20.2 Bacterial Meningitis, CSF Interpretation & Toxic Shock Syndrome

3. Acute Bacterial Meningitis: Pathogens, Presentation & Emergency Management

Acute bacterial meningitis is a medical emergency with high mortality ($15\text{–}25%$) and substantial risk of long-term neurological sequelae (sensorineural hearing loss, focal cognitive deficits, epilepsy). Rapid parenchymal and meningeal inflammation results from subarachnoid bacterial replication following haematogenous seeding or direct contiguous spread (e.g., otitis media, mastoiditis, sinus fracture).

Causative Pathogens Stratified by Host Age and Risk

• Immunocompetent Adults (Ages 18–60):
  • Streptococcus pneumoniae (Pneumococcus): The most common causative pathogen overall in adults ($> 50%$ of cases). Associated with severe disease, impaired consciousness, focal neurological deficits, and high mortality. Predisposing factors include asplenia, otitis media, pneumonia, head injury with basilar skull fracture and CSF leak, and alcohol excess.
  • Neisseria meningitidis (Meningococcus): Predominates in adolescents and young adults (ages 15–24, university halls, military barracks). Serogroups B, C, W, and Y are principal culprits in the UK. Characterized by rapid progression and petechial or non-blanching purpuric skin rash.
• Neonates ($< 3\text{ months}$): Streptococcus agalactiae (Group B Streptococcus), Escherichia coli (K1 capsular strain), and Listeria monocytogenes.
• Elderly Adults ($> 60\text{ years}$) & Immunocompromised Hosts:
  • Listeria monocytogenes: A facultative intracellular Gram-positive bacillus acquired via ingestion of unpasteurized dairy, soft cheeses, or deli meats. Causes severe rhombencephalitis (brainstem encephalitis), ataxia, and cranial neuropathies. Predominantly strikes individuals aged $> 60$, pregnant women, and patients with impaired cell-mediated immunity (haematological malignancy, chemotherapy, biologic agents, corticosteroid therapy, cirrhosis, and alcohol misuse).

Clinical Presentation

• The Classic Triad: Fever, altered mental state (GCS $< 15$), and neck stiffness (meningism). All three features are present in only $45%$ of patients, but $> 95%$ possess at least two signs from headache, fever, neck stiffness, and altered consciousness.
• Physical Signs of Meningeal Irritation:
  • Kernig's Sign: Inability to extend the knee beyond $135^\circ$ when the hip is flexed at $90^\circ$ due to severe pain and hamstring spasm.
  • Brudzinski's Sign: Involuntary flexion of the hips and knees upon passive flexion of the patient's neck.
• Cutaneous Hallmarks: Non-blanching petechial or purpuric rash is pathognomonic of meningococcal septicaemia (N. meningitidis), although widespread purpura fulminans can rarely complicate overwhelming pneumococcal sepsis in asplenic patients.

Emergency Management Protocol (BIA & NICE Guidelines)

1. Immediate Parenteral Antibiotic Administration: Antibiotics must never be delayed for neuroimaging or lumbar puncture. If bacterial meningitis is suspected in primary care, immediate intramuscular or intravenous benzylpenicillin (or ceftriaxone) should be administered prior to urgent hospital transfer.
2. Hospital Empirical Antimicrobial Regimen:
   • Adults aged 18–60 years: Intravenous ceftriaxone $2\text{ g}$ 12-hourly (or cefotaxime $2\text{ g}$ 6-hourly). High-dose third-generation cephalosporins achieve bactericidal subarachnoid concentrations against penicillin-resistant pneumococci and meningococci.
   • Adults aged $> 60$ years OR immunocompromised OR pregnant: Add intravenous ampicillin or amoxicillin $2\text{ g}$ 4-hourly to provide dedicated coverage against Listeria monocytogenes (which is intrinsically resistant to all cephalosporins).
   • Severe Penicillin/Beta-lactam Anaphylaxis: IV chloramphenicol ($25\text{ mg/kg}$ 6-hourly) plus IV vancomycin, plus co-trimoxazole if Listeria coverage is required.
3. Adjunctive Corticosteroid Therapy (Dexamethasone):
   • Regimen: Intravenous dexamethasone $10\text{ mg}$ 6-hourly (or $0.15\text{ mg/kg}$ QDS).
   • Timing: Must be administered prior to or concurrently with the first dose of antimicrobial therapy (up to a maximum of 4 hours after antibiotics; ineffective if given $> 12$ hours later).
   • Evidence & Duration: The European Dexamethasone in Adulthood Bacterial Meningitis trial demonstrated that adjunctive dexamethasone significantly reduces unfavourable outcomes (relative risk 0.59) and mortality in Streptococcus pneumoniae meningitis, and significantly reduces sensorineural deafness in meningococcal disease. Continue for 4 days if S. pneumoniae is confirmed; discontinue immediately if Listeria or non-bacterial aetiologies are identified.

Indications for Cranial CT Scan Prior to Lumbar Puncture

Performing a lumbar puncture in the presence of an intracranial space-occupying lesion or acute brain swelling risks fatal transtentorial or cerebellar tonsillar herniation (coning). CT brain is mandatory before LP if any of the following 'red flag' criteria are present:

1. Focal neurological deficits (e.g., hemiparesis, visual field defect, unequal pupils, facial asymmetry)
2. New-onset or recent seizures (within preceding 1 week)
3. Significant encephalopathy or depressed consciousness (GCS $< 12$ or a rapid fall in GCS $\ge 2$ points)
4. Papilloedema on fundoscopy (indicates established raised intracranial pressure)
5. Severe immunocompromised state (known HIV/AIDS, immunosuppressive therapy, active organ transplant)

Note: If CT is indicated, obtain blood cultures, immediately administer IV dexamethasone and empirical antibiotics, and arrange CT imaging without delaying therapeutic intervention.

Chemoprophylaxis for Close Contacts

Close household contacts, dormitory room-mates, and kissing contacts of confirmed meningococcal disease (N. meningitidis) within the 7 days prior to onset require urgent chemoprophylaxis to eradicate nasopharyngeal carriage:

• First-line UKHSA/NICE Regimen: A single oral dose of ciprofloxacin $500\text{ mg}$ (safe across all ages and during pregnancy under UKHSA guidance).
• Alternative Regimen: Oral rifampicin $600\text{ mg}$ 12-hourly for 2 days (renders oral contraceptives ineffective; stains urine/soft contact lenses red-orange).
• Pregnancy Alternative: Intramuscular ceftriaxone $250\text{ mg}$ stat.
• Note: Close contacts of pneumococcal or Listeria meningitis do not require chemoprophylaxis.

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4. Cerebrospinal Fluid (CSF) Analysis in CNS Infections

Interpretation of lumbar puncture parameters is a recurring cornerstone of MRCP(UK) Part 1 examinations.

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5. Toxic Shock Syndrome (TSS): Staphylococcal vs. Streptococcal

Toxic shock syndrome is an acute, life-threatening toxin-mediated multisystem illness characterized by rapid onset of fever, hypotension, generalized erythroderma, and progressive multiorgan failure.

Molecular Pathophysiology: The Superantigen Mechanism

Conventional peptide antigens require internalisation, lysosomal processing by antigen-presenting cells (APCs), and presentation within the peptide-binding groove of Major Histocompatibility Complex (MHC) Class II molecules to activate specific T-cell receptor (TCR) clones ($< 0.01%$ of total T-cell pool).

In contrast, bacterial superantigens circumvent normal processing. They bind directly and simultaneously to the external invariant surface of MHC Class II molecules on APCs and specific Variable beta ($V_\beta$) regions of T-cell receptors. This bypasses antigen specificity and triggers massive, uncontrolled polyclonal T-cell activation ($5\text{–}20%$ of all systemic T-lymphocytes). The ensuing hypercytokinaemia (interferon-gamma, IL-1, IL-2, IL-6, TNF-$\alpha$, and TNF-$\beta$) induces diffuse capillary leak, distributive vasoplegia, and multiorgan destruction.

Staphylococcal vs. Streptococcal Toxic Shock Syndrome

Diagnostic Hallmarks & Multiorgan Criteria (CDC/UK Standards)

1. Fever: Temperature $\ge 38.9^\circ\text{C}$ ($102^\circ\text{F}$)
2. Hypotension: Systolic blood pressure $\le 90\text{ mmHg}$ or orthostatic syncope
3. Diffuse Rash: Generalized macular erythroderma resembling a severe sunburn
4. Desquamation: Fine lamellar desquamation occurring characteristically 1 to 2 weeks following disease onset, particularly involving the palms of the hands and soles of the feet
5. Multisystem Involvement ($\ge 3$ organ systems):
   • Gastrointestinal: Profuse vomiting or watery diarrhoea at onset
   • Muscular: Severe myalgia or serum creatine kinase (CK) elevated $\ge 2\times$ upper limit of normal
   • Mucous membranes: Intense erythema of vaginal, oropharyngeal, or conjunctival mucosa without purulence
   • Renal: Serum creatinine $\ge 2\times$ upper limit of normal or pyuria ($> 5$ WBCs/HPF) without infection
   • Hepatic: Total bilirubin, ALT, or AST $\ge 2\times$ upper limit of normal
   • Haematological: Severe thrombocytopenia ($< 100 \times 10^9\text{/L}$)
   • Central Nervous System: Disorientation, delirium, or altered consciousness without focal signs

Therapeutic Management

• Antitoxin Pharmacotherapy: Intravenous clindamycin ($600\text{–}900\text{ mg}$ 6- to 8-hourly) is mandatory. As a lincosamide that binds the 50S ribosomal subunit, clindamycin directly inhibits bacterial protein synthesis, halting the transcription and transcription-independent release of superantigen exotoxins (TSST-1, SpeA). This action is unaffected by the 'Eagle effect' (reduced penicillin efficacy in high bacterial inocula during stationary growth phase).
• Bactericidal Backbone: Combine clindamycin with high-dose intravenous flucloxacillin (or vancomycin if methicillin-resistant S. aureus [MRSA] is suspected) for Staphylococcal TSS, or intravenous benzylpenicillin (or ceftriaxone) for Streptococcal TSS.
• Intravenous Immunoglobulin (IVIG): High-dose IVIG ($1\text{–}2\text{ g/kg}$) contains high titres of neutralizing antibodies against superantigen exotoxins. Recommended in severe, refractory streptococcal TSS or necrotizing fasciitis.
• Surgical Source Control: Immediate removal of retained foreign bodies (tampons, nasal tampons, surgical packs) and urgent radical surgical debridement of necrotic soft tissue in suspected necrotizing fasciitis.