What is the recommended treatment for a 50-year-old non-HIV individual diagnosed with cryptococcal meningitis?

Treatment of Cryptococcal Meningitis in a 50-Year-Old Non-HIV Individual

For a 50-year-old non-HIV patient with cryptococcal meningitis, initiate induction therapy with 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, followed by consolidation therapy with fluconazole (400 mg/day) for 8-10 weeks, then maintenance therapy with fluconazole (200 mg/day) for 6-12 months. 1, 2

Induction Phase (First 2-6 Weeks)

Primary Regimen

• Amphotericin B deoxycholate 0.7-1.0 mg/kg/day IV plus flucytosine 100 mg/kg/day orally (divided into 4 doses) for a minimum of 2 weeks 1, 2
• The duration of induction remains debated: some experts favor 2 weeks (similar to HIV patients), while others support 4-6 weeks for non-HIV patients 1
• Perform a repeat lumbar puncture at 2 weeks to document CSF sterilization 1, 2
• If CSF cultures remain positive at 2 weeks, extend induction therapy to 4-6 weeks 1

Alternative Regimens for Renal Dysfunction

• Liposomal amphotericin B (3-4 mg/kg/day IV) plus flucytosine (100 mg/kg/day) for patients with baseline renal impairment or developing nephrotoxicity 1
• Amphotericin B lipid complex (ABLC) 5 mg/kg/day IV plus flucytosine is another option for renal concerns 1
• Liposomal amphotericin B at 4 mg/kg/day achieves faster CSF sterilization than standard amphotericin B and has equivalent efficacy with less toxicity 1

Critical Monitoring During Induction

• Administer 500 mL normal saline pre-infusion with amphotericin B to reduce nephrotoxicity 1
• Monitor serum flucytosine levels 2 hours post-dose, targeting 30-80 μg/mL to prevent bone marrow suppression 1, 2
• Check complete blood counts, renal function, and electrolytes at least twice weekly 2, 3
• Measure opening pressure at every lumbar puncture in the lateral decubitus position (normal <25 cm H₂O) 1, 2

Consolidation Phase (8-10 Weeks)

• Fluconazole 400 mg daily orally for 8-10 weeks after completing induction therapy 1, 2
• This phase begins after documented CSF sterilization (negative culture at 2 weeks) 1
• For immunosuppressed non-HIV patients (e.g., on chronic corticosteroids), consider higher doses of fluconazole 400-800 mg daily 1

Maintenance Phase (6-12 Months)

• Fluconazole 200 mg daily orally for 6-12 months 1, 2
• This extended maintenance is critical because relapse rates in non-HIV patients historically ranged 15-25%, primarily occurring in the first year 1
• For patients on long-term immunosuppression, maintenance may need to continue longer than 12 months 1

Management of Increased Intracranial Pressure

Aggressive management of elevated intracranial pressure is mandatory and directly impacts mortality. 1, 2

• If opening pressure >25 cm H₂O or patient has confusion, blurred vision, papilledema, or focal neurologic signs, perform daily therapeutic lumbar punctures 1, 2
• Remove sufficient CSF (typically 20-30 mL) to reduce opening pressure by approximately 50% 1
• Continue daily lumbar punctures until pressure normalizes 1, 4
• Consider ventriculoperitoneal shunt placement if daily lumbar punctures are no longer tolerated or symptoms persist despite aggressive drainage 1
• Do not use corticosteroids, mannitol, or acetazolamide for managing increased intracranial pressure in cryptococcal meningitis 1

Critical Pitfalls to Avoid

Inadequate Induction Therapy

• Never use fluconazole alone or fluconazole plus flucytosine as primary induction therapy in non-HIV patients—a polyene (amphotericin B formulation) must be included 1
• Fluconazole monotherapy is associated with unacceptably high morbidity and mortality in this population 1

Failure to Document CSF Sterilization

• Do not rely on cryptococcal antigen titers, India ink results, or CSF chemistry/cell counts alone to assess treatment response 1, 2
• Only negative CSF cultures definitively indicate microbiological response 1
• Persistent positive cultures after 4 weeks of adequate therapy defines treatment failure and requires regimen modification 1

Inadequate Pressure Management

• Elevated intracranial pressure was associated with death in 93% of early deaths (within 2 weeks) in major trials 1
• Failure to measure opening pressure at diagnosis and during follow-up is a critical error 2

Premature Discontinuation

• Most relapses result from inadequate primary therapy duration or poor compliance with consolidation/maintenance fluconazole 1
• The historical 15-25% relapse rate in non-HIV patients emphasizes the need for full-duration therapy 1

Special Considerations for Immunosuppressed Non-HIV Patients

• If patient is on chronic corticosteroids, attempt to reduce to ≤10 mg prednisone daily (or equivalent) if medically feasible 1
• For solid organ transplant recipients or those on other immunosuppressants, consider the longer 4-6 week induction regimen rather than 2 weeks 1
• These patients may require more prolonged consolidation (up to 1 year) and extended or indefinite maintenance therapy 1

Monitoring Treatment Response

• Repeat lumbar puncture at 2 weeks to confirm CSF sterilization 1, 2
• If cultures remain positive at 2 weeks, this predicts higher relapse risk and warrants extended induction therapy 1
• Perform additional lumbar punctures if new symptoms develop during or after treatment to distinguish relapse from other complications 1, 2
• Serial CSF cultures are the gold standard for monitoring—not antigen titers 1, 2