Cryptococcus (microregistrar.moodlecloud)
drsuryabrata@gmail.com🦠 Cryptococcosis Treatment Algorithm
Global Guidelines for Diagnosis and Management | Evidence-Based Recommendations
Based on the Global Guideline for the Diagnosis and Management of Cryptococcosis (Lancet Infectious Diseases, 2024)
🧠 CNS Cryptococcosis
HIV
SOT
Non-HIV/Non-SOT
C. gattii
Cryptococcoma
🔄 Disseminated Disease
(Non-CNS/Non-pulmonary)
🫁 Pulmonary Disease
Severe
Mild
With/Without Cryptococcoma
🩹 Direct Skin Inoculation
Cutaneous infection
💊 PRIMARY INDUCTION THERAPY
🏥 High-Income Settings (AIIt):
Liposomal Amphotericin B 3-4 mg/kg daily + Flucytosine 25 mg/kg four times daily
🌍 Low-Income Settings (AI):
Single-dose Liposomal AmB 10 mg/kg + Flucytosine 25 mg/kg four times daily + Fluconazole 1200 mg daily × 14 days
⬇️
🎯 INDUCTION PHASE
HIV: 2 weeks
SOT: ≥2 weeks
Non-HIV: ≥2 weeks
C. gattii: 4-6 weeks
Cryptococcoma: 4-6 weeks
🔄 CONSOLIDATION PHASE
Fluconazole 400-800 mg daily
Duration: 8 weeks
(800 mg preferred in low-income settings)
🛡️ MAINTENANCE PHASE
Fluconazole 200 mg daily
Duration: 12 months
(Until immune restoration)
📋 Treatment Durations by Disease Type
🔄 Disseminated: 2 weeks
🫁 Severe Pulmonary: 2 weeks
🫁 With Cryptococcoma: 4-6 weeks
🫁 Mild Pulmonary: 6-12 months
🩹 Skin Inoculation: 3-6 months
A
Strongly Recommended - High-quality evidence
B
Moderately Recommended - Moderate-quality evidence
⚠️ CRITICAL MANAGEMENT POINTS
🦠 HIV Patients:
• Delay ART initiation 4-6 weeks
• Monitor for C-IRIS
• Screen with CrAg if CD4 <200
• Therapeutic lumbar punctures for ↑ICP
• Delay ART initiation 4-6 weeks
• Monitor for C-IRIS
• Screen with CrAg if CD4 <200
• Therapeutic lumbar punctures for ↑ICP
🏥 SOT Recipients:
• Therapeutic drug monitoring for calcineurin inhibitors
• Carefully adjust immunosuppression
• Monitor for drug-drug interactions
• Extended treatment duration
• Therapeutic drug monitoring for calcineurin inhibitors
• Carefully adjust immunosuppression
• Monitor for drug-drug interactions
• Extended treatment duration
🧠 Raised Intracranial Pressure:
• Therapeutic lumbar punctures if pressure ≥20 cm CSF
• Remove CSF to reduce pressure by 50%
• Surgical drainage if refractory
• Avoid acetazolamide, mannitol
• Therapeutic lumbar punctures if pressure ≥20 cm CSF
• Remove CSF to reduce pressure by 50%
• Surgical drainage if refractory
• Avoid acetazolamide, mannitol
🔬 Drug Monitoring:
• CBC, renal function, electrolytes q48h
• Pre-hydration with amphotericin B
• Aggressive K+ and Mg2+ replacement
• Flucytosine levels if available
• CBC, renal function, electrolytes q48h
• Pre-hydration with amphotericin B
• Aggressive K+ and Mg2+ replacement
• Flucytosine levels if available
🤰 Pregnancy Considerations:
• Amphotericin B formulations are safe
• Avoid flucytosine (Category C)
• Avoid fluconazole (Category D)
• Especially avoid in first trimester
• Amphotericin B formulations are safe
• Avoid flucytosine (Category C)
• Avoid fluconazole (Category D)
• Especially avoid in first trimester
👶 Pediatric Dosing:
• AmB 1 mg/kg or liposomal AmB 3-4 mg/kg
• Flucytosine 100-150 mg/kg/day in 4 doses
• Fluconazole 12 mg/kg daily (max 800 mg)
• Weight-based calculations essential
• AmB 1 mg/kg or liposomal AmB 3-4 mg/kg
• Flucytosine 100-150 mg/kg/day in 4 doses
• Fluconazole 12 mg/kg daily (max 800 mg)
• Weight-based calculations essential
Abbreviations: AmB = Amphotericin B; SOT = Solid Organ Transplant; C-IRIS = Cryptococcosis-associated Immune Reconstitution Inflammatory Syndrome; ICP = Intracranial Pressure; CrAg = Cryptococcal Antigen; CBC = Complete Blood Count
Key Clinical Pearls
- Early Recognition: Consider cryptococcosis in any immunocompromised patient with compatible symptoms, regardless of HIV status
- Lumbar Puncture is Essential: All patients with suspected cryptococcosis require LP with opening pressure measurement
- Combination Therapy Superior: Amphotericin B + flucytosine combination shows superior early fungicidal activity compared to monotherapy
- Pressure Management Critical: Raised intracranial pressure is a major cause of morbidity and mortality - aggressive management with therapeutic LPs is essential
- ART Timing Matters: In HIV patients, delaying ART initiation by 4-6 weeks reduces C-IRIS risk and improves outcomes
Clinical Decision Making
This algorithm represents a synthesis of evidence from multiple randomized controlled trials and expert consensus from over 70 international medical societies. Treatment decisions should always be individualized based on:
- Patient immune status and comorbidities
- Disease severity and extent
- Local antifungal availability and resources
- Potential drug interactions and contraindications
- Monitoring capabilities
When to Consult Specialists
- Infectious Disease: All cases of cryptococcosis
- Neurosurgery: Refractory increased intracranial pressure
- Ophthalmology: Visual changes or suspected ocular involvement
- Clinical Immunology: Cryptococcosis in apparently immunocompetent patients
Remember: Cryptococcosis remains a medical emergency with high mortality. Early recognition, prompt initiation of appropriate antifungal therapy, and aggressive management of complications are crucial for optimal outcomes.
