What is the recommended treatment for fungal infections?

Treatment of Fungal Infections

Primary Recommendation

For invasive candidiasis in critically ill or moderately severe patients, initiate treatment with an echinocandin (caspofungin, micafungin, or anidulafungin) as first-line therapy. 1 For less critically ill patients without recent azole exposure, fluconazole is an appropriate alternative. 1

Treatment Algorithm by Clinical Scenario

Invasive Candidiasis/Candidemia

Initial Therapy Selection:

• Critically ill or moderately severe patients: Echinocandin preferred 1

  • Caspofungin: 70 mg loading dose, then 50 mg daily 1
  • Micafungin: 100 mg daily 1
  • Anidulafungin: 200 mg loading dose, then 100 mg daily 1

• Less critically ill patients without recent azole exposure: Fluconazole 800 mg loading dose, then 400 mg daily 1

• Patients with recent azole exposure or high risk for resistant species: Echinocandin mandatory 1

Species-Specific Adjustments:

• C. albicans: Fluconazole appropriate if patient clinically stable; transition from echinocandin to fluconazole recommended once susceptibility confirmed 1

• C. glabrata: Echinocandin preferred; do not switch to azole without documented susceptibility 1

• C. parapsilosis: Fluconazole preferred over echinocandin 1

• C. krusei: Echinocandin, lipid formulation amphotericin B, or voriconazole (fluconazole ineffective) 1

Duration: Treat for 14 days after documented clearance from bloodstream and resolution of symptoms 1

Catheter Management: Remove intravenous catheters in non-neutropenic patients 1

Invasive Aspergillosis

Primary therapy: Voriconazole is the drug of choice 1, 2

• Loading: 6 mg/kg IV every 12 hours for 24 hours 1
• Maintenance: 4 mg/kg IV every 12 hours or 200 mg PO every 12 hours 1, 2

Alternative therapy: Lipid formulation amphotericin B 3-5 mg/kg daily 1

Duration: Continue until resolution or stabilization of all clinical and radiographic manifestations 1

Surgical intervention indicated for: Pulmonary lesions near great vessels, chest wall invasion, persistent hemoptysis from cavitary lesion 1

Site-Specific Candida Infections

Esophageal Candidiasis:

• Fluconazole 200-400 mg daily for 14-21 days until clinical improvement 1
• Alternative: Echinocandin or voriconazole 1

Oropharyngeal Candidiasis:

• Fluconazole 100-200 mg daily for 7-14 days 1
• Alternative: Itraconazole 200 mg daily or nystatin suspension 1

CNS Candidiasis:

• Amphotericin B deoxycholate with or without flucytosine 1
• Alternative: Fluconazole 400-800 mg daily for amphotericin-intolerant patients 1
• Remove intraventricular devices 1
• Treat until all symptoms, CSF abnormalities, and radiologic findings resolve 1

Candida Endophthalmitis:

• Amphotericin B 0.7-1 mg/kg with flucytosine 1
• Alternatives: Fluconazole, lipid amphotericin B, voriconazole, or echinocandin 1
• Diagnostic vitreal aspiration if etiology unknown 1
• Surgical intervention for severe endophthalmitis or vitritis 1
• Duration: At least 4-6 weeks with repeated examinations 1

Urinary Tract Infections:

• Asymptomatic cystitis: Usually no treatment needed unless high-risk surgical patient, neonate, or neutropenic 1
• Symptomatic cystitis: Fluconazole 200 mg daily for 14 days 1
• Pyelonephritis: Fluconazole 200-400 mg daily for 14 days 1

Neutropenic Patients

Empirical therapy for persistent fever:

• Amphotericin B deoxycholate 0.7-1.0 mg/kg daily 1
• Alternatives: Echinocandin, lipid amphotericin B, or voriconazole (if mold coverage desired) 1

Candidemia treatment: Continue for 2 weeks after first negative blood culture, symptom resolution, AND neutropenia resolution 1

Catheter removal: Controversial in neutropenic patients; individualize decision 1

Neonatal Candidiasis

Primary therapy: Amphotericin B deoxycholate 1.0 mg/kg daily 1

Alternatives: Fluconazole 12 mg/kg daily or echinocandin 1

Duration: 3 weeks for candidemia without persistent fungemia or metastatic complications 1

Mandatory evaluations: Lumbar puncture and dilated ophthalmoscopic examination for all neonates with positive sterile body fluid or urine cultures 1

Imaging: Genitourinary tract, liver, and spleen if sterile body fluid cultures persistently positive 1

Intra-Abdominal Fungal Infections

Severe community-acquired or healthcare-associated infections with Candida grown from cultures:

• C. albicans: Fluconazole appropriate 1

• Fluconazole-resistant species: Echinocandin (caspofungin, micafungin, or anidulafungin) 1

• Critically ill patients: Echinocandin preferred over triazole as initial therapy 1

Amphotericin B not recommended as initial therapy due to toxicity 1

Common Pitfalls and Caveats

Azole Resistance Considerations:

• Always favor echinocandins in patients with recent azole exposure 1
• C. glabrata has intrinsically reduced azole susceptibility; do not use fluconazole without documented susceptibility 1
• C. krusei is intrinsically fluconazole-resistant 1

Therapeutic Drug Monitoring:

• Consider voriconazole level monitoring due to variable pharmacokinetics 2
• Drug interactions common with azoles, particularly with anticonvulsants 1

Step-Down Therapy:

• Transition from echinocandin to fluconazole appropriate once patient clinically stable, cultures negative, and susceptibility confirmed 1
• Oral voriconazole achieves similar exposure to IV formulation due to high bioavailability 2

Pregnancy:

• Amphotericin B deoxycholate is treatment of choice in pregnant women 1

Antifungal Susceptibility Testing:

• Recommended for treatment failure or prior antifungal exposure 1
• Test all bloodstream and clinically relevant Candida isolates for azole susceptibility 1