What is the recommended treatment for patients with a high Candida score?

Treatment for Patients with High Candida Score

For critically ill patients with a high Candida score, initiate empirical antifungal therapy with an echinocandin (caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily) as first-line therapy, combined with immediate central venous catheter removal and source control. 1, 2

Understanding the Candida Score Context

The Candida score is a clinical prediction tool that incorporates risk factors for invasive candidiasis, but its utility has important limitations:

• In COVID-19 patients specifically, the Candida score may not reliably predict invasive candidiasis, as one study showed no difference in Candida scores between COVID-19 and non-COVID-19 patients with candidemia, despite significantly higher mortality in COVID-19 patients (87.5% vs 67.9%). 1
• The score should guide but not solely determine treatment decisions—clinical assessment of risk factors, serologic markers, and culture data from nonsterile sites must be integrated. 1

First-Line Empirical Treatment

For Critically Ill Patients or ICU Settings

Echinocandins are the preferred initial therapy with the following dosing regimens: 1, 2

• Caspofungin: 70 mg loading dose, then 50 mg daily
• Micafungin: 100 mg daily (standard dose for candidemia/invasive candidiasis) 3
• Anidulafungin: 200 mg loading dose, then 100 mg daily

Rationale for echinocandin preference: 1, 2

• Superior outcomes in critically ill patients
• Effective against fluconazole-resistant species (C. glabrata, C. krusei)
• Appropriate for patients with recent azole exposure

For Non-Critically Ill Patients

Fluconazole can be used if all of the following criteria are met: 1, 2

• Patient is hemodynamically stable (not critically ill)
• No recent azole exposure or prophylaxis
• Low risk of azole-resistant Candida species
• Dosing: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily

Do not use azoles for empirical therapy in patients who have received azole prophylaxis. 1

Essential Concurrent Interventions

Source Control (Critical)

Remove central venous catheters as early as possible when the catheter is presumed to be the source and can be safely removed. 1, 2

• This is a strong recommendation with moderate-quality evidence
• Catheter removal significantly improves outcomes
• For neutropenic patients, assess individually as other sources may predominate 2

For Intra-Abdominal Candidiasis

Surgical intervention with drainage and/or debridement is mandatory in addition to antifungal therapy. 1, 4

• Empirical antifungal therapy should be considered for patients with clinical evidence of intra-abdominal infection and significant risk factors including recent abdominal surgery, anastomotic leaks, or necrotizing pancreatitis 1
• Treatment choice follows the same principles as candidemia management 1

Duration of Therapy

Continue treatment for 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms attributable to candidemia. 1, 2, 5

• Perform follow-up blood cultures daily or every other day to establish when candidemia has cleared 1, 5
• For intra-abdominal candidiasis, duration is determined by adequacy of source control and clinical response 1

Transition to Step-Down Therapy

Transition from echinocandin to fluconazole after 5-7 days if: 1, 2

• Patient is clinically stable
• Isolates are susceptible to fluconazole (e.g., C. albicans)
• Repeat blood cultures are negative following initiation of therapy
• Fluconazole dosing for step-down: 400 mg (6 mg/kg) daily

For C. glabrata infections, transition to higher-dose fluconazole (800 mg daily) or voriconazole (200-300 mg twice daily) only if isolates are susceptible and patient has clinically improved. 1

Alternative Agents

Lipid Formulation Amphotericin B

Lipid formulation amphotericin B (3-5 mg/kg daily) is a reasonable alternative if: 1

• Intolerance to echinocandins or azoles
• Limited availability of other agents
• Suspected resistance to echinocandins and azoles

Amphotericin B deoxycholate is not recommended as initial therapy due to higher toxicity risk compared to lipid formulations. 1

Voriconazole

Voriconazole (400 mg twice daily for 2 doses, then 200 mg twice daily) is effective for candidemia but offers little advantage over fluconazole as initial therapy. 1

• Recommended as step-down oral therapy for selected cases of C. krusei candidemia 1

Monitoring Requirements

Ophthalmologic Examination

All non-neutropenic patients with candidemia must have a dilated ophthalmological examination, preferably by an ophthalmologist, within the first week after diagnosis. 1, 2, 5

Imaging Studies

For persistent candidemia, perform imaging of the genitourinary tract, liver, and spleen to detect metastatic complications. 1, 2

Common Pitfalls and Critical Warnings

Timing of Therapy

Delay in initiating appropriate antifungal therapy is associated with mortality approaching 100% in patients with septic shock due to Candida without adequate source control or antifungal therapy within 24 hours. 2

Species-Specific Considerations

For C. auris infections, echinocandins are strongly recommended due to extensive resistance to fluconazole (only 10.7% susceptibility) and amphotericin B (43.1% susceptibility). 1

Premature Treatment Changes

Avoid premature switching to fluconazole before confirming species identification and susceptibility, especially in critically ill patients. 3, 2

Do not discontinue therapy prematurely—failure to continue for at least 2 weeks after blood culture clearance leads to relapse. 3, 5

Prophylaxis Considerations

In ICUs with high rates of invasive candidiasis (>10%), fluconazole prophylaxis (400 mg daily) should be considered for high-risk patients. 1, 2

• For liver, pancreas, and small bowel transplant recipients at high risk: fluconazole 200-400 mg daily or liposomal amphotericin B 1-2 mg/kg daily for 7-14 days postoperatively 1