What is the best course of treatment for a patient with fever causing altered mental status, considering age and underlying medical conditions such as dementia, immunosuppression, or other comorbidities?

Fever Causing Altered Mental Status: Treatment Approach

Immediately initiate empiric antibiotic therapy with ceftriaxone 2g IV every 12 hours after obtaining blood cultures, as bacterial meningitis must be presumed and treated urgently in any patient presenting with fever and altered mental status—mortality remains high without prompt treatment. 1, 2, 3

Immediate Actions (Do Not Delay Antibiotics)

• Start empiric antibiotics immediately after obtaining 2 sets of blood cultures, even before imaging or lumbar puncture 1, 3
• Administer ceftriaxone 2g IV every 12 hours; add vancomycin 15-20 mg/kg IV every 8-12 hours if pneumococcal resistance is a concern in your region 1
• Consider IV acyclovir 10 mg/kg every 8 hours until HSV PCR results return negative, as encephalitis remains in the differential 1
• Never delay antibiotics while awaiting CT or LP—this is a critical pitfall that increases mortality 1, 2, 3

Diagnostic Evaluation

Clinical Assessment

• Do not rely on the absence of neck stiffness to rule out meningitis—the classic triad of fever, neck stiffness, and altered mental status is present in only 41-51% of bacterial meningitis cases 1, 2
• Neck stiffness has only 31% sensitivity in adults; Kernig and Brudzinski signs are similarly unreliable 1
• Assess for encephalitis using the International Encephalitis Consortium criteria: altered mental status lasting ≥24 hours is the major criterion, with fever ≥38°C within 72 hours being one of six minor criteria (need ≥2 minor criteria for possible encephalitis) 4

Laboratory Testing

• Obtain ESR and CRP—elevated in >90% of bacterial meningitis and vertebral osteomyelitis cases 1
• Measure serum creatinine to assess renal function, particularly important if considering acyclovir (can cause neurotoxicity in renal impairment) 5

Imaging Before Lumbar Puncture

Perform non-contrast head CT only if any of these are present before LP 1, 3:

• Focal neurologic deficits
• Immunocompromised state (HIV/AIDS, immunosuppressive therapy)
• History of CNS disease (mass lesion, stroke, focal infection)
• New-onset seizure within 1 week
• Papilledema
• Altered consciousness (GCS <11)

If none of these contraindications exist, proceed directly to LP without imaging 3

Lumbar Puncture

• Collect at least 22 mL of CSF for comprehensive testing 3
• Send for: cell count with differential, glucose, protein, Gram stain, bacterial culture, and HSV PCR 1, 3
• Normal opening pressure, <5 WBC/μL, and normal protein essentially exclude meningitis in immunocompetent patients 3
• CSF PCR has 87-100% sensitivity and 98-100% specificity, especially valuable if antibiotics were given before LP 3

Special Population Considerations

Elderly Patients with Dementia

• Metabolic encephalopathy (delirium) is the most common cause of altered mental status with fever in this population 6
• Age and pre-existing dementia are independent predictors of altered mental status in febrile illness 6
• However, never assume delirium without excluding meningitis—perform LP unless contraindicated 1, 3
• Goals of care discussions are appropriate given advanced dementia prognosis, but acute bacterial meningitis still requires treatment if identified 7

Immunosuppressed Patients

• Lower threshold for CT before LP due to higher risk of CNS mass lesions 1
• Consider fungal and tuberculous meningitis in addition to bacterial causes 1
• Note that immunosuppressed patients may not mount a fever despite active CNS infection 4
• CSF may lack pleocytosis in immunocompromised hosts, but this does not exclude meningitis 4

Patients on Antipsychotic Medications

• Consider neuroleptic malignant syndrome (NMS) if patient is taking dopamine antagonists 4
• NMS presents with fever, altered mental status, muscle rigidity, and autonomic instability 4
• Mortality has decreased from 76% to <15% with recognition and treatment 4
• This is a distinct entity requiring different management (discontinue antipsychotic, supportive care, consider dantrolene or bromocriptine) 4

Patients on Hemodialysis

• If catheter-related bloodstream infection (CRBSI) is suspected, altered mental status is one of the symptoms prompting immediate evaluation 4
• Remove infected catheter for CRBSI due to S. aureus, Pseudomonas, or Candida species 4
• However, still evaluate for meningitis if altered mental status is prominent, as bacteremia can seed the CNS 4

Common Pitfalls to Avoid

• Never assume metabolic encephalopathy without excluding meningitis—even though metabolic causes are common (92.8% in one COVID-19 cohort), bacterial meningitis is fatal if untreated 6, 1
• Never wait for imaging results to start antibiotics if meningitis is suspected 1, 2, 3
• Never rely on absence of fever or meningeal signs to rule out CNS infection—sensitivity is poor 1, 2
• Never perform LP in patients with focal deficits, altered consciousness, or signs of increased intracranial pressure without CT first 1, 3
• Never assume all altered mental status in ICU patients is delirium—approximately 25% of neurocritical patients develop fever, with nearly half being non-infectious, but CNS infection must still be excluded 3

Ongoing Management

• Continue empiric antibiotics until culture results and sensitivities return 1, 2
• If bacterial meningitis is confirmed, duration is typically 10-14 days for most organisms (longer for certain pathogens) 1
• For tuberculous meningitis, treat with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, then isoniazid and rifampin for 7-10 additional months 4
• Consider adjunctive corticosteroids for tuberculous meningitis, particularly in lethargic patients (Stage II disease), though evidence with rifampin-based regimens is limited 4