What is the recommended treatment for a patient with fungal central line-associated bloodstream infection (CRBSI)?

Treatment of Fungal Central Line-Associated Bloodstream Infection (CRBSI)

Remove the catheter immediately and initiate systemic antifungal therapy—catheter retention in fungal CRBSI consistently worsens outcomes and increases mortality. 1, 2

Immediate Catheter Management

All catheters (short-term and long-term) must be removed in fungal CRBSI. 1, 2 The evidence is unequivocal:

• Short-term catheters: Remove immediately and send the catheter tip for culture 1
• Long-term catheters and implanted ports: Remove promptly, as all six prospective studies demonstrate that catheter retention worsens outcomes in candidemia 1, 2
• Timing: Catheter removal should occur within 72 hours, as retention beyond this point is associated with poorer outcomes 1

Exception for Extremely Limited Venous Access

For patients with no alternative access sites, exchange the catheter over a guidewire and perform catheter cultures as a temporary measure only 1. However, if the catheter tip grows the same Candida species as blood cultures, the catheter must be removed 1, 2.

Critical pitfall: Never delay catheter removal in an attempt to preserve venous access—all prospective studies show catheter retention worsens outcomes. 2

Systemic Antifungal Therapy

Empirical Therapy (Before Species Identification)

For septic patients or those with risk factors for candidemia, initiate an echinocandin empirically. 1 Risk factors include:

• Total parenteral nutrition 1
• Prolonged broad-spectrum antibiotics 1
• Hematologic malignancy 1
• Bone marrow or solid-organ transplant 1
• Femoral catheterization 1
• Colonization with Candida at multiple sites 1

Echinocandin dosing (first-line empirical therapy): 1, 3

• Caspofungin: 70 mg IV loading dose on Day 1, then 50 mg IV daily 3
• Micafungin: 100 mg IV daily 1
• Anidulafungin: 200 mg IV loading dose, then 100 mg IV daily 1

Fluconazole can be used empirically only if: 1

• No azole exposure in the previous 3 months 1
• Healthcare setting has very low risk of C. krusei or C. glabrata infection 1

Targeted Therapy (After Species Identification)

For Azole-Susceptible Species (C. albicans, susceptible C. parapsilosis)

Fluconazole 400 mg IV daily (6 mg/kg for pediatrics) for 14 days after the first negative blood culture 1, 4, 2, 5

• Fluconazole is equivalent to amphotericin B for azole-susceptible strains 1
• Can transition from echinocandin to fluconazole after 5-7 days if patient is clinically stable, follow-up cultures are negative, and isolate is susceptible 5

For Azole-Resistant or Reduced-Susceptibility Species (C. krusei, C. glabrata)

Continue echinocandin or use lipid formulation of amphotericin B: 1, 2

• Echinocandins (preferred): Continue dosing as above 1, 2
• Lipid formulations of amphotericin B: 3-5 mg/kg IV daily 1, 2

Critical pitfall: Never use fluconazole empirically before species identification and susceptibility testing, as C. krusei has intrinsic resistance and C. glabrata frequently has reduced susceptibility. 2

Duration of Therapy

Standard duration: 14 days after the first negative blood culture result and resolution of symptoms 1, 4, 2, 5

Extended Duration (4-6 weeks) Required For:

• Persistent fungemia >72 hours after catheter removal and appropriate therapy 1, 5
• Suppurative thrombophlebitis 1
• Endocarditis 1, 5
• Metastatic complications (endophthalmitis, osteomyelitis) 5

Critical pitfall: Never stop therapy before 14 days after documented clearance, as premature discontinuation increases relapse risk. 2

Monitoring and Follow-Up

Obtain follow-up blood cultures daily or every other day until clearance is documented 2, 5

• Day 1 for counting treatment duration begins with the first negative blood culture 5
• If blood cultures remain positive at 72 hours despite appropriate therapy, evaluate for complications: 2
  • Endocarditis (especially with prosthetic valves or prolonged candidemia) 2
  • Suppurative thrombophlebitis (confirm with CT or ultrasound) 1, 2
  • Endophthalmitis 2
  • Metastatic infection 2

Pediatric Considerations (3 months to 17 years)

Dosing based on body surface area (BSA): 3

• Loading dose: 70 mg/m² IV on Day 1 (maximum 70 mg) 3
• Maintenance dose: 50 mg/m² IV daily (maximum 70 mg) 3
• If inadequate response, increase to 70 mg/m² daily (not to exceed 70 mg) 3

Fungal infections in children require significantly longer time to clear without catheter removal, and mortality is higher when catheters are retained. 2

What NOT to Do

Antibiotic lock therapy is NOT recommended for fungal CRBSI 1, 2

• Antifungal lock therapy remains investigational with insufficient evidence for routine use 1, 2
• Limited data on amphotericin B lock therapy exists, but this approach lacks evidence for standard practice 2

Never assume symptom resolution after catheter removal means cure—systemic antifungal therapy is mandatory even if clinical manifestations resolve 1, 4, 2

Impact of Delayed Treatment

Delaying antifungal treatment >12 hours after drawing the first positive blood culture is independently associated with increased hospital mortality (adjusted odds ratio 2.09). 6 This underscores the importance of early empirical therapy in high-risk patients and prompt initiation of targeted therapy once fungal infection is identified.