What is the appropriate management for a patient presenting with lethargy, disorientation, high fever, leukopenia, and elevated CRP?

Management of Febrile Patient with Altered Mental Status and Elevated CRP

This patient requires immediate empiric broad-spectrum antibiotics for presumed severe bacterial infection or sepsis, with urgent evaluation for central nervous system infection given the altered mental status.

Immediate Assessment and Stabilization

Critical Recognition

• Lethargy and disorientation with high fever constitute a medical emergency requiring immediate intervention 1
• The WBC of 5.23 × 10⁹/L is borderline low-normal, while CRP of 23 mg/L indicates significant bacterial infection 2, 3
• Altered mental status with fever mandates consideration of meningitis or encephalitis until proven otherwise 1

Urgent Diagnostic Workup

• Lumbar puncture is mandatory when altered mental status accompanies fever 1
• Obtain blood cultures, complete blood count with differential, comprehensive metabolic panel, and chest imaging before antibiotics but do not delay treatment 1, 4
• The elevated CRP (23 mg/L) suggests bacterial infection, though this level can occur in viral infections during days 2-4 of illness 5

Empiric Antibiotic Therapy

Immediate Treatment Regimen

• Start ceftazidime plus ampicillin (to cover Listeria monocytogenes) OR meropenem immediately for presumed bacterial meningitis 1
• If meningitis is excluded but severe infection persists, use cefepime 2g IV every 8 hours as empiric therapy for severe bacterial infection 6
• Add aciclovir at high doses empirically for possible viral encephalitis while awaiting diagnostic results 1

Rationale for Aggressive Coverage

• The combination of altered mental status and fever requires coverage for both bacterial meningitis (including Listeria) and viral encephalitis 1
• CRP of 23 mg/L, while not extremely elevated, indicates significant inflammation requiring treatment 2, 3
• Normal-range WBC does not exclude serious bacterial infection; 3.8% of febrile ED patients with normal WBC and elevated CRP have bacterial infections requiring admission 7

Risk Stratification and Monitoring

High-Risk Features Present

• Altered mental status (lethargy, disorientation) places this patient in the high-risk category requiring intensive monitoring every 2-4 hours 1
• Hemodynamic instability assessment is critical; unstable patients require urgent infectious disease consultation 1, 4

Serial Monitoring Requirements

• Assess clinical status, fever trends, and mental status every 2-4 hours initially 1
• Repeat CRP at 48 hours; failure to decrease suggests treatment failure or inadequate coverage 2
• Daily assessment of renal function is indicated while on antibiotics 1

48-Hour Reassessment Algorithm

If Patient Improves

• Continue antibiotics if pathogen identified, tailoring to susceptibilities 1
• If no pathogen found but clinically stable and afebrile, continue current regimen 1

If Patient Deteriorates or Remains Febrile

• Broaden antibacterial coverage or rotate regimen; consider adding glycopeptide 1
• Seek urgent infectious disease or clinical microbiologist consultation 1
• Consider imaging of chest and abdomen to exclude fungal infection or abscesses if fever persists beyond 4-6 days 1

Duration of Therapy

Standard Duration

• Continue antibiotics for documented bacterial meningitis per identified pathogen and clinical response 1
• For viral encephalitis, high-dose aciclovir should continue for full treatment course 1

Monitoring After Treatment

• Patients must be monitored closely after antibiotic discontinuation, with prompt reinitiation if fever recurs 8

Critical Pitfalls to Avoid

Common Errors

• Delaying lumbar puncture in altered mental status patients can miss treatable meningitis/encephalitis 1
• Withholding antibiotics while awaiting diagnostic results increases mortality in severe bacterial infections 4
• Assuming normal WBC excludes bacterial infection; CRP is a better indicator when WBC response is blunted 7
• Failing to cover Listeria monocytogenes in CNS infections (requires ampicillin or meropenem, not ceftriaxone alone) 1

Special Considerations

• If this patient has underlying immunosuppression, hematologic malignancy, or recent chemotherapy, consider febrile neutropenia protocols even with borderline-normal WBC 4
• CRP velocity (rate of rise) may help distinguish bacterial from viral: bacterial infections typically show CRP velocity >1 mg/L/hour 3