What conditions are treated by Amphotericin B (AmB) deoxycholate and Flucytosine?

Treatment Indications for Amphotericin B Deoxycholate and Flucytosine

The combination of amphotericin B deoxycholate and flucytosine is the gold-standard induction therapy for cryptococcal meningoencephalitis and other serious invasive cryptococcal infections, as well as severe systemic candidiasis including endocarditis, CNS infections, and endophthalmitis. 1

Primary Indication: Cryptococcal Disease

Cryptococcal Meningoencephalitis

• This combination represents the strongest evidence-based regimen for CNS cryptococcal disease, with amphotericin B deoxycholate 0.7-1.0 mg/kg/day IV plus flucytosine 100 mg/kg/day orally (divided into 4 doses) for at least 2 weeks as induction therapy 1
• The combination achieves more rapid CSF sterilization compared to amphotericin B alone (p < 0.001) and reduces treatment failures and relapses 2
• This regimen is recommended with the highest level of evidence (A-I rating) by the Infectious Diseases Society of America 1
• After successful 2-week induction (defined as clinical improvement and negative CSF culture), transition to fluconazole 400 mg daily for 8 weeks consolidation 1

Other Cryptococcal Manifestations

• Severe non-meningeal cryptococcosis including cryptococcemia, disseminated disease (≥2 noncontiguous sites), and severe pulmonary cryptococcosis should be treated identically to CNS disease for 12 months 1
• High fungal burden disease (e.g., cryptococcal antigen titer ≥1:512) warrants the same aggressive combination approach 1

Special Populations

• HIV-infected patients: Standard dosing with HAART initiation delayed 2-10 weeks after starting antifungals to reduce IRIS risk 1
• Organ transplant recipients: Liposomal amphotericin B 3-4 mg/kg/day is preferred over deoxycholate formulation due to concurrent nephrotoxic immunosuppressants, but flucytosine remains essential 1

Secondary Indication: Invasive Candidiasis

Candida CNS Infections

• Candida meningitis and ventriculitis require amphotericin B combined with flucytosine due to flucytosine's superior blood-brain barrier penetration 1, 3
• Therapy continues until CSF normalization, radiological resolution, and neurological stabilization 1

Candida Endocarditis

• The combination is indicated for Candida endocarditis, with flucytosine providing enhanced penetration into cardiac vegetations 4, 3
• Treatment requires minimum 4 weeks after resolution of all signs and symptoms, plus removal of prosthetic devices 1

Candida Endophthalmitis

• Sight-threatening candidal eye infections benefit from flucytosine's excellent ocular penetration when combined with amphotericin B 1, 3
• All candidemia patients require dilated retinal examination by ophthalmology to detect this complication 1

Other Candida Infections

• Candida septicemia and urinary tract infections are FDA-approved indications, though less commonly requiring combination therapy unless severe or refractory 4
• Limited data support use in pulmonary candidiasis 4

Critical Dosing and Monitoring Requirements

Flucytosine Specifics

• Standard dose: 25 mg/kg orally four times daily (total 100 mg/kg/day) for normal renal function 1, 3
• Mandatory therapeutic drug monitoring: Target serum levels 40-60 mg/mL to minimize concentration-dependent bone marrow toxicity 1, 3
• Renal dose adjustment is essential as flucytosine is renally excreted 3, 4
• Monitor complete blood counts for myelosuppression 1

Amphotericin B Deoxycholate Specifics

• Cryptococcal disease: 0.7-1.0 mg/kg/day IV (use 0.7-1.0 mg/kg in combination; 1 mg/kg if monotherapy) 1
• Candida infections: Dosing per FDA label for specific indication 5
• Monitor renal function closely; consider lipid formulations if creatinine rises 1

Absolute Contraindications and Pitfalls

Never Use Flucytosine as Monotherapy

• Flucytosine monotherapy rapidly induces resistance and is absolutely contraindicated 3, 4
• This is the single most critical error to avoid in clinical practice 3

Availability Limitations

• Flucytosine is only available orally in the United States, limiting use in patients unable to take oral medications 3
• IV formulations exist in some countries and may be used for severe cases 1

Managing Intracranial Pressure in Cryptococcal Meningitis

• Elevated ICP (>25 cm H2O) is the most critical determinant of outcome, not just antifungal therapy 1
• Perform daily therapeutic lumbar punctures to reduce opening pressure by 50% until stabilized 1
• Avoid acetazolamide and corticosteroids for ICP management (unless treating IRIS) 1
• Consider temporary lumbar drains or ventriculostomy for refractory cases 1

Drug Interactions and Toxicity

• The combination shows less nephrotoxicity than amphotericin B alone (p < 0.05) 2
• Flucytosine adverse reactions occur in approximately 32% of patients but are rarely life-threatening 2
• Bone marrow suppression is the primary concern with flucytosine, necessitating CBC monitoring 1