Bacterial Meningitis
Acute pyogenic infection of the meninges — neurologic emergency requiring empiric antibiotics within 1 hour.
Also known as: bacterial meningitis, meningococcal meningitis, pneumococcal meningitis, acute meningitis
Overview
Acute pyogenic infection of the leptomeninges and subarachnoid space, characterized by inflammation, neutrophilic CSF pleocytosis, and high morbidity/mortality without prompt antibiotic therapy.
Epidemiology
Incidence in the US ~1-2 per 100,000 adults annually; higher in infants and young children. Vaccination has dramatically reduced Haemophilus influenzae type b and Streptococcus pneumoniae meningitis. Outbreaks of Neisseria meningitidis occur in close-contact settings (college dormitories, military barracks).
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Risk factors
- Age extremes (<2 years, >65 years)
- Immunocompromise: HIV, asplenia (encapsulated organisms), complement deficiency (recurrent Neisseria), corticosteroids, transplant, hematologic malignancy
- Recent neurosurgery, head trauma with CSF leak, basilar skull fracture
- Cochlear implants
- Otitis media, mastoiditis, sinusitis, endocarditis (contiguous or hematogenous spread)
- Crowded living (dorms, military, prison) — Neisseria meningitidis
- Unvaccinated status
- Alcohol use disorder, diabetes, cirrhosis
Pathophysiology
Most cases arise from nasopharyngeal colonization → bacteremia → seeding of the choroid plexus and meninges. Bacterial cell wall components (LPS, peptidoglycan) trigger massive cytokine release (TNF, IL-1, IL-6), neutrophil influx, increased blood-brain barrier permeability, cerebral edema, increased intracranial pressure, decreased cerebral blood flow, and neuronal injury. Vasculitis can cause cortical infarcts and cranial neuropathies (especially CN VIII → hearing loss).
Clinical presentation
Symptoms
- Classic triad (only ~44% have all 3): fever, neck stiffness, altered mental status
- ≥95% have at least 2 of 4: fever, headache, neck stiffness, AMS
- Severe headache, photophobia, nausea/vomiting
- Seizures (~15-30%)
- Petechial/purpuric rash (Neisseria meningitidis — purpura fulminans suggests meningococcemia and is highly suggestive)
- Cranial neuropathies (especially CN VI, VII, VIII)
- Infants: poor feeding, irritability, bulging fontanelle, hypothermia or fever, hypotonia — meningismus often absent
Signs / physical exam
- Fever, tachycardia, hypotension (in sepsis)
- Nuchal rigidity
- Kernig sign: pain with passive knee extension when hip flexed
- Brudzinski sign: involuntary hip/knee flexion when neck flexed
- Jolt accentuation: worsening headache with horizontal head rotation 2-3 Hz (more sensitive)
- Altered mental status, focal neurologic deficits
- Petechiae over trunk/extremities (meningococcal)
- Look for sources: otitis, mastoiditis, sinus tenderness, endocarditis, CSF leak
Classic findings
Fever + meningismus + altered mental status; petechiae suggest meningococcemia.
Differential diagnosis
- Viral (aseptic) meningitis — Less ill-appearing; lymphocytic CSF, normal glucose, mildly elevated protein, negative gram stain; enterovirus most common
- Encephalitis (HSV, arboviral) — Prominent altered mental status, seizures, focal deficits; HSV with temporal lobe involvement on MRI
- Subarachnoid hemorrhage — Thunderclap headache; LP with RBCs and xanthochromia; CT head before LP if clinical suspicion
- Brain abscess — Focal deficits, ring-enhancing lesion on imaging; LP often contraindicated due to mass effect
- Tuberculous meningitis — Subacute course (1-2 weeks), basilar meningitis, cranial nerve palsies, lymphocytic CSF with high protein, very low glucose, AFB smear/PCR/culture
- Cryptococcal meningitis — Immunocompromised (HIV CD4<100), subacute headache, India ink positive, CrAg+, elevated opening pressure
- Carcinomatous / lymphomatous meningitis — Known malignancy, chronic course, malignant cells on cytology
- Drug-induced aseptic meningitis — NSAIDs, TMP-SMX, IVIG; symptoms resolve after drug withdrawal
Diagnostic workup
Diagnostic criteria
Acute clinical syndrome (fever, headache, meningismus, AMS) + CSF profile consistent with bacterial meningitis (neutrophilic pleocytosis, low glucose, elevated protein) ± positive Gram stain or culture.
Labs
- Blood cultures x 2 BEFORE antibiotics (do not delay antibiotics for blood draw)
- CBC, BMP, coagulation, lactate, glucose, procalcitonin
- LP CSF studies: opening pressure, cell count and differential, protein, glucose (with simultaneous serum glucose), Gram stain, culture, latex agglutination/multiplex PCR (meningitis/encephalitis panel), HSV PCR, cryptococcal antigen if at risk, AFB stain/culture/PCR if TB suspected, cytology in older patients
- Typical bacterial CSF: WBC >1000 (PMN predominant), glucose <40 (or CSF:serum ratio <0.4), protein >200, opening pressure elevated (>250 mm H2O)
Imaging
- CT head BEFORE LP only if any of: immunocompromise, history of CNS disease (mass, stroke, focal infection), new seizure within 1 week, papilledema, abnormal level of consciousness, focal neurologic deficit, age >60 — to exclude mass effect and risk of herniation
- DO NOT delay antibiotics for imaging or LP — give empiric antibiotics immediately if any delay anticipated
- MRI brain if focal findings, suspected complications (abscess, ventriculitis, infarct)
Diagnostic algorithm
| Parameter | Bacterial | Viral | Fungal/TB | Normal |
|---|---|---|---|---|
| Opening pressure (mm H2O) | Elevated (>250) | Normal or mildly elevated | Elevated | 70-180 |
| WBC (cells/µL) | >1000 (often 1000-5000) | 10-500 | 100-500 | 0-5 |
| WBC predominance | Neutrophils (PMN) | Lymphocytes | Lymphocytes | — |
| Glucose (mg/dL) | Low (<40) or CSF:serum <0.4 | Normal | Low | 50-80 (~2/3 serum) |
| Protein (mg/dL) | High (>200) | Mildly elevated (50-150) | Very high (>250) | <45 |
| Gram stain | Often positive | Negative | Negative (AFB/India ink) | Negative |
Treatment
First-line
- Empiric antibiotics within 1 hour of presentation — do not delay for imaging or LP if not immediately available:
- Adults 18-50: ceftriaxone 2 g IV q12h + vancomycin 15-20 mg/kg IV q8-12h (covers pneumococcus with ceftriaxone resistance)
- Adults >50 or immunocompromised, alcoholic, pregnant: ADD ampicillin 2 g IV q4h to cover Listeria monocytogenes
- Neonates (<1 month): ampicillin + cefotaxime (or gentamicin) — covers GBS, E. coli, Listeria
- Children 1 month-18 years: ceftriaxone + vancomycin
- Post-neurosurgery/penetrating head trauma: vancomycin + cefepime (or ceftazidime or meropenem) — covers Pseudomonas, MRSA, gram-negatives
- Dexamethasone 0.15 mg/kg IV q6h x 4 days, FIRST DOSE 10-20 minutes BEFORE OR WITH first antibiotic dose — reduces mortality and neurologic sequelae (especially hearing loss) in pneumococcal meningitis (de Gans & van de Beek NEJM 2002); continue if pneumococcus confirmed
- Acyclovir IV 10 mg/kg q8h if HSV encephalitis cannot be excluded
Second-line / adjunct
- Narrow antibiotics once Gram stain/culture/sensitivities return:
- S. pneumoniae (gram-positive diplococci): ceftriaxone (continue vancomycin until sensitivities confirm)
- N. meningitidis (gram-negative diplococci): ceftriaxone or penicillin G
- H. influenzae (gram-negative coccobacilli): ceftriaxone
- L. monocytogenes (gram-positive rods): ampicillin ± gentamicin
- Group B Streptococcus: penicillin G or ampicillin
- Standard duration: meningococcus 7 days, H. influenzae 7-10 days, pneumococcus 10-14 days, GBS 14-21 days, Listeria 21 days, gram-negative bacilli 21 days
- Chemoprophylaxis for close contacts of meningococcus: rifampin 600 mg PO BID x 2 days, ciprofloxacin 500 mg PO x 1, or ceftriaxone 250 mg IM x 1 (preferred in pregnancy)
- Vaccinate close contacts of vaccine-preventable cases (meningococcal, Hib, pneumococcal); update routine vaccinations in survivors and high-risk patients
- Audiology screening on recovery (CN VIII injury, especially pneumococcal)
Complications
- Death (mortality ~10-30% adults; up to 50% pneumococcal in elderly)
- Sensorineural hearing loss (~10-30%, especially pneumococcal)
- Cognitive impairment, memory deficits
- Seizure disorder
- Cranial nerve palsies
- Hydrocephalus, cerebral infarction
- Subdural empyema, brain abscess
- Septic shock, DIC, adrenal hemorrhage (Waterhouse-Friderichsen with meningococcemia)
- Limb necrosis from purpura fulminans
PANCE pearls
- Empiric antibiotics within 1 hour. If CT before LP is needed, give blood cultures and antibiotics FIRST.
- Add ampicillin for Listeria in patients >50, immunocompromised, alcoholic, or pregnant.
- Dexamethasone before/with first antibiotic in suspected pneumococcal meningitis — reduces mortality and hearing loss.
- Petechial rash with meningismus = meningococcemia until proven otherwise; isolate, treat, and notify public health.
- Vaccination: MenACWY (preteens, college students, military, asplenia, complement deficiency); MenB (high-risk patients and during outbreaks); PCV13/15/20 and PPSV23; Hib in children.
- Close contacts of meningococcus require chemoprophylaxis within 24 hours.
- In suspected partially treated meningitis (prior antibiotics), Gram stain and culture may be negative — multiplex PCR helpful.
- Recurrent meningitis suggests anatomic defect (CSF leak from basilar skull fracture, dermal sinus tract) or complement deficiency.
References
- IDSA 2004 — Practice Guidelines for the Management of Bacterial Meningitis (Tunkel et al., Clin Infect Dis 2004; updates pending)
- ESCMID 2016 — Diagnosis and Treatment of Acute Community-Acquired Bacterial Meningitis (van de Beek et al., Clin Microbiol Infect 2016)
- de Gans NEJM 2002 — Dexamethasone in Adults with Bacterial Meningitis (de Gans & van de Beek, NEJM 2002)
- CDC ACIP — ACIP Recommendations for Meningococcal Vaccination
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