What is the most important treatment for a 50-year-old man with confusion, unable to communicate, intubated, with fever (hyperthermia), hypotension, tachycardia, tachypnea, and cerebrospinal fluid (CSF) analysis showing predominantly mononuclear cells, elevated lactate (lactic acid) count, and elevated protein, with negative gram stain?

Immediate Empiric Treatment for Suspected Meningoencephalitis

Start IV acyclovir 10 mg/kg every 8 hours immediately, along with empiric antibiotics (vancomycin plus ceftriaxone plus ampicillin), and strongly consider empiric anti-tuberculous therapy given the CSF profile showing mononuclear predominance with low glucose. 1, 2

Critical Initial Management

The CSF findings—mononuclear cell predominance, elevated protein (150 mg/dL), and low glucose (50 mg/dL)—create a diagnostic emergency requiring simultaneous coverage of multiple life-threatening conditions:

Acyclovir Must Be Started Immediately

• Acyclovir 10 mg/kg IV every 8 hours is the single most important treatment because HSV encephalitis is the most critical treatable cause of viral encephalitis, and delays in treatment significantly increase mortality and morbidity 1, 3
• Start acyclovir immediately even before CSF PCR results are available, as delays worsen outcomes 1
• Never delay acyclovir while awaiting imaging or diagnostic results—the mortality benefit is time-dependent 1
• Initial CSF PCR can be negative in 5-10% of HSV encephalitis cases, particularly if obtained early or late in illness, so treatment should not be withheld based on initial negative results 1

Empiric Antibiotics Are Essential

• Add vancomycin plus ceftriaxone plus ampicillin immediately until bacterial meningitis is definitively excluded 2, 4
• The negative Gram stain does NOT exclude bacterial meningitis—Gram stain sensitivity is only 50-99% depending on organism and prior antibiotics 5
• Ampicillin is critical because Listeria monocytogenes accounts for 20-40% of bacterial meningitis in patients over 50 years and presents with lymphocytic pleocytosis and low glucose, mimicking this exact presentation 4
• Listeria is resistant to cephalosporins, making ampicillin mandatory in this age group 4

Tuberculous Meningitis Must Be Considered

• The combination of mononuclear predominance, low glucose, and markedly elevated protein (150 mg/dL) is highly characteristic of TB meningitis 2, 4
• A two-day history of confusion represents a subacute presentation that fits the typical indolent course of TB meningitis 4
• Start empiric four-drug anti-tuberculous therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) immediately without waiting for microbiological confirmation, as delays worsen outcomes 2, 4
• CSF AFB smear sensitivity is only 10-20%, so negative results do not exclude TB meningitis 4

Why This CSF Profile Is Diagnostically Challenging

The low CSF glucose (50 mg/dL) is the critical finding that distinguishes this case from typical viral encephalitis:

• Viral encephalitis typically presents with normal or only slightly low CSF glucose, with CSF/plasma glucose ratio remaining above 0.36 5, 1
• A CSF/plasma glucose ratio <0.5 strongly suggests TB meningitis, fungal infection, or partially treated bacterial meningitis 2, 4
• Mononuclear predominance can occur in partially treated bacterial meningitis if antibiotics were given before lumbar puncture 5, 2
• Listeria meningitis characteristically presents with lymphocytic pleocytosis and low glucose in elderly patients, mimicking this exact presentation 4

Essential Diagnostic Workup

While treatment is being initiated, obtain:

• CSF PCR for HSV-1, HSV-2, VZV, and enterovirus 1
• CSF AFB smear, TB culture, and TB PCR (send 6 mL of CSF for optimal yield) 2
• CSF bacterial culture and repeat Gram stain 2
• Simultaneous plasma glucose measurement to calculate CSF/plasma glucose ratio, which is more diagnostically useful than absolute CSF glucose values 2
• CSF lactate level <2 mmol/L can effectively rule out bacterial disease 2
• HIV testing, as HIV increases risk of both TB meningitis and opportunistic infections 4
• Brain MRI with contrast to identify basilar meningeal enhancement characteristic of TB meningitis 4

Critical Pitfalls to Avoid

• Never stop acyclovir based on a single negative CSF PCR if clinical suspicion remains high; repeat LP at 24-48 hours 1
• Do not assume viral meningitis based on mononuclear predominance alone—57% of aseptic meningitis cases have PMN predominance, and conversely, partially treated bacterial meningitis and Listeria can show lymphocytic predominance 6, 5
• The absolute CSF glucose value can be misleading when serum glucose is abnormal—always calculate the CSF/plasma glucose ratio 2
• Do not delay treatment while awaiting culture results—CSF sterilization can occur within hours of antibiotic administration, but treatment must not be delayed 5
• Do not use corticosteroids as monotherapy in suspected viral encephalitis 1

Hemodynamic Instability Requires Concurrent Management

The patient's hypotension (90/60 mmHg) and tachycardia (HR 101) indicate septic shock:

• Aggressive fluid resuscitation and vasopressor support are needed alongside antimicrobial therapy 5
• The combination of fever, hypotension, and altered mental status represents severe sepsis requiring ICU-level care 5

Duration of Therapy

• Acyclovir should continue for 14-21 days if HSV encephalitis is confirmed 1, 3
• Anti-tuberculous therapy requires 12 months total (2 months of four-drug therapy followed by 10 months of two-drug continuation) if TB meningitis is confirmed 2
• Bacterial meningitis treatment duration depends on organism identified but typically ranges from 10-14 days for most pathogens 5