Acute Meningitis¶
Chapter 143 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 143
Key Clinical Points¶
- Classic triad of fever, headache, and nuchal rigidity occurs in >80% of adult cases.
- Dexamethasone (10 mg IV q6h) should precede or coincide with first antibiotic dose to reduce mortality and hearing loss.
- Empirical therapy for community-acquired cases: vancomycin + third-/fourth-generation cephalosporin (ceftriaxone, ceftriaxome, cefepime).
- Acyclovir added if HSV encephalitis is suspected.
- CSF findings of bacterial meningitis: PMN >100 cells/μL, glucose <2.2 mmol/L (<40 mg/dL), protein >0.45 g/L (>45 mg/dL).
- CSF/serum glucose ratio <0.4 is highly suggestive of bacterial etiology.
- Listeria monocytogenes requires ampicillin in neonates, pregnant women, and adults >50 years.
- Mortality varies by pathogen: 3–7% for H. influenzae/N. meningitidis/GBS; 20% for S. pneumoniae.
- Meningococcal contacts require chemoprophylaxis with rifampin, azithromycin, or ceftriaxone.
- Seizures occur in 15–40% of patients due to ischemia, venous thrombosis, or hyponatremia.
1. DEFINITION & OVERVIEW¶
• Bacterial Meningitis: An acute purulent infection within the subarachnoid space (SAS). • Clinical Impact: A CNS inflammatory reaction that may cause decreased consciousness, seizures, raised intracranial pressure (ICP), and stroke. • Involvement: The inflammatory response frequently involves the meninges, SAS, and brain parenchyma (meningoencephalitis).
2. INCIDENCE AND PREVALENCE¶
• US Incidence: ~1.4 cases/100,000 population. • Common Community-Acquired Pathogens: ◦ S. pneumoniae (~50%) ◦ N. meningitidis (~25%) ◦ Group B streptococci (~15%) ◦ L. monocytogenes (~10%) ◦ H. influenzae type b (<10%) • Trends: N. meningitidis incidence has decreased due to quadrivalent (A, C, W-135, Y) and serogroup B vaccines; a pentavalent vaccine (A, B, C, W-135, Y) is now available.
3. ETIOLOGY & PATHOPHYYSOLOGY¶
• Pathogen Entry: S. pneumoniae and N. meningitidis colonize the nasopharynx → enter bloodstream via epithelial cells or tight junctions. • Immune Evasion: Polysaccharide capsules allow evasion of phagocytosis and complement-mediated killing. • CNS Invasion: Bacteria reach CSF through choroid plexus or cerebral capillary endothelium → multiply due to lack of immune defenses. • Inflammatory Cascade (Figure 143-1): ◦ Release of bacterial cell-wall components (endotoxin, lactic acid) → Production of inflammatory cytokines (TNF-α, IL-1β). ◦ Cytokine effects include: → Altered blood-brain barrier permeability → protein leakage and exudate in SAS. → Adherence of leukocytes to cerebral endothelial cells → migration into CSF and release of toxic metabolites. → Alterations in cerebral blood flow → impacts oxygen/nutrient delivery. → Production of reactive oxygen species → cell injury and death. • Clinical Consequences: Vasogenic edema, obstructive and communicating hydrocephalus, cytotoxic edema, stroke, seizures, and increased ICP.
3.1 Etiologic Agents¶
• S. pneumoniae: Most common in adults >20 years; risk factors include pneumococcal pneumonia, alcoholism, diabetes, splenectomy. • N. meningitidis: Declined with vaccination; serogroup B vaccines do not reduce carriage. • L. monocytogenes: Important in neonates, pregnant women, and immunocompromised adults. • Gram-negative bacilli: Common in chronic diseases (diabetes, cirrhosis). • S. aureus: Associated with post-neurosurgical procedures or subcutaneous Ommaya reservoirs.
4. CLINICAL MANIFESTATIONS¶
• Presentation: Acute fulminant or subacute. • Classic Triad (found in >80% of adults): Fever, headache, and nuchal rigidity. • Additional Symptoms: Altered consciousness (>75%), nausea/vomiting, photophobia. • Physical Exam Signs: → Nuchal rigidity: resists passive flexion. → Kernig's sign: pain on knee extension. → Brudzinski's sign: hip/knee flexion with neck flexion (sensitivity/specificity uncertain; may be absent in young, elderly, or immunocompromised patients). • Intracranial Pressure (ICP): >90% have >180 mmH2O → leads to obtundation, coma, papilledema, and Cushing reflex. • Seizures: Occur in 15–40% of patients due to ischemia, venous thrombosis, or hyponatremia.
4.1 Specific Clinical Clues¶
• Meningococcemia: Petechial rash on trunk/extremities, mucosa, palms/soles; biopsy reveals organisms on Gram's stain. • RMSF: Petechial rash progressing to purpuric/necrotic lesions; rash begins at wrists/ankles. • Ehrlichiosis: Fever, confusion, rash (20%), leukopenia/thrombocytopenia.
5. DIFFERENTIAL DIAGNOSIS¶
• Viral Meningitis/Encephalitis: → HSV encephalitis: Lymphocytic pleocytosis, normal glucose; MRI shows temporal lobe lesions. → Other viruses (Table 143-4): Enteroviruses, VZV, EBV, Arboviruses (WNV), HIV. • Infectious Mimics: RMSF/Ehrlichiosis (petechial rash); focal suppurative infections (subdural/epidural empyema, brain abscess). • Noninfectious Mimics: SAH, medication-induced hypersensitivity, carcinomatous meningitis, sarcoidosis, Behçet's syndrome.
6. INVESTIGATIONS & DIAGNOSIS¶
- Initial Actions: Obtain blood cultures and initiate empirical antibiotics/dexamethasone within 60 min of arrival.
- Lumbar Puncture (LP): Safe in immunocompetent patients without focal deficits or papilledema.
- CSF Analysis (Table 143-2): → Opening pressure: >180 mmH2O. → White blood cells: 10/μL to 10,000/μL; neutrophils predominate. → Red blood cells: Absent in nontraumatic tap. → Glucose: <2.2 mmol/L (<40 mg/dL). → CSF/serum glucose ratio: <0.4 (highly suggestive of bacterial meningitis). → Protein: >0.45 g/L (>45 mg/dL). → Gram's stain: Positive in >60%. → Culture: Positive in >80%. → PCR: Detects DNA for S. pneumoniae, N. meningitidis, E. coli, L. monocytogenes, H. influenzae, GBS.
- Imaging: MRI preferred over CT for detecting cerebral edema/ischemia; meningeal enhancement is non-specific.
Table 143-2 Cerebrospinal Fluid (CSF) Abnormalities in Bacterial Meningitis
| Parameter | Finding |
|---|---|
| Opening pressure | >180 mmH2O |
| White blood cells | 10/μL to 10,000/μL; neutrophils predominate |
| Red blood cells | Absent in nontraumatic tap |
| Glucose | <2.2 mmol/L (<40 mg/dL) |
| CSF/serum glucose | <0.4 |
| Protein | >0.45 g/L (>45 mg/dL) |
| Gram's stain | Positive in >60% |
| Culture | Positive in >80% |
| PCR | Detects bacterial DNA |
7. THERAPEUTIC APPROACH¶
- Immediate Intervention: Initiate antibiotics and dexamethasone within 60 min of ER arrival.
- Dexamethasone: 10 mg IV q6h; administered 20 min before or with first antibiotic dose.
- Empirical Therapy (Table 143-1): → Preterm infants to infants <1 month: Ampicillin + cefotaxime. → Infants 1–3 months: Ampicillin + cefotaxime or ceftriaxone. → Immunocompetent children >3 months and adults <55: Cefotaxime, ceftriaxone, or cefepime + vancomycin. → Adults >55 and adults of any age with alcoholism or other debilitating illnesses: Ampicillin + ceftriaxome, ceftriaxone, or cefepime + vancomycin. → Hospital-acquired, posttraumatic/postneurosurgery, neutropenic, or impaired cell-mediated immunity: Ampicillin + ceftazidime or meropenem + vancomycin.
- Specific Antimicrobial Therapy (Table 143-3): → N. meningitides: ◦ Penicillin-sensitive: Penicillin G or ampicillin. ◦ Penicillin-resistant: Ceftriaxone or ceftriaxome. → S. pneumoniae: ◦ Penicillin-sensitive: Penicillin G. ◦ Penicillin-intermediate: Ceftriaxone/cefot1axime/cefepime. ◦ Penicillin-resistant: Ceftriaxone + vancomycin. → Gram-negative bacilli (except Pseudomonas spp.): Ceftriaxone or cefot1axime. → Pseudomonas aeruginosa: Ceftazidime, cefepime, or meropenem. → Staphylococci spp.: ◦ Methicillin-sensitive: Nafcillin. ◦ Methicillin-resistant: Vancomycin. → L. monocytogenes: Ampicillin + gentamicin. → H. influenzae: ◦ β-lactamase positive: Ceftriaxone/cefot1axime. ◦ β-lactamase negative: ampicillin. → S. agalactiae: Penicillin G or ampicillin. → B. fragilis: Metronidazole. → Fusobacterium spp.: Metronidazole.
- Adjunctive Therapy: Add acyclovir for suspected HSV encephalitis.
Table 143-1 Antibiotics Used in Empirical Therapy of Bacterial Meningitis and Focal Central Nervous System Infections
| INDICATION | ANTIBIOTIC |
|---|---|
| Preterm infants to infants <1 month | Ampicillin + cefotaxime |
| Infants 1–3 months | Ampicillin + ceftriaxone or ceftriaxome |
| Immunocompetent children >3 months and adults <55 | Cefotaxime, ceftriaxone, or cefepime + vancomycin |
| Adults >55 and adults of any age with alcoholism or other debilitating illnesses | Ampicillin + ceftriaxome, ceftriaxone, or cefepime + vancomycin |
| Hospital-acquired meningitis, posttraumatic or postneurosurgery meningitis, neutropenic patients, or patients with impaired cell-mediated immunity | Ampicillin + ceftazidime or meropenem + vancomycin |
Table 143-3 Antimicrobial Therapy of Central Nervous System Bacterial Infections Based on Pathogen
| ORGANISM | ANTIBIOTIC |
|---|---|
| Neisseria meningitides | Penicillin-sensitive: Penicillin G or ampicillin; Penicillin-resistant: Ceftriaxone or ceftriaxome |
| Streptococcus pneumoniae | Penicillin-sensitive: Penicillin G; Penicillin-intermediate: Ceftriaxone/cefot1axime/cefepime; Penicillin-resistant: Ceftriaxone + vancomycin |
| Gram-negative bacilli (except Pseudomonas spp.) | Ceftriaxone or ceftriaxome |
| Pseudomonas aeruginosa | Ceftazidime, cefepime, or meropenem |
| Staphylococci spp. | Methicillin-sensitive: Nafcillin; Methicillin-resistant: Vancomycin |
| Listeria monocytogenes | Ampicillin + gentamicin |
| Haemophilus influenzae | Ceftriaxone/cefot1axime (β-lactamase positive); ampicillin (β-lactamase negative) |
| Streptococcus agalactiae | Penicillin G or ampicillin |
| Bacteroides fragilis | Metronidazole |
| Fusobacterium spp. | Metronidazole |
7.2 Pneumococcal Meningitis¶
• Mortality: ~20% despite antibiotics. • Risk factors: pneumococcal pneumonia, alcoholism, diabetes, splenectomy. • CSF findings: PMN >100 cells/μL, glucose <2.2 mmol/L.
7.3 Listeria Meningitis¶
• Target population: neonates, pregnant women, and adults >50 years. • Treatment: Ampicillin + gentamicin. • Mortality: ~15%.
7.4 Staphylococcal Meningitis¶
• Context: Common after neurosurgical procedures or subcutaneous Ommaya reservoirs. • Treatment: Nafcillin (methicillin-sensitive); vancomycin (methicillin-resistant).
7.5 Gram-Negative Bacillary Meningitis¶
• Context: Common in chronic diseases (diabetes, cirrhosis). • Empirical therapy: ceftriaxone/cefot1axime. • Pseudomonas aeruginosa: ceftazidime/cefepime/meropenem.
8. PROGNOSIS & COMPLICATIONS¶
• Mortality Rates: → 3–7% for H. influenzae, N. meningitidis, or GBS. → 20% for S. pneumoniae. → 15% for L. monocytogenes. • Clinical Complications: Seizures (15–40%), hydrocephalus, cerebral edema, vasculitis, thrombosis, herniation. • Long-term Sequelae: Hearing loss, cognitive deficits, or motor impairments.
9. SPECIAL CONSIDERATIONS¶
• Vaccination: → Quadrivalent (A, C, W-135, Y) and serogroup B meningococcal vaccines reduce incidence. → Pentavalent vaccine required for patients with complement deficiencies. • Neonatal/Pregnant Patients: Require ampicillin for L. monocytogenes. • Meningococcal Contacts: Chemoprophylaxis with rifampin, azithromycin, or ceftriaxone.
10. KEY PEARLS & CLINICAL TRAPS¶
• Pearls: → Dexamethasone reduces mortality and hearing loss. → CSF/serum glucose ratio <0.4 is highly suggestive of bacterial meningitis. • Traps: → Kernig's/Brudzinski's signs may be absent in young or elderly patients. → CSF glucose may normalize after dextrose administration if LP is delayed.
Reference Tables¶
TABLE 143-1 Antibiotics Used in Empirical Therapy of Bacterial Meningitis and Focal Central Nervous System Infections a…¶
Harrison's 22e, p.1121
| INDICATION | ANTIBIOTIC | |
|---|---|---|
| Preterm infants to infants <1 month |
Ampicillin + cefotaxime | |
| Immunocompetent children >3 months and adults <55 |
Cefotaxime, ceftriaxone, or cefepime + vancomycin | |
| Hospital-acquired meningitis, posttraumatic or postneurosurgery meningitis, neutropenic patients, or patients with impaired cell-mediated immunity |
Ampicillin + ceftazidime or meropenem + vancomycin | |
| ANTIMICROBIAL AGENT | TOTAL DAILY DOSE AND DOSING INTERVAL | |
| CHILD (>1 MONTH) | ADULT | |
| Ampicillin | 300 (mg/kg)/d, q6h | 12 g/d, q4h |
| 150 (mg/kg)/d, q8h | ||
| Cefotaxime | 225–300 (mg/kg)/d, q6h | 12 g/d, q4h |
| 100 (mg/kg)/d, q12h | ||
| Ceftazidime | 150 (mg/kg)/d, q8h | 6 g/d, q8h |
| 7.5 (mg/kg)/d, q8hb | ||
| Meropenem | 120 (mg/kg)/d, q8h | 6 g/d, q8h |
| 30 (mg/kg)/d, q6h | ||
| Nafcillin | 200 (mg/kg)/d, q6h | 12 g/d, q4h |
| 400,000 (U/kg)/d, q4h | ||
| Vancomycin | 45–60 (mg/kg)/d, q6h | 45–60 (mg/kg)d, q6–12hb |
TABLE 143-2 Cerebrospinal Fluid (CSF) Abnormalities in Bacterial Meningitis Opening pressure White blood cells Red…¶
Harrison's 22e, p.1121
| Opening pressure | >180 mmHO 2 |
|---|---|
| Red blood cells | Absent in nontraumatic tap |
| CSF/serum glucose | <0.4 |
| Gram’s stain | Positive in >60% |
| PCR | Detects bacterial DNA |
TABLE 143-3 Antimicrobial Therapy of Central Nervous System Bacterial Infections Based on Pathogen a ORGANISM Neisseria…¶
Harrison's 22e, p.1122
| ORGANISM | ANTIBIOTIC |
|---|---|
| Neisseria meningitides | |
| Penicillin-sensitive | Penicillin G or ampicillin |
| Penicillin-resistant | Ceftriaxone or cefotaxime |
| Gram-negative bacilli (except Pseudomonas spp.) |
Ceftriaxone or cefotaxime |
| Staphylococci spp. | |
| Methicillin-sensitive | Nafcillin |
| Methicillin-resistant | Vancomycin |
| Haemophilus influenzae | Ceftriaxone or cefotaxime if β-lactamase positive; ampicillin if β-lactamase negative |
| Bacteroides fragilis | Metronidazole |
TABLE 143-4 Viruses Causing Acute Meningitis in North America COMMON Enteroviruses (coxsackieviruses, echoviruses, and…¶
Harrison's 22e, p.1124
| COMMON | LESS COMMON |
|---|---|
| Enteroviruses (coxsackieviruses, echoviruses, and the numbered enteroviruses) Varicella-zoster virus Herpes simplex virus 2 Epstein-Barr virus Arthropod-borne viruses (notably WNV) HIV |
Herpes simplex virus 1 Human herpesvirus 6 Cytomegalovirus Lymphocytic choriomeningitis virus Mumps Zika and other non-WNV arboviruses |