What is the best course of action for a patient with acute altered mental status, leukocytosis, and impaired renal function, who is currently being treated with meropenem and has no fever?

Management of Acute Altered Mental Status with Leukocytosis and Renal Impairment on Meropenem Without Fever

Continue meropenem with dose adjustment for renal function and aggressively investigate non-infectious causes of altered mental status, as absence of fever does not exclude serious infection but mandates broader differential consideration.

Initial Stabilization and Assessment

• Ensure airway protection immediately and transfer to a monitored ICU setting given the severity of presentation with altered mental status and multiorgan involvement 1
• Assess mental status severity using the Glasgow Coma Scale to objectively quantify impairment and guide management intensity 1, 2
• If intubation is required, use short-acting sedatives like propofol or dexmedetomidine rather than benzodiazepines 1, 3

Critical Diagnostic Considerations

The absence of fever does NOT rule out serious infection. In elderly patients and those with renal impairment, fever may be absent despite severe infection 4. However, altered mental status with leukocytosis demands investigation of multiple etiologies:

Infectious Causes to Consider

• Meningitis/encephalitis: Elderly patients are more likely to present with altered consciousness than fever or neck stiffness 4
• Occult sepsis: Leukocytosis with altered mental status may represent sepsis even without fever 4
• Obtain head CT without contrast as first-line imaging for new altered mental status 1
• Consider lumbar puncture if no contraindications exist and meningitis remains in differential 4

Non-Infectious Causes (Must Evaluate)

• Uremic encephalopathy: Given impaired renal function, assess BUN, creatinine, and metabolic acidosis 4
• Drug-related: Meropenem itself can cause altered mental status, especially with renal impairment and accumulation 5, 6
• Metabolic derangements: Check comprehensive metabolic panel, calcium, glucose, ammonia if cirrhosis suspected 1
• Bowel obstruction/ischemia: Leukocytosis with altered mental status can indicate intestinal ischemia; examine for peritoneal signs 4

Meropenem Management in Renal Impairment

Meropenem dosing MUST be adjusted for renal function to prevent neurotoxicity while maintaining efficacy:

• Meropenem half-life increases from 1 hour (normal) to up to 13.7 hours in anuric patients 7
• Therapeutic drug monitoring (TDM) is strongly recommended in this clinical scenario combining renal impairment and altered mental status 6, 8
• Target trough concentrations of 8-16 mg/L for optimal efficacy without toxicity 8
• Patients with severe renal impairment show dose-normalized exposure 3-5 times higher than those with normal function 8

Specific Dosing Guidance

• If on continuous renal replacement therapy (CRRT): Consider 1g IV every 12 hours as initial dose 9
• Approximately 25-50% of meropenem is eliminated by continuous venovenous hemofiltration 7
• Risk of underdosing exists with CRRT, but neurotoxicity risk increases with renal impairment 7, 10

Management Algorithm

1. Immediate actions:

   • Stabilize airway and transfer to monitored setting 1
   • Obtain comprehensive labs: CBC, CMP, renal/liver function, lactate, blood cultures 1
   • Head CT without contrast 1
   • Measure meropenem trough level if available 6, 8

2. Continue empiric antibiotics while investigating:

   • Maintain meropenem but adjust dose for renal function 5, 7
   • Do NOT discontinue antibiotics based solely on absence of fever 4
   • Consider adding empiric acyclovir 10 mg/kg IV three times daily if encephalitis possible 1

3. Investigate alternative causes:

   • Assess for uremic encephalopathy (BUN, creatinine) 4
   • Evaluate for drug accumulation (meropenem levels) 6, 8
   • Rule out bowel ischemia if abdominal signs present 4
   • Consider hepatic encephalopathy if cirrhosis history 3

4. Adjust meropenem based on findings:

   • If meropenem levels elevated or neurotoxicity suspected: reduce dose or extend interval 7, 8
   • If levels subtherapeutic: increase dose or frequency 10, 8
   • If alternative diagnosis confirmed and infection ruled out: consider discontinuation

Critical Pitfalls to Avoid

• Do not assume absence of fever excludes infection in elderly or renally impaired patients 4
• Do not continue standard meropenem dosing without adjustment for renal function—this risks seizures and neurotoxicity 5, 7
• Do not attribute altered mental status to infection alone without investigating metabolic, drug-related, and structural causes 1, 2
• Do not delay lumbar puncture if meningitis/encephalitis remains possible after imaging 4
• Avoid relying on Kernig's or Brudzinski's signs, which have poor sensitivity 4

Monitoring Requirements

• Serial neurological assessments every 2-4 hours 3
• Daily renal function and electrolytes 1
• Meropenem trough levels if TDM available 6, 8
• Vital signs including temperature trends (fever may develop later) 4
• Urine output monitoring with Foley catheter 4