Treatment of Systemic Fungal Infections

For systemic fungal infections, treatment depends critically on the specific pathogen, site of infection, and patient characteristics, but for invasive candidiasis (the most common systemic fungal infection), an echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred initial therapy for moderately severe to critically ill patients, while amphotericin B formulations remain the gold standard for invasive aspergillosis and CNS infections. 1

Candidemia and Invasive Candidiasis

Initial Therapy Selection

For non-neutropenic adults with candidemia:

Echinocandins are preferred for moderately severe to severe illness or recent azole exposure: caspofungin 70-mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200-mg loading dose then 100 mg daily 1, 2
Fluconazole is appropriate for less critically ill patients without recent azole exposure: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 1
Liposomal amphotericin B 3-5 mg/kg daily is an alternative for patients intolerant of other agents 1

For neutropenic patients:

Fluconazole 800 mg loading dose then 400 mg daily OR an echinocandin OR liposomal amphotericin B 3-5 mg/kg daily 1
Fluconazole is recommended only for patients without recent azole exposure who are not critically ill 1

Critical Management Steps

Remove all intravascular catheters whenever possible (strong recommendation) 1
Obtain daily or every-other-day blood cultures until clearance is documented 1
Perform ophthalmologic examination in all patients with candidemia to detect endophthalmitis 1
Duration: Continue for at least 14 days after the first negative blood culture and resolution of signs/symptoms 1, 2

CNS Candidiasis (Meningitis)

Liposomal amphotericin B 5 mg/kg daily with or without flucytosine 25 mg/kg four times daily is the recommended initial treatment 1

Step-down therapy: Transition to fluconazole 400-800 mg (6-12 mg/kg) daily after clinical response 1
Remove all infected CNS devices (ventriculostomy drains, shunts) if possible 1
Continue therapy until all signs, symptoms, CSF abnormalities, and radiological findings resolve 1

Candida Endophthalmitis

Without Vitritis (Chorioretinitis Only)

For fluconazole/voriconazole-susceptible isolates:

Fluconazole 800 mg loading dose then 400-800 mg daily OR voriconazole 400 mg IV twice daily for 2 doses, then 300 mg IV/oral twice daily 1

For resistant isolates:

Liposomal amphotericin B 3-5 mg/kg IV daily with or without flucytosine 25 mg/kg four times daily 1

With macular involvement: Add intravitreal injection of amphotericin B deoxycholate 5-10 μg/0.1 mL OR voriconazole 100 μg/0.1 mL 1

With Vitritis

Same systemic therapy PLUS intravitreal injection 1
Consider vitrectomy to decrease organism burden and remove inaccessible abscesses 1
Duration: At least 4-6 weeks, with final duration based on repeated ophthalmological examinations showing resolution 1

Invasive Aspergillosis

Voriconazole is the preferred agent (though not explicitly stated in these candidiasis-focused guidelines, amphotericin B formulations remain important) 1, 3

For patients refractory to or intolerant of other therapies:

Caspofungin 70-mg loading dose then 50 mg daily is indicated 2
Liposomal amphotericin B 3-5 mg/kg daily 1
Duration depends on: severity of underlying disease, recovery from immunosuppression, and clinical response 2

Urinary Tract Candidiasis

Asymptomatic Candiduria

Treatment is NOT recommended unless the patient is high-risk 1

High-risk patients requiring treatment:

Neutropenic patients
Very low-birth-weight infants (<1500 g)
Patients undergoing urologic procedures 1

For urologic procedures: Fluconazole 400 mg (6 mg/kg) daily OR amphotericin B deoxycholate 0.3-0.6 mg/kg daily for several days before and after the procedure 1

Symptomatic Cystitis

Fluconazole 200 mg (3 mg/kg) daily for 2 weeks 1

For fluconazole-resistant organisms (e.g., C. glabrata):

Amphotericin B deoxycholate 0.3-0.6 mg/kg for 1-7 days OR flucytosine 25 mg/kg four times daily 1

Pyelonephritis

Fluconazole 200-400 mg (3-6 mg/kg) daily for 2 weeks 1

Alternative: Amphotericin B deoxycholate 0.5-0.7 mg/kg daily with or without flucytosine 25 mg/kg four times daily for 2 weeks 1

If disseminated candidiasis is suspected, treat as candidemia 1

Neonatal Candidiasis

Amphotericin B deoxycholate 1 mg/kg daily is recommended for disseminated candidiasis 1

Fluconazole 12 mg/kg IV/oral daily is a reasonable alternative in patients not on fluconazole prophylaxis 1

Critical evaluations:

Perform lumbar puncture and dilated retinal examination in all neonates with positive cultures 1
CT or ultrasound imaging of genitourinary tract, liver, and spleen if blood cultures remain persistently positive 1
Remove central venous catheters 1
Duration: 2 weeks after documented clearance and resolution of symptoms 1

Mucocutaneous Candidiasis

Oropharyngeal Candidiasis

For mild disease:

Clotrimazole troches 10 mg five times daily for 7-14 days OR miconazole mucoadhesive buccal 50-mg tablet once daily 1
Alternatives: Nystatin suspension 4-6 mL four times daily OR nystatin pastilles 1-2 (200,000 U each) four times daily 1

For moderate to severe disease:

Oral fluconazole 100-200 mg daily for 7-14 days 1

For fluconazole-refractory disease:

Itraconazole solution 200 mg once daily OR posaconazole suspension 400 mg twice daily for 3 days then 400 mg daily 1

Esophageal Candidiasis

Oral fluconazole 200-400 mg (3-6 mg/kg) daily for 14-21 days 1

For patients unable to tolerate oral therapy:

IV fluconazole 400 mg (6 mg/kg) daily OR an echinocandin (micafungin 150 mg daily, caspofungin 70-mg loading then 50 mg daily, or anidulafungin 200 mg daily) 1