What is the management of meningoencephalitis?

Management of Meningoencephalitis

Initiate empirical antimicrobial therapy immediately upon clinical suspicion—specifically intravenous acyclovir for viral encephalitis plus vancomycin and ceftriaxone (or cefotaxime) for bacterial meningitis—without waiting for diagnostic confirmation, as delayed treatment significantly increases mortality and neurologic disability. 1, 2, 3

Immediate Empirical Antimicrobial Therapy

Start Treatment Before Diagnostic Confirmation

• Administer antimicrobials as soon as meningoencephalitis is suspected, even before lumbar puncture or neuroimaging if these procedures will cause delay 1, 2
• Blood cultures should be obtained immediately, but do not delay antibiotics while awaiting results 2
• Early antimicrobial administration (particularly third-generation cephalosporins and acyclovir at ICU admission) is independently protective against poor functional outcomes 3

Empirical Regimen Components

• Acyclovir: Administer intravenously at appropriate dosages immediately for all suspected encephalitis cases to cover HSV encephalitis, which is the most common cause and cannot be missed 1, 4, 5
• Vancomycin plus ceftriaxone or cefotaxime: Use this combination for suspected bacterial meningitis in infants, children, and adults to cover resistant Streptococcus pneumoniae and other common pathogens 1
• Add coverage for rickettsial or ehrlichial infection if epidemiologically appropriate 1

Dosing Specifics

• Adults: Ceftriaxone 1-2 grams IV once or twice daily (maximum 4 grams/day) 6
• Pediatric meningitis: Ceftriaxone 100 mg/kg IV initially (not exceeding 4 grams), then 100 mg/kg/day (maximum 4 grams daily) given once daily or divided every 12 hours 6
• Neonates: Administer IV doses over 60 minutes (not 30 minutes) to reduce bilirubin encephalopathy risk 6

Diagnostic Lumbar Puncture Timing

When to Perform Immediately

• Perform lumbar puncture immediately to measure opening pressure and obtain CSF for analysis in patients without contraindications 2
• Measure opening pressure at baseline—this is critical as elevated intracranial pressure (ICP ≥25 cm CSF) occurs in approximately 50% of patients and correlates with early mortality 2

When to Delay for Neuroimaging First

• Obtain CT or MRI before lumbar puncture only if focal neurologic signs, severely impaired mentation (GCS ≤10), or papilledema are present, as these indicate mass lesions or obstructive hydrocephalus that increase herniation risk 1, 2
• Do not delay antimicrobials while awaiting imaging—treat first, then image 1, 2

Management of Elevated Intracranial Pressure

Initial ICP Assessment and Intervention

• If opening pressure is ≥25 cm CSF with symptoms of increased ICP, perform therapeutic lumbar puncture to reduce pressure by 50% if extremely high, or to normal pressure of ≤20 cm CSF 2
• Failure to measure and manage elevated CSF pressure results in new neurologic abnormalities in 50% of patients versus only 8% when guidelines are followed 2
• Patients who died within the first 2 weeks had baseline ICP ≥25 cm CSF in 11 of 12 cases 2

Ongoing ICP Management

• For persistent pressure elevation ≥25 cm CSF with symptoms, repeat lumbar puncture daily until CSF pressure and symptoms stabilize for >2 consecutive days 2
• Consider temporary percutaneous lumbar drains for patients requiring repeated daily lumbar punctures—these can be safely maintained for up to 13 days with bacterial superinfection risk <5% 2
• Ventriculostomy should be considered for obstructive hydrocephalus or when lumbar puncture is contraindicated 2
• Permanent ventriculoperitoneal shunts should only be placed after appropriate antifungal therapy has been initiated and more conservative measures have failed 2

Critical Medications to AVOID

• Do NOT use acetazolamide—a randomized trial was stopped prematurely due to severe metabolic acidosis and complications 2
• Do NOT use high-dose corticosteroids for ICP elevation—mortality and clinical deterioration were observed more commonly in corticosteroid recipients 2

Adjunctive Dexamethasone for Bacterial Meningitis

When to Administer

• Give adjunctive dexamethasone to children and adults with suspected bacterial meningitis before or at the time of initiating antibiotics 1, 7
• The rationale is that subarachnoid space inflammatory response is a major contributor to morbidity and mortality, and attenuation decreases cerebral edema, increased intracranial pressure, altered cerebral blood flow, and neuronal injury 1

Pediatric Evidence

• In children, dexamethasone (0.15 mg/kg every 6 hours for 2-4 days) has confirmed benefit for H. influenzae type b meningitis and suggested benefit for pneumococcal meningitis when commenced with or before antimicrobial therapy 1
• Greatest clinical benefit is for hearing outcomes, with reduced hearing impairment overall in H. influenzae meningitis (combined OR 0.31) 1

Supportive Critical Care Management

Hemodynamic Support

• Maintain euvolemia with crystalloids as initial fluid of choice to achieve normal hemodynamic parameters and mean arterial pressure ≥65 mmHg 2
• Use norepinephrine as the initial vasopressor for hypotension after euvolemia is restored 2
• Cardiovascular failure at ICU admission is independently associated with poor functional outcome (OR 1.72) 3

Seizure Management

• Treat suspected or proven seizures early—seizures occur in 15% of bacterial meningitis patients and are associated with worse outcomes 2
• Patients with suspected status epilepticus (including non-convulsive status) with fluctuating GCS off sedation or subtle abnormal movements require EEG monitoring 2

Respiratory Support

• Respiratory failure at ICU admission is independently associated with poor functional outcome (OR 1.76) 3
• Monitor closely for respiratory complications as they are actionable factors for which improvement can be made 3

Etiology-Specific Therapy

Cryptococcal Meningoencephalitis

• Primary induction therapy: Amphotericin B deoxycholate (0.7-1.0 mg/kg/day IV) plus flucytosine (100 mg/kg/day orally in 4 divided doses) for at least 2 weeks 1, 2
• Alternative for renal dysfunction: Liposomal amphotericin B (3-4 mg/kg per day) in patients with initial or developing renal dysfunction or receiving other nephrotoxic agents 1
• Consolidation therapy: Fluconazole (400 mg daily) for minimum 8 weeks after successful induction 2
• The 2-week CSF culture result is critical—negative cultures should be the goal, and patients not achieving this need prolonged induction therapy 2

ADEM (Acute Disseminated Encephalomyelitis)

• First-line therapy: High-dose intravenous methylprednisolone (1 g IV daily for at least 3-5 days, or 20-30 mg/kg/day with maximum 1 g/day) 1, 4
• Follow with oral corticosteroid taper over 4-6 weeks—steroid tapers shorter than 4-6 weeks lead to symptom recurrence and must be avoided 4
• Second-line therapy: Consider plasma exchange or IVIG (2 g/kg over 2-5 days) if no meaningful clinical or radiological improvement after 3-5 days of corticosteroids 1, 4
• Plasma exchange should be considered in patients who respond poorly to corticosteroids 1

Targeted Therapy After Pathogen Identification

• Once an etiologic agent is identified, antimicrobial therapy should be targeted to that infectious agent, or discontinued if treatment directed against the etiologic agent is not available 1
• Targeted therapy is based on presumptive pathogen identification by CSF Gram stain, with the assumption that antimicrobial resistance is likely for initial therapy 1

Duration of Therapy

General Principles

• Continue therapy for at least 2 days after signs and symptoms of infection have disappeared 6
• Usual duration is 4-14 days; in complicated infections, longer therapy may be required 6
• For meningitis, usual duration is 7-14 days 6
• When treating infections caused by Streptococcus pyogenes, continue therapy for at least 10 days 6

Prognostic Factors and Risk Stratification

Variables Associated with Poor Functional Outcome

• Age >60 years (OR 1.75) 3
• Immunodepression (OR 1.98) 3
• Time between hospital and ICU admission >1 day (OR 2.02) 3
• Motor component on GCS ≤3 (OR 2.23) 3
• Hemiparesis/hemiplegia (OR 2.48) 3
• Respiratory failure (OR 1.76) 3
• Cardiovascular failure (OR 1.72) 3

Overall Outcomes

• Meningoencephalitis requiring ICU admission is associated with 50.5% poor functional outcome at 3 months, including 25.8% mortality 3
• Mortality rates range from 11-25% with functional disability in 15-25% of survivors 8

Critical Pitfalls to Avoid

• Never delay empirical acyclovir while awaiting diagnostic confirmation, as HSV encephalitis cannot be missed and requires immediate antiviral therapy 4
• Never taper steroids faster than 4-6 weeks in ADEM, as premature discontinuation causes relapse 4
• Never use acetazolamide for elevated ICP management due to severe metabolic acidosis risk 2
• Never use high-dose corticosteroids for elevated ICP in fungal meningitis due to increased mortality 2
• Never delay antimicrobials for lumbar puncture or imaging—treat first, then diagnose 1, 2