How should candidemia be treated regarding timing of therapy duration, source control, and antifungal selection?

Management of Candidemia

For candidemia, initiate an echinocandin (caspofungin 70 mg loading then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading then 100 mg daily) as first-line therapy for most patients, remove central venous catheters within 24-48 hours when feasible, obtain daily blood cultures until clearance, perform dilated fundoscopy within one week, and treat for 14 days after the first negative blood culture plus complete symptom resolution. 1

Initial Antifungal Selection

Non-Neutropenic Patients

Echinocandins are preferred for most patients, particularly those with moderate-to-severe illness, recent azole exposure, or risk factors for fluconazole-resistant species (C. glabrata, C. krusei). 1

• Caspofungin: 70 mg loading dose, then 50 mg daily 1
• Micafungin: 100 mg daily (no loading dose required) 1, 2
• Anidulafungin: 200 mg loading dose, then 100 mg daily 1

Fluconazole is acceptable (800 mg loading, then 400 mg daily) only for patients who are not critically ill, have no recent azole exposure, and when fluconazole-susceptible species are likely. 1

Lipid formulation amphotericin B (3-5 mg/kg daily) serves as an alternative when echinocandins or azoles cannot be used due to resistance, intolerance, or limited availability. 1

Neutropenic Patients

Echinocandins remain first-line with the same dosing as non-neutropenic patients. 1

• Fluconazole (800 mg loading, then 400 mg daily) is acceptable only for non-critically ill patients without prior azole exposure. 1
• Voriconazole (400 mg twice daily for 2 doses, then 200-300 mg twice daily) can be considered when additional mold coverage is desired. 1

Species-Specific Considerations

C. albicans

Transition to fluconazole (400 mg daily) after 5-7 days once clinically stable with negative repeat blood cultures and confirmed susceptibility. 1

C. glabrata

Echinocandins are strongly preferred. 1 Transition to fluconazole (800 mg daily) or voriconazole only after confirming susceptibility; do not assume susceptibility. 1

C. parapsilosis

Fluconazole or lipid amphotericin B are preferred over echinocandins due to higher MICs with echinocandins, though continuing an echinocandin is reasonable if the patient is stable with negative follow-up cultures. 1

C. krusei

Use an echinocandin, lipid amphotericin B, or voriconazole; fluconazole is intrinsically resistant. 1

Multidrug-Resistant Isolates

For suspected azole- and echinocandin-resistant infections, use lipid formulation amphotericin B (3-5 mg/kg daily). 1

Source Control: Central Venous Catheter Management

Remove all central venous catheters as early as safely possible in non-neutropenic patients—ideally within 24-48 hours of candidemia diagnosis. 1, 2 This is a strong recommendation with moderate-quality evidence and significantly impacts mortality. 1

For neutropenic patients, catheter removal should be considered but remains controversial; the decision depends on individual patient factors including alternative vascular access and bleeding risk. 1

Monitoring and Follow-Up

Blood Culture Surveillance

Obtain follow-up blood cultures daily or every other day until clearance is documented. 1 The 14-day treatment duration begins only after the first negative culture, not from therapy initiation. 1, 2

Ophthalmologic Examination

All non-neutropenic patients require dilated fundoscopy within the first week after diagnosis, preferably by an ophthalmologist. 1 Approximately 16% of candidemia patients have ocular involvement, and undetected endophthalmitis mandates 4-6 weeks of therapy rather than 14 days. 3, 2

For neutropenic patients, defer the examination until after neutrophil recovery (ANC >500 cells/μL), as findings may be minimal during neutropenia. 2

Imaging for Metastatic Complications

Consider imaging of the genitourinary tract, liver, and spleen if fever persists beyond 72 hours of appropriate therapy or if focal symptoms develop. 3, 2 Metastatic complications require prolonged treatment lasting months. 2

Duration of Therapy

Standard Duration

Treat for a minimum of 14 days after documented clearance of Candida from the bloodstream AND complete resolution of all symptoms attributable to candidemia. 1, 2 This is a strong recommendation with moderate-quality evidence. 1

The 14-day clock starts only after both negative blood cultures and symptom resolution (fever, hemodynamic instability, leukocytosis) are confirmed. 3, 2

Neutropenic Patients

Continue therapy for 14 days after bloodstream clearance, symptom resolution, AND resolution of neutropenia (ANC >500 cells/μL). 1, 2 Treatment may extend beyond 14 days if neutropenia persists. 2

Neonates

Provide a minimum of 3 weeks of therapy from the point of clinical improvement due to higher risk of disseminated disease. 3, 2 Perform lumbar puncture and dilated ophthalmologic examination in all neonates with positive Candida blood or urine cultures. 2

When Blood Cultures Are Unavailable

Treat for at least 14 days from when the patient becomes clinically stable and completely asymptomatic, using clinical parameters (resolution of fever, hemodynamic stability, normalized white cell count, absence of organ-specific symptoms) to define stability. 3, 2

Metastatic Complications

Ocular involvement requires 4-6 weeks of therapy. 2 Other metastatic complications (endocarditis, osteomyelitis, CNS involvement) require prolonged treatment lasting months. 2

Susceptibility Testing

Test all bloodstream and clinically relevant Candida isolates for azole susceptibility. 1 Consider echinocandin susceptibility testing for patients with prior echinocandin exposure or infections with C. glabrata or C. parapsilosis. 1

Common Pitfalls to Avoid

• Do not discontinue therapy at 7-10 days based solely on clinical improvement—complete the full 14-day course after documented clearance and symptom resolution. 3, 2, 4
• Do not count the 14-day minimum from therapy initiation—it begins only after negative cultures and symptom resolution. 2
• Do not skip the ophthalmologic examination—detection of endophthalmitis mandates 4-6 weeks of therapy instead of 14 days. 3, 2
• Do not assume clinical improvement equals bloodstream clearance—obtain follow-up blood cultures to confirm eradication. 2
• Do not delay antifungal therapy—early treatment (within 48 hours) significantly improves survival compared to delayed therapy. 4, 5
• Do not transition to fluconazole for C. glabrata without confirmed susceptibility—resistance is common and assuming susceptibility increases mortality. 1