What is the best antifungal for empirical therapy in sepsis?

Echinocandins Are the Preferred Antifungal for Empirical Therapy in Sepsis

For empirical antifungal therapy in sepsis, echinocandins (anidulafungin, micafungin, or caspofungin) are the preferred first-line agents, especially in hemodynamically unstable patients with septic shock or those with recent azole exposure. 1, 2

Risk Assessment for Fungal Infection in Sepsis

• Empiric antifungal therapy should be considered in critically ill septic patients with risk factors for invasive candidiasis when no other cause of fever is identified 2
• Key risk factors for invasive Candida infections include:
  • Immunocompromised status (neutropenia, chemotherapy, transplant, diabetes mellitus) 1
  • Prolonged invasive vascular devices (hemodialysis catheters, central venous catheters) 1
  • Total parenteral nutrition 1, 2
  • Necrotizing pancreatitis 1
  • Recent major surgery (particularly abdominal) 1
  • Prolonged administration of broad-spectrum antibiotics 1
  • Prolonged hospital/ICU admission 1
  • Recent fungal infection 1
  • Multisite Candida colonization 1, 3

First-Line Antifungal Selection

• Echinocandins are the preferred empiric therapy for suspected invasive candidiasis in sepsis, particularly in:

  • Patients with septic shock 1, 2
  • Patients with recent azole exposure 1, 2
  • When Candida glabrata or Candida krusei infection is suspected 1

• Recommended echinocandin dosing regimens:

  • Anidulafungin: 200 mg loading dose, then 100 mg daily 2
  • Micafungin: 100 mg daily 2
  • Caspofungin: 70 mg loading dose, then 50 mg daily 2

Alternative Antifungal Options

• Fluconazole (800 mg loading dose, then 400 mg daily) is an acceptable alternative in:

  • Hemodynamically stable, less ill patients 1
  • Patients without previous triazole exposure 1
  • Patients not known to be colonized with azole-resistant species 1, 2

• Liposomal formulations of amphotericin B (3-5 mg/kg daily) are reasonable alternatives in patients with echinocandin intolerance or toxicity 1, 4

Timing and Duration of Therapy

• Antifungal therapy should be initiated as soon as possible in patients with suspected fungal sepsis, ideally within 1 hour of recognition 1
• Delayed antifungal therapy is associated with increased mortality in patients with septic shock due to Candida 2, 5
• Empiric antifungal therapy should typically be continued for 14 days in patients who improve clinically 2
• De-escalation to a more targeted antifungal should occur once the pathogen and susceptibilities are identified 1

Special Considerations

• Central venous catheter removal is strongly recommended in non-neutropenic patients with candidemia 2
• For neutropenic patients, catheter removal should be considered on an individual basis 2
• Dilated funduscopic examinations should be performed to rule out endophthalmitis in patients with candidemia 2
• For persistent candidemia, consider imaging of the genitourinary tract, liver, and spleen 2

Common Pitfalls to Avoid

• Delaying antifungal therapy in high-risk patients with septic shock can significantly increase mortality 2, 6
• Empiric therapy based solely on colonization with Candida species without other risk factors is inadequate 2
• Premature discontinuation of antifungal therapy before complete resolution can lead to relapse, especially in immunocompromised patients 4
• Failure to consider local resistance patterns when selecting empiric therapy 1

Evidence on Outcomes

• Early appropriate antifungal therapy significantly reduces time to appropriate treatment in Candida-related septic shock (10.6 hours vs 40.5 hours with standard therapy) 7
• Patients receiving empiric therapy are more likely to receive appropriate therapy within 12 hours of shock onset (69.2% vs 6.7%) 7
• The EMPIRICUS trial showed that empirical micafungin decreased the rate of new invasive fungal infections compared to placebo (3% vs 12%) in critically ill patients with Candida colonization and sepsis 3