-negative bacilli (Pseudomonas, Acinetobacter)
Sinusitis/Otitis-associated	S. pneumoniae, anaerobes

S. pneumoniae and N. meningitidis colonize the nasopharyngeal mucosa, gaining CNS entry hematogenously. L. monocytogenes is typically food-borne and disproportionately affects the elderly, diabetics, and the immunosuppressed. - Bradley and Daroff's Neurology in Clinical Practice, p. 1698

Viral (Aseptic Meningitis)

The most common type overall. The term "aseptic meningitis" refers to meningeal inflammation with no bacteria on culture. Enteroviruses (Coxsackievirus, Echovirus) are responsible for the vast majority of cases. Other causes include HSV-2, mumps, HIV, and arboviruses. Viral meningitis is generally self-limited and benign.

Chronic / Subacute

Tuberculous meningitis (TBM): the leading cause worldwide due to global Mycobacterium tuberculosis endemicity
Fungal: Cryptococcus neoformans (especially in HIV/immunocompromised patients), Coccidioides, Histoplasma
Spirochetal: Treponema pallidum (neurosyphilis), Borrelia burgdorferi (Lyme disease)

2. Clinical Features

The classic triad of fever + headache + neck stiffness (nuchal rigidity) is present in only about 44% of patients; however, nearly all patients have at least two of the four features: headache, fever, stiff neck, or altered mental status.

Additional signs:

Photophobia and phonophobia
Kernig's sign: inability to fully extend the knee when the hip is flexed at 90° (meningeal irritation)
Brudzinski's sign: passive flexion of the neck causes involuntary hip/knee flexion
Petechial/purpuric rash: characteristic of meningococcal meningitis - suggests disseminated intravascular coagulation (DIC) and demands immediate action
Seizures: occur in 20-30% of patients; more common with pneumococcal meningitis
Cranial nerve palsies: CN III, IV, VI, VII (seen in 5-10% of adults)
Papilledema: rare (<1%) in acute bacterial meningitis, but if present suggests a chronic process (fungal/TB) or complication (subdural empyema, abscess)

Waterhouse-Friderichsen Syndrome

Fulminant meningococcemia with bilateral adrenal hemorrhage, DIC, purpuric rash, and circulatory collapse - a life-threatening emergency.

3. CSF Analysis (Key Diagnostic Tool)

Lumbar puncture (LP) is the cornerstone of diagnosis. The CSF profile distinguishes different etiologies:

Type	Opening Pressure (cm H₂O)	WBC (cells/µL)	Protein (mg/dL)	Glucose (mg/dL)
Normal	10-20	<5	20-40	40-60
Bacterial	>20	>1000 (neutrophils)	>100	<10 (very low)
TB/Fungi	>20	100-500 (lymphocytes)	>100	10-45
Viral	<20	5-500 (lymphocytes)	50-150	Normal
Spirochetal (Lyme/Syphilis)	<20	5-500	50-150	10-45

Goldman-Cecil Medicine, Table 391-2

Key CSF tests:

Gram stain: positive in 60-80% of untreated bacterial cases; drops to 7-41% after antibiotics
Culture: gold standard; positive in 80-90% if obtained before or within 1-2 hours of first antibiotic dose
CSF glucose: bacterial meningitis characteristically shows a CSF:serum glucose ratio <0.4
Protein: typically >100 mg/dL in bacterial meningitis, often >200 mg/dL
CSF lactate: >3.0 mmol/L has 94-95% sensitivity/specificity for bacterial meningitis
PCR (meningitis/encephalitis panel): highly sensitive for S. pneumoniae, N. meningitidis, HSV, enteroviruses, Listeria; does not test susceptibility
Broad-range PCR: sensitivity 87-100%, specificity 98-100%; useful when cultures are negative
Tintinalli's Emergency Medicine, p. 1214; Goldman-Cecil Medicine, p. 4003

4. CT Before LP?

Obtain CT head before LP if any of the following are present:

Altered or deteriorating mental status
Focal neurologic deficit
New-onset seizure
Papilledema
Immunocompromised state / malignancy
History of focal CNS disease (stroke, tumor, abscess)
Age >60 years

A normal CT does not guarantee safe LP if clinical signs of impending herniation are present (posturing, irregular respirations, fixed dilated pupils). - Tintinalli's Emergency Medicine, Table 174-3

5. Treatment

Guiding Principle

Never delay antibiotics to wait for LP or CT. Door-to-antibiotic goal is <1 hour. It takes ~2 hours for antibiotics to sterilize CSF, so LP within that window remains valuable. - Goldman-Cecil Medicine, p. 4002

Empiric Antibiotic Regimens

Patient Profile	Empiric Regimen	Target Organisms
Immunocompetent adult (18-49 y)	Ceftriaxone 2g IV + Vancomycin 15-20 mg/kg IV	S. pneumoniae, N. meningitidis
Age >50 y / immunocompromised	Ceftriaxone 2g IV + Vancomycin + Ampicillin 2g IV	Above + L. monocytogenes
PCN allergy (severe)	Meropenem 2g IV or Moxifloxacin 400mg IV + TMP-SMX (for Listeria)	As above
Post-neurosurgery	Ceftazidime or Cefepime + Vancomycin	Staph, Pseudomonas, gram-negatives
Suspected HSV encephalitis	Add Acyclovir 10 mg/kg IV	HSV

Tintinalli's Emergency Medicine, Table 174-4

Adjunctive Corticosteroids

Dexamethasone 10 mg IV every 6 hours for 3 days, given just before or with the first antibiotic dose
Reduces CSF inflammation, mortality in adults, and hearing loss in children with pneumococcal meningitis
Can be given up to 4 hours after antibiotics are started if not already given

Viral Meningitis

Supportive care (analgesia, antipyretics, hydration) is the mainstay. No antiviral therapy is needed for enteroviral meningitis. Acyclovir is added if HSV is suspected.

Tuberculous Meningitis

A 2026 Lancet Infectious Diseases practice guideline provides updated recommendations. Standard treatment is a 4-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol) with adjunctive dexamethasone.

6. Complications

Sensorineural hearing loss - most common neurologic sequela; due to spread of infection/toxins along the cochlear aqueduct
Cerebral edema with transtentorial herniation (cause of death in ~25% of fatal cases)
Seizures (20-30%)
Hydrocephalus (communicating or obstructive)
Cerebral infarction from arterial/venous thrombosis
Subdural empyema or effusion
SIADH with hyponatremia
DIC (especially meningococcal disease)
Cognitive and behavioral sequelae in children

7. Prevention (Vaccination)

Major strides have been made through vaccination:

Hib (H. influenzae type b) vaccine: dramatically reduced pediatric bacterial meningitis
Pneumococcal vaccines (PCV13, PPSV23): reduced meningitis and otitis media in children
Meningococcal glycoconjugate vaccine (MenACWY): covers serogroups A, C, W-135, Y; does not provide lasting immunity or cover serogroup B
MenB vaccine: separate vaccine for serogroup B; now required for most university students in the US
BCG vaccination reduces risk of TB meningitis in children
Bradley and Daroff's Neurology in Clinical Practice, p. 1698

Recent Literature (2024-2026)

A 2026 Lancet ID clinical practice guideline for tuberculous meningitis (Donovan et al.) provides updated evidence-based recommendations for TBM management
A 2025 systematic review in JAMA Neurology on IgG4-related pachymeningitis characterizes presentation and outcomes of this rare autoimmune variant
A 2026 meta-analysis in JAMA assessed prediction of bacteremia and bacterial meningitis in febrile infants ≤28 days, with implications for neonatal workup

Sources: Bradley and Daroff's Neurology in Clinical Practice | Goldman-Cecil Medicine (International Edition) | Tintinalli's Emergency Medicine | Textbook of Family Medicine 9e | Henry's Clinical Diagnosis and Management by Laboratory Methods

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