What is the first-line treatment for fungal infections?

First-Line Treatment for Fungal Infections

The first-line treatment for fungal infections depends critically on the type of fungus and patient severity: echinocandins (caspofungin, micafungin, or anidulafungin) are first-line for critically ill patients with invasive candidiasis, while fluconazole remains first-line for stable, non-critically ill patients with susceptible Candida species, and voriconazole is first-line for invasive aspergillosis. 1, 2

Invasive Candidiasis (Candidemia)

For Critically Ill or High-Risk Patients

• Echinocandins are the drugs of choice for patients who are hemodynamically unstable, have recent azole exposure, or have high risk of resistant species 1, 2
• Dosing regimens: caspofungin 70 mg loading dose then 50 mg daily; micafungin 100 mg daily; anidulafungin 200 mg loading dose then 100 mg daily 1, 2
• Echinocandins demonstrate fungicidal activity against all Candida species with ~75% success rates in randomized trials 1

For Non-Critically Ill Patients

• Fluconazole is first-line for stable patients without recent azole exposure and low risk of resistant species 1, 2
• Dosing: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 1, 2
• This applies specifically to patients with mild-to-moderate illness who are hemodynamically stable 1

Species-Specific Considerations

• For C. parapsilosis: Fluconazole is preferred over echinocandins due to decreased echinocandin in vitro activity 1, 2
• For C. glabrata: Echinocandins are strongly preferred; if using azoles, high-dose fluconazole 800 mg daily or voriconazole only if susceptibility confirmed 1, 2
• For C. krusei: Use echinocandin or voriconazole (intrinsically fluconazole-resistant) 1, 2
• For C. auris: Echinocandins are mandatory first-line (90-98% susceptibility); fluconazole has only 10.7% susceptibility and is contraindicated 1, 3

Step-Down Therapy

• Transition from echinocandin to fluconazole after 5-7 days once clinically stable, isolate confirmed susceptible (e.g., C. albicans), and repeat blood cultures negative 1, 2

Critical Adjunctive Measures

• Remove central venous catheters as early as safely possible in non-neutropenic patients 1, 2
• Perform dilated ophthalmological examination within first week after diagnosis 1
• Continue treatment for 2 weeks after documented bloodstream clearance and symptom resolution 1, 2

Invasive Aspergillosis

Primary Therapy

• Voriconazole is the first-line agent with superior efficacy (52.8% response vs. 31.6% for conventional amphotericin B) 1, 4
• Dosing: 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily 1
• Alternative: Isavuconazole or posaconazole for patients intolerant to voriconazole 1

Second-Line Options

• Liposomal amphotericin B 5 mg/kg/day (or 10 mg/kg/day for CNS involvement) 1
• Amphotericin B deoxycholate and echinocandins may be considered as alternatives 1

Mucormycosis (COVID-Associated or Otherwise)

Primary Therapy

• Liposomal amphotericin B is first-line at 5 mg/kg/day without CNS involvement, or 10 mg/kg/day with CNS involvement 1
• Immediate surgical debridement is mandatory in addition to antifungal therapy 1
• Strict glycemic control and corticosteroid optimization required 1

Alternative Therapy

• Amphotericin B deoxycholate 1-1.5 mg/kg/day with slow infusion over 6-8 hours 1
• Posaconazole or isavuconazole as alternatives if amphotericin B contraindicated 1

Empirical Therapy in Febrile Neutropenia

• Liposomal amphotericin B or caspofungin are preferred over conventional amphotericin B due to better safety profiles 1
• Caspofungin shown as effective as and better tolerated than liposomal amphotericin B 1
• Azoles unsuitable if used for prior prophylaxis 1

Common Pitfalls to Avoid

• Never use fluconazole empirically in patients with recent azole exposure or suspected resistant species 1
• Do not delay treatment initiation: Early antifungal therapy profoundly impacts mortality; delayed therapy associated with higher mortality rates 1, 5
• Avoid echinocandin monotherapy for C. parapsilosis when fluconazole is an option 1, 2
• Never use fluconazole for C. auris (only 10.7% susceptibility) 1, 3
• Do not use conventional amphotericin B as first-line when safer alternatives available due to nephrotoxicity and infusion-related toxicity 1