Neurology · PANCE / PANRE

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

ParameterBacterialViralFungal/TBNormal
Opening pressure (mm H2O)Elevated (>250)Normal or mildly elevatedElevated70-180
WBC (cells/µL)>1000 (often 1000-5000)10-500100-5000-5
WBC predominanceNeutrophils (PMN)LymphocytesLymphocytes
Glucose (mg/dL)Low (<40) or CSF:serum <0.4NormalLow50-80 (~2/3 serum)
Protein (mg/dL)High (>200)Mildly elevated (50-150)Very high (>250)<45
Gram stainOften positiveNegativeNegative (AFB/India ink)Negative
Typical CSF profiles by etiology of meningitis.

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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