What are the recommended treatments for fungal infections?

Antifungal Medications: Treatment Recommendations by Infection Type

Invasive Candidiasis and Candidemia

For invasive candidiasis and candidemia, an echinocandin is the first-line treatment of choice, with caspofungin (70 mg loading dose, then 50 mg daily), micafungin (100 mg daily), or anidulafungin (200 mg loading dose, then 100 mg daily) recommended as initial therapy. 1

Initial Treatment Selection

• Echinocandins are preferred for critically ill patients and those with recent azole exposure due to their fungicidal activity and superior safety profile 1, 2
• Fluconazole (800 mg loading dose, then 400 mg daily) is an acceptable alternative only for non-critically ill patients unlikely to have fluconazole-resistant species 1
• Treatment duration should be at least 14 days following resolution of symptoms or last positive culture, whichever is longer 3

Species-Specific Considerations

• For C. glabrata infections: Echinocandins are strongly preferred due to high rates of azole resistance; do not transition to fluconazole without confirmed susceptibility testing 2
• For C. krusei: Use amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days, as this species has intrinsic fluconazole resistance 1
• Susceptibility testing is mandatory for all bloodstream and clinically relevant Candida isolates 1

Step-Down Therapy

• Transition from echinocandin to fluconazole (400 mg daily) is appropriate once the patient is clinically stable and the isolate is confirmed susceptible 2
• This transition typically occurs after clinical improvement and documented clearance on repeat blood cultures 2

Oropharyngeal and Esophageal Candidiasis

Oropharyngeal Candidiasis

• For mild disease: Clotrimazole troches 10 mg 5 times daily for 7-14 days 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 for up to 28 days 1

Esophageal Candidiasis

• Fluconazole 200-400 mg daily is the treatment of choice for 14-21 days until clinical improvement 1
• Alternative options include itraconazole 200 mg daily, echinocandins, or voriconazole for refractory cases 1
• Patients should be treated for a minimum of 14 days and at least 7 days following resolution of symptoms 3

Urinary Tract Candidiasis

Cystitis

• For symptomatic cystitis: Fluconazole 200 mg (3 mg/kg) daily for 14 days 1
• For fluconazole-resistant species (C. glabrata, C. krusei): Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days OR oral flucytosine 25 mg/kg 4 times daily for 7-10 days 1
• Catheter removal is essential if feasible, as this significantly improves outcomes 1

Pyelonephritis

• Fluconazole 200-400 mg (3-6 mg/kg) daily for 14 days for fluconazole-susceptible organisms 1
• For fluconazole-resistant C. glabrata: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days with or without flucytosine 1
• Elimination of urinary tract obstruction and removal/replacement of nephrostomy tubes or stents is strongly recommended 1

Invasive Aspergillosis

Voriconazole is the treatment of choice for invasive aspergillosis, with a loading dose of 6 mg/kg IV every 12 hours for the first 24 hours, followed by 4 mg/kg IV every 12 hours as maintenance. 3

• Once clinically improved, transition to oral voriconazole 200 mg every 12 hours (equivalent to 3 mg/kg IV) or 300 mg every 12 hours (equivalent to 4 mg/kg IV) 3
• Alternative agents include lipid formulation amphotericin B (3-5 mg/kg daily) or echinocandins for salvage therapy 1
• Treatment should continue until resolution or stabilization of all clinical and radiographic manifestations 1

Superficial Fungal Infections (Dermatophytes)

Topical Therapy

• Fungicidal agents are preferred over fungistatic agents: terbinafine, naftifine, or butenafine applied once daily for 1 week achieve high cure rates 4
• Azole agents (miconazole, clotrimazole, ketoconazole) are fungistatic and require longer treatment courses but work well for Candida skin infections 4

Systemic Therapy for Extensive Infections

• For extensive or severe fungal infections of the beard: Fluconazole 150-200 mg once daily for 2-4 weeks 5
• For widespread dermatophyte infections: Oral griseofulvin, ketoconazole, or itraconazole may be required 6

Critical Management Principles

Source Control

• Remove all infected central venous catheters in non-neutropenic patients with candidemia 2
• Remove indwelling bladder catheters whenever feasible for urinary candidiasis 1

Monitoring Requirements

• Perform follow-up blood cultures to document clearance of candidemia 2
• For disseminated infections, follow-up imaging is essential to confirm resolution of lesions 2
• Regular clinical assessment for improvement of symptoms and signs of infection 2

Common Pitfalls to Avoid

• Do not use fluconazole empirically in critically ill patients or those with recent azole exposure without susceptibility data 1
• Do not assume azole susceptibility in C. glabrata—always obtain susceptibility testing before transitioning from echinocandin therapy 2
• Do not rely on topical therapy alone for nail infections or hair follicle infections—these require systemic treatment 4
• Ensure adequate treatment duration; premature discontinuation leads to recurrence, especially with fungistatic agents 4