Treatment of Cryptococcosis in HIV Patients with Blurred Vision and Muscle Weakness
The treatment of choice for HIV patients with cryptococcosis presenting with blurred vision and muscle weakness is amphotericin B deoxycholate (0.7-1.0 mg/kg/day) plus flucytosine (100 mg/kg/day) for 2 weeks as induction therapy, followed by fluconazole 400 mg daily for 8 weeks as consolidation therapy, and then fluconazole 200 mg daily for maintenance. 1
Initial Assessment and Management
Urgent Evaluation
- Obtain brain imaging (CT or MRI) before lumbar puncture to rule out mass lesions
- Measure CSF opening pressure in lateral decubitus position (normal <25 cm H2O)
- Check serum cryptococcal antigen (positive in >99% of cryptococcal meningitis cases)
- Perform lumbar puncture for:
- CSF cryptococcal antigen
- Fungal culture
- Cell count, protein, and glucose levels
Management of Increased Intracranial Pressure
- For patients with blurred vision, papilledema, or other signs of increased intracranial pressure:
Antifungal Treatment Protocol
Induction Phase (First 2 weeks)
First-line regimen:
- Amphotericin B deoxycholate (0.7-1.0 mg/kg/day IV) plus
- Flucytosine (100 mg/kg/day orally in 4 divided doses) 1
Alternative if renal concerns exist:
- Liposomal amphotericin B (3-4 mg/kg/day IV) or
- Amphotericin B lipid complex (5 mg/kg/day IV) plus
- Flucytosine (100 mg/kg/day) 1
If flucytosine is unavailable/not tolerated:
- Amphotericin B plus fluconazole (800 mg/day) 1
Consolidation Phase (8 weeks)
- Fluconazole 400 mg daily orally 1
- Perform repeat lumbar puncture after 2 weeks of therapy to ensure CSF sterilization 1
Maintenance Phase
- Fluconazole 200 mg daily orally
- Continue until immune reconstitution occurs with ART (CD4 ≥100 cells/μL and undetectable viral load for ≥3 months) with minimum of 1 year of antifungal therapy 1
Managing Complications
For Cerebral Cryptococcomas
If imaging reveals cryptococcomas (more likely with blurred vision):
- Extend induction therapy to at least 6 weeks 1
- Consider corticosteroids for mass effect and surrounding edema 1
- For large lesions (≥3 cm) with mass effect, consider surgical debulkment 1
For Immune Reconstitution Inflammatory Syndrome (IRIS)
- Continue antifungal therapy without alteration 1
- For severe CNS inflammation with increased ICP, consider corticosteroids (0.5-1.0 mg/kg/day of prednisone equivalent) 1
- Delay initiation of ART until completion of induction therapy (first 2 weeks) 1
Monitoring During Treatment
Amphotericin B Monitoring
- Preinfusion administration of 500 mL normal saline to reduce nephrotoxicity 1
- Monitor for electrolyte abnormalities, especially potassium and magnesium
- Monitor renal function regularly
- Premedicate with acetaminophen and diphenhydramine to reduce infusion reactions 1
Flucytosine Monitoring
- Monitor blood levels (peak levels should not exceed 75 μg/mL) 1
- Check complete blood count for bone marrow suppression
- Monitor for gastrointestinal toxicity
Treatment Failure Management
If no improvement after 2 weeks or relapse occurs:
- For patients initially on fluconazole, switch to amphotericin B with or without flucytosine 1
- Consider liposomal amphotericin B (4-6 mg/kg/day) for treatment failures 1
- Higher doses of fluconazole with flucytosine may be considered 1
Key Pitfalls to Avoid
Failing to manage increased intracranial pressure - This is a major cause of early mortality and must be addressed aggressively 1
Confusing treatment failure with IRIS - Approximately 30% of patients develop IRIS after starting ART; this requires anti-inflammatory treatment, not changing antifungal therapy 1
Starting ART too early - Delaying ART until after induction therapy (2 weeks) is recommended to reduce risk of severe IRIS 1
Inadequate monitoring of drug toxicities - Both amphotericin B and flucytosine require careful monitoring to prevent serious adverse effects 1
Stopping maintenance therapy too early - Maintenance therapy should continue until adequate immune reconstitution occurs 1