What are the dose, duration, and route of antifungal therapy for candidiasis?

Antifungal Therapy for Candidiasis: Dose, Duration, and Route

For invasive candidiasis and candidemia, initiate an echinocandin (caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily) intravenously for 2 weeks after blood culture clearance and symptom resolution, with catheter removal strongly recommended. 1

Candidemia and Invasive Candidiasis

First-Line Therapy

• Echinocandins are preferred for most patients, particularly those who are critically ill, have recent azole exposure, or are at risk for C. glabrata or C. krusei infection 1:
  • Caspofungin: 70 mg IV loading dose, then 50 mg IV daily 1
  • Micafungin: 100 mg IV daily 1, 2
  • Anidulafungin: 200 mg IV loading dose, then 100 mg IV daily 1

Alternative Therapy

• Fluconazole (800 mg [12 mg/kg] loading dose, then 400 mg [6 mg/kg] daily IV or PO) is acceptable for less critically ill patients without recent azole exposure and not colonized with azole-resistant species 1, 3
• Liposomal amphotericin B (3-5 mg/kg IV daily) is reserved for intolerance to other agents 1

Duration and Catheter Management

• Continue therapy for 2 weeks after first negative blood culture and resolution of symptoms 1
• Remove central venous catheters in nonneutropenic patients (strongly recommended) 1
• Consider catheter removal in neutropenic patients 1

Species-Specific Considerations

• C. glabrata: Echinocandin preferred; liposomal amphotericin B is alternative 1
• C. parapsilosis: Fluconazole or liposomal amphotericin B preferred over echinocandins (echinocandins have reduced activity) 1
• C. krusei: Echinocandin, liposomal amphotericin B, or voriconazole (fluconazole-resistant) 1

Site-Specific Infections

CNS Candidiasis (Meningitis)

• Liposomal amphotericin B 5 mg/kg IV daily with or without flucytosine 25 mg/kg PO/IV four times daily 1
• Step-down to fluconazole 400-800 mg (6-12 mg/kg) daily for susceptible isolates after clinical response 1
• Continue until all signs, symptoms, CSF abnormalities, and radiological findings resolve 1
• Remove infected CNS devices (ventriculostomy drains, shunts) if possible 1

Endocarditis

• Native valve: Liposomal amphotericin B 3-5 mg/kg IV daily with or without flucytosine 25 mg/kg four times daily, OR high-dose echinocandin (caspofungin 150 mg daily, micafungin 150 mg daily, or anidulafungin 200 mg daily) 1
• Step-down to fluconazole 400-800 mg (6-12 mg/kg) daily for susceptible isolates after clinical stability and bloodstream clearance 1
• Valve replacement is recommended; continue therapy for at least 6 weeks post-surgery (longer if perivalvular abscesses present) 1
• Long-term suppression with fluconazole 400-800 mg daily if valve replacement not possible 1

Intra-Abdominal Candidiasis

• Source control with drainage/debridement is essential 1
• Antifungal choice same as candidemia (echinocandin preferred) 1
• Duration determined by adequacy of source control and clinical response 1

Urinary Tract Infections

• Asymptomatic cystitis: Usually no treatment needed; eliminate predisposing factors 1
• Symptomatic cystitis: Fluconazole 200 mg (3 mg/kg) daily for 14 days 1, 4
• Pyelonephritis: Fluconazole 200-400 mg (3-6 mg/kg) daily for 14 days 1, 4
• Alternative: Amphotericin B deoxycholate 0.3-0.6 mg/kg/day with or without flucytosine for 7-14 days 1

Mucocutaneous Candidiasis

Oropharyngeal Candidiasis

• Mild disease: Clotrimazole troches 10 mg five times daily for 7-14 days, OR miconazole mucoadhesive buccal tablet 50 mg once daily for 7-14 days, OR nystatin suspension 4-6 mL four times daily for 7-14 days 4
• Moderate to severe: Fluconazole 200 mg on day 1, then 100 mg daily for 7-14 days 1, 4, 3

Esophageal Candidiasis

• Fluconazole 200-400 mg daily for 14-21 days (minimum 3 weeks, at least 2 weeks after symptom resolution) 1, 3
• Alternative: Amphotericin B deoxycholate 0.3-0.7 mg/kg/day IV 1
• Alternative: Echinocandin or voriconazole 1

Vulvovaginal Candidiasis

• Uncomplicated: Fluconazole 150 mg PO as single dose 4, 3
• Severe acute: Fluconazole 150 mg every 72 hours for 2-3 doses total 4
• Recurrent: Initial induction with 10-14 days topical agent or oral fluconazole, followed by fluconazole 150 mg weekly for 6 months 4

Endophthalmitis

• Amphotericin B deoxycholate 0.7-1 mg/kg with flucytosine, OR fluconazole, OR liposomal amphotericin B, OR voriconazole, OR echinocandin 1
• Duration at least 4-6 weeks, determined by repeated examinations to verify resolution 1
• Surgical intervention for severe endophthalmitis or vitreitis 1

Special Populations

Neonates

• Amphotericin B deoxycholate 1 mg/kg IV daily is first-line 1
• Fluconazole 12 mg/kg IV or PO daily is reasonable alternative (not if on fluconazole prophylaxis) 1
• Liposomal amphotericin B 3-5 mg/kg daily (use with caution, particularly with urinary tract involvement) 1
• Duration: 3 weeks for candidemia without metastatic complications 1
• Lumbar puncture and dilated retinal examination recommended for all neonates with positive blood/urine cultures 1
• Imaging of genitourinary tract, liver, and spleen if blood cultures persistently positive 1

Neutropenic Patients

• Empiric therapy: Echinocandin preferred, OR liposomal amphotericin B 3-5 mg/kg daily, OR caspofungin, OR voriconazole (if additional mold coverage desired) 1
• Do not use azoles if patient received azole prophylaxis 1
• Continue therapy for 2 weeks after neutropenia resolution and bloodstream clearance 1

ICU Patients (Empiric Therapy)

• Echinocandin preferred for critically ill patients with risk factors and no other fever cause 1
• Fluconazole 800 mg loading dose, then 400 mg daily acceptable if no recent azole exposure and not colonized with azole-resistant species 1
• Start empiric therapy as soon as possible in patients with septic shock 1
• Duration: 2 weeks if clinical improvement 1
• Stop therapy at 4-5 days if no clinical response and no subsequent evidence of invasive candidiasis 1

Critical Pitfalls to Avoid

• Do not use fluconazole empirically in patients with recent azole exposure, critically ill patients, or those at high risk for C. glabrata or C. krusei 1
• Echinocandins have reduced activity against C. parapsilosis—consider fluconazole or liposomal amphotericin B for this species 1
• Candida isolated from respiratory secretions usually represents colonization and rarely requires treatment 1
• Inadequate treatment duration leads to recurrence—ensure full course completion based on clinical and microbiological response 3
• For denture-related oropharyngeal candidiasis, disinfect dentures in addition to antifungal therapy to prevent treatment failure 4