Bacterial Meningitis
Bacterial meningitis remains one of the most critical neurological emergencies, with mortality rates of 15–25% even with appropriate treatment and significant morbidity among survivors. The cornerstone of management is early recognition and immediate empiric antibiotic therapy — delays of even one hour are associated with increased mortality. The microbiology varies predictably by age and immune status, enabling targeted empiric regimens. Adjunctive dexamethasone has been shown to improve outcomes in pneumococcal meningitis in high-income settings. Neurologists must be adept at recognizing atypical presentations, interpreting CSF profiles, and managing the spectrum of neurological complications.
Bottom Line
- Do not delay antibiotics: Empiric therapy must be administered within 1 hour of presentation — do not wait for LP results or CT imaging
- Classic triad is unreliable: Headache, fever, and neck stiffness are all present in only ~45% of cases; altered mental status is the most sensitive individual sign (~70%)
- S. pneumoniae is #1 in adults: Most common organism across all adult age groups; N. meningitidis is second; add Listeria coverage (ampicillin) for age ≥50 or immunocompromised
- Dexamethasone timing is critical: Give before or with the first dose of antibiotics — not after; proven benefit in pneumococcal meningitis (de Gans 2002)
- CT before LP criteria: Immunocompromised, history of CNS disease, new-onset seizures, papilledema, altered consciousness, or focal neurologic deficit — but draw blood cultures and start antibiotics before sending to CT
- CSF pattern: Neutrophilic pleocytosis, elevated protein, low glucose (CSF:serum ratio <0.4), and elevated opening pressure; Gram stain positive in 60–90%
Epidemiology and Microbiology
The causative organisms in bacterial meningitis follow a predictable pattern based on patient age and immune status. Understanding this distribution is essential for selecting appropriate empiric therapy.
| Age Group | Most Common Organisms | Key Considerations |
|---|---|---|
| Neonates (<1 month) | Group B Streptococcus (GBS), E. coli K1, Listeria monocytogenes | Vertical transmission; GBS early-onset vs. late-onset |
| Infants (1–23 months) | S. pneumoniae, N. meningitidis, GBS, E. coli, H. influenzae type b | Hib rare since vaccination; pneumococcal serotypes shifting post-PCV13 |
| Children (2–18 years) | N. meningitidis, S. pneumoniae | Meningococcal outbreaks in dormitories; petechial rash suggestive |
| Adults (18–50 years) | S. pneumoniae (#1), N. meningitidis | Pneumococcal accounts for ~50% of adult cases |
| Older adults (≥50 years) | S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli | Listeria risk increases with age; add ampicillin to empiric regimen |
| Immunocompromised | S. pneumoniae, L. monocytogenes, gram-negative bacilli, Cryptococcus | Broader differential; consider fungal and tuberculous etiologies |
In the post-vaccination era, the epidemiology has shifted significantly. Haemophilus influenzae type b meningitis has declined by >99% in countries with routine Hib vaccination. S. pneumoniae remains the leading cause of bacterial meningitis in adults in developed countries, accounting for approximately 50% of cases. Mortality rates vary by organism: ~20–30% for pneumococcal, ~5–10% for meningococcal, and ~20–30% for Listeria meningitis.
Clinical Presentation
The clinical manifestations of bacterial meningitis reflect meningeal inflammation and its consequences. The presentation may be acute (hours) or subacute (days), and can be modified by prior antibiotic use.
Signs and Symptoms
- Classic triad: Headache, fever, and neck stiffness — present together in only ~45% of cases
- Altered mental status: The most sensitive individual sign, present in ~70% of cases; ranges from lethargy to coma
- Headache: Present in ~85% of cases; typically severe, generalized, and progressive
- Fever: Present in ~80–95% of cases; may be absent in the elderly or immunocompromised
- Neck stiffness (nuchal rigidity): Present in ~70% of cases; may be absent early in the disease course
- Nausea and vomiting: Common (~35%); reflects increased intracranial pressure
- Photophobia: Frequently reported; indicative of meningeal irritation
- Seizures: Occur in 20–30% of patients; more common with pneumococcal meningitis
Meningeal Signs on Examination
- Kernig sign: With hip flexed to 90°, pain or resistance to passive knee extension — sensitivity ~5%, specificity ~95%
- Brudzinski sign: Passive neck flexion causes involuntary hip and knee flexion — sensitivity ~5%, specificity ~95%
- Jolt accentuation test: Worsening of headache with horizontal rotation of the head 2–3 times per second — most sensitive bedside test (sensitivity ~97%, specificity ~60%); a negative result makes meningitis unlikely
- Nuchal rigidity: Resistance to passive neck flexion — sensitivity ~30%, specificity ~70%
- Key point: Classic meningeal signs (Kernig, Brudzinski) have poor sensitivity but high specificity; their absence does not rule out meningitis
Red Flags for Meningococcal Disease
- Petechial or purpuric rash: Present in 50–80% of meningococcal meningitis; may progress to purpura fulminans
- Rapidly progressive course: Can deteriorate from well-appearing to moribund within hours
- Waterhouse-Friderichsen syndrome: Bilateral adrenal hemorrhage with septic shock — catastrophic complication of meningococcemia
- Any febrile patient with new petechiae: Must be treated as possible meningococcal disease until proven otherwise
Diagnostic Approach
When to Image Before Lumbar Puncture
The 2004 IDSA guidelines established clear criteria for when CT should precede LP. However, the critical principle is that antibiotics should never be delayed for imaging. Blood cultures should be drawn and empiric therapy started before the patient leaves for CT.
| CT Before LP Indications (IDSA 2004) | Rationale |
|---|---|
| Immunocompromised state (HIV/AIDS, immunosuppressive therapy, transplant) | Risk of mass lesion (toxoplasmosis, lymphoma, abscess) |
| History of CNS disease (mass lesion, stroke, focal infection) | Pre-existing structural lesion may cause herniation |
| New-onset seizure (within 1 week) | May indicate focal pathology with mass effect |
| Papilledema on fundoscopy | Indicates elevated intracranial pressure |
| Altered level of consciousness | Suggests diffuse cerebral edema or focal pathology |
| Focal neurologic deficit (excluding cranial nerve palsy) | Suggests focal mass lesion |
Critical Management Sequence
- If NO indication for CT before LP: Blood cultures → LP → Empiric antibiotics + dexamethasone (within 1 hour of arrival)
- If CT indicated before LP: Blood cultures → Empiric antibiotics + dexamethasone → CT → LP (if safe)
- Never delay antibiotics for CT, LP, or any other test — each hour of delay increases mortality
- A normal CT does not exclude elevated ICP; clinical judgment is still required
CSF Analysis
The CSF profile in bacterial meningitis has a characteristic pattern, though there is overlap with other etiologies, particularly in partially treated cases or early presentations.
| CSF Parameter | Bacterial Meningitis | Viral Meningitis | Tuberculous Meningitis | Fungal Meningitis |
|---|---|---|---|---|
| Opening pressure | >25 cm H2O (often >30) | Normal to mildly ↑ | ↑ | ↑ (often markedly in Cryptococcus) |
| WBC count | 1,000–10,000/μL | 50–1,000/μL | 100–500/μL | 20–500/μL |
| Cell predominance | >80% neutrophils | Lymphocytes (early may be PMN) | Lymphocytes | Lymphocytes |
| Protein | >100 mg/dL (often >200) | 50–100 mg/dL | 100–500 mg/dL | 50–300 mg/dL |
| Glucose | <40 mg/dL (ratio <0.4) | Normal | ↓ (ratio <0.5) | ↓ |
| Gram stain sensitivity | 60–90% | N/A | 10–20% (AFB) | Variable (India ink ~50%) |
Additional CSF Diagnostics
- Gram stain: Positive in 60–90% of untreated cases; sensitivity varies by organism (90% for S. pneumoniae, 75% for N. meningitidis, 50% for gram-negative bacilli)
- Culture: Gold standard; positive in 70–85% of untreated cases; sensitivity drops significantly after antibiotics
- Latex agglutination: Rapid but limited sensitivity; largely supplanted by PCR
- Multiplex PCR panels (e.g., BioFire FilmArray): Rapid (~1 hour); detects common bacterial, viral, and fungal pathogens; particularly useful in pretreated patients
- CSF lactate: ≥3.5 mmol/L suggests bacterial etiology (sensitivity ~93%, specificity ~96%); useful in post-neurosurgical meningitis
- Procalcitonin (serum): ≥0.5 ng/mL supports bacterial meningitis over viral; useful as adjunctive marker
Treatment
Empiric Antibiotic Therapy
Empiric therapy must be initiated immediately and tailored once culture and sensitivity results are available. The choice of empiric regimen is driven by the patient's age, immune status, and local resistance patterns.
| Patient Group | Empiric Regimen | Rationale |
|---|---|---|
| Neonates (<1 month) | Ampicillin + cefotaxime (or gentamicin) | Covers GBS, E. coli, Listeria |
| Infants/Children (1 month–18 years) | Vancomycin + ceftriaxone (or cefotaxime) | Covers pneumococcus (including penicillin-resistant) + meningococcus |
| Adults (18–49 years) | Vancomycin + ceftriaxone | Covers pneumococcus (including resistant strains) + meningococcus |
| Adults ≥50 years or immunocompromised | Vancomycin + ceftriaxone + ampicillin | Adds Listeria coverage |
| Post-neurosurgical / penetrating trauma | Vancomycin + cefepime (or meropenem) | Covers staphylococci and hospital-acquired gram-negatives including Pseudomonas |
Adjunctive Dexamethasone
The landmark trial by de Gans and van de Beek (NEJM, 2002) demonstrated that adjunctive dexamethasone (0.15 mg/kg IV every 6 hours for 4 days) significantly reduced unfavorable outcomes and mortality in adults with bacterial meningitis, particularly pneumococcal meningitis.
Dexamethasone Recommendations
- Timing: Must be given before or simultaneously with the first dose of antibiotics — no proven benefit if given after antibiotics have already been administered
- Dose: 0.15 mg/kg IV every 6 hours for 4 days (adult dose: typically 10 mg IV q6h)
- Strongest evidence: Pneumococcal meningitis in adults in high-income countries — reduced mortality from 34% to 14% in the de Gans trial
- Hearing loss: Significantly reduced in pneumococcal meningitis with dexamethasone
- Discontinue if: Non-pneumococcal organism identified (though some guidelines recommend continuing for all bacterial etiologies)
- Pediatric data: Most benefit demonstrated for H. influenzae type b meningitis (reduced hearing loss); less clear benefit for other organisms in children
- Concern: Dexamethasone may reduce vancomycin CSF penetration — some experts recommend adding rifampin if pneumococcal resistance suspected
Pathogen-Directed Therapy and Duration
| Organism | Preferred Therapy | Duration | Notes |
|---|---|---|---|
| S. pneumoniae (penicillin-sensitive, MIC <0.06) | Penicillin G or ampicillin | 10–14 days | Narrow once susceptibilities known |
| S. pneumoniae (penicillin-resistant) | Vancomycin + ceftriaxone | 10–14 days | Add rifampin if ceftriaxone MIC ≥2 |
| N. meningitidis | Penicillin G or ceftriaxone | 7 days | Droplet precautions for 24 hours after antibiotics |
| L. monocytogenes | Ampicillin ± gentamicin | ≥21 days | Cephalosporins are not active against Listeria |
| H. influenzae | Ceftriaxone | 7 days | Check β-lactamase production |
| GBS (neonatal) | Ampicillin + gentamicin | 14–21 days | Longer courses for complicated cases |
| Gram-negative bacilli | Ceftriaxone or cefepime or meropenem | 21 days | Susceptibility-guided; consider intrathecal aminoglycosides in refractory cases |
Complications
Neurological complications are common in bacterial meningitis and significantly impact outcomes. Close monitoring is essential, particularly in the first 48–72 hours.
| Complication | Frequency | Mechanism | Management |
|---|---|---|---|
| Cerebral edema | Common | Vasogenic and cytotoxic edema from inflammation | Head elevation, osmotherapy (mannitol/hypertonic saline), dexamethasone |
| Hydrocephalus | 5–15% | Communicating (impaired CSF absorption) or obstructive | EVD or VP shunt if persistent; may need serial LPs |
| Seizures | 20–30% | Cortical irritation, ischemia, electrolyte abnormalities | Antiseizure medications; continuous EEG if altered consciousness |
| Cerebral venous thrombosis | 5–10% | Inflammation of cortical veins and sinuses | Anticoagulation if no hemorrhagic contraindication; monitor with MRV |
| Stroke (arterial) | 15–20% | Vasculitis, vasospasm; especially basal arteries | Supportive; role of anti-inflammatory therapy uncertain |
| Subdural effusion/empyema | 5–10% | Contiguous spread from meningeal infection | Empyema requires urgent surgical drainage |
| Hearing loss (sensorineural) | 10–30% | Labyrinthitis, cochlear nerve damage | Dexamethasone reduces risk; audiometry at follow-up |
| Cranial nerve palsies | 5–15% | Inflammatory involvement at skull base | Usually resolves with treatment; CN VIII most common |
Prevention
Chemoprophylaxis for Meningococcal Disease
Close contacts of patients with meningococcal meningitis should receive prophylaxis as soon as possible (ideally within 24 hours of diagnosis of the index case). Close contacts include household members, daycare contacts, and anyone directly exposed to the patient's oral secretions in the 7 days before symptom onset.
| Agent | Dose | Duration | Notes |
|---|---|---|---|
| Rifampin | 600 mg PO q12h (adults); 10 mg/kg q12h (children) | 2 days (4 doses) | Drug interactions (OCP, warfarin); turns secretions orange |
| Ciprofloxacin | 500 mg PO single dose (adults) | Single dose | Most convenient; avoid in pregnancy |
| Ceftriaxone | 250 mg IM single dose (adults); 125 mg IM (<15 years) | Single dose | Preferred in pregnancy |
Vaccination
Vaccine Recommendations
- Pneumococcal vaccines: PCV15 or PCV20 for all adults ≥65 or those with risk factors (asplenia, immunocompromise, CSF leaks, cochlear implants); reduces invasive pneumococcal disease by 60–80%
- Meningococcal conjugate vaccine (MenACWY): Routine for adolescents at 11–12 years with booster at 16; required for college dormitory entry in many states; recommended for asplenia, complement deficiency, HIV, travelers to endemic areas
- Meningococcal serogroup B vaccine (MenB): Shared clinical decision-making for 16–23 year-olds; recommended for those at increased risk (complement deficiency, eculizumab use, asplenia, outbreaks)
- Post-splenectomy patients: Should receive both pneumococcal and meningococcal vaccines; also need H. influenzae type b vaccine
- CSF leak or cochlear implant: Pneumococcal vaccination strongly recommended due to recurrent meningitis risk
Special Considerations
Partially Treated Meningitis
Prior oral antibiotics (e.g., prescribed for a presumed URI) can modify the CSF profile, making diagnosis more difficult. CSF may show lower WBC counts, partially cleared Gram stain, and negative cultures. Multiplex PCR panels retain sensitivity in this setting and are invaluable.
Recurrent Bacterial Meningitis
- Anatomic defects: CSF leak from basilar skull fracture, cribriform plate defect, or congenital inner ear abnormality (most common cause of recurrent meningitis)
- Complement deficiency: Terminal complement pathway deficiencies (C5–C9) predispose to recurrent Neisseria infections; screen with CH50
- Asplenia: Risk of overwhelming post-splenectomy infection with encapsulated organisms
- Evaluation: High-resolution CT of temporal bones and skull base; immunologic workup including complement levels and immunoglobulin levels
Healthcare-Associated Meningitis
Post-neurosurgical or device-related meningitis (EVD, VP shunt) requires coverage of staphylococci (including MRSA) and gram-negative organisms including Pseudomonas. Empiric regimen: vancomycin + cefepime or meropenem. Intrathecal or intraventricular vancomycin (or gentamicin) may be necessary for refractory infections. Device removal is often required for cure.
Prognosis and Follow-Up
- Mortality: Overall 15–25% with treatment; highest for pneumococcal (~25–30%) and Listeria (~20–30%); lowest for meningococcal (~5–10%)
- Long-term sequelae: 30–50% of survivors have neurologic sequelae — hearing loss, cognitive deficits, focal deficits, epilepsy
- Audiometry: Recommended for all survivors, especially pneumococcal meningitis
- Repeat LP: Not routinely indicated if clinically improving; consider if no improvement by 48–72 hours or if resistant organism suspected
- Cognitive rehabilitation: Many survivors benefit from neuropsychological assessment and cognitive rehabilitation
References
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