What is the management of Candida infection in critical care settings?

Management of Candida Infection in Critical Care Settings

In critically ill patients with suspected invasive candidiasis, an echinocandin (caspofungin: loading dose of 70 mg, then 50 mg daily; micafungin: 100 mg daily; or anidulafungin: loading dose of 200 mg, then 100 mg daily) is the preferred empiric therapy and should be started immediately in patients with risk factors and signs of septic shock. 1

Risk Assessment and Diagnosis

• Empiric antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever 1
• Risk factors include Candida colonization, severity of illness, exposure to broad-spectrum antibiotics, recent major surgery (particularly abdominal), necrotizing pancreatitis, dialysis, parenteral nutrition, corticosteroids, and central venous catheters 1
• Assessment should include clinical risk factors, surrogate markers for invasive candidiasis, and/or culture data from nonsterile sites 1
• Daily bathing of ICU patients with chlorhexidine can decrease the incidence of bloodstream infections including candidemia 1

First-Line Treatment Options

For Suspected Candidiasis (Empiric Therapy):

• Preferred therapy: Echinocandin (strong recommendation; moderate-quality evidence) 1

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

• Alternative therapy: Fluconazole, 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, for patients with no recent azole exposure and not colonized with azole-resistant Candida species 1

• Second alternative: Lipid formulation AmB, 3-5 mg/kg daily, if intolerant to other antifungal agents 1

For Documented Candida Infections:

• For C. krusei infections: an echinocandin, lipid formulation AmB, or voriconazole is recommended 1
• For chronic disseminated (hepatosplenic) candidiasis: initial therapy with lipid formulation AmB or an echinocandin for several weeks, followed by oral fluconazole 400 mg daily 1

Duration of Therapy

• For candidemia without metastatic complications: minimum 2 weeks after documented clearance of Candida from the bloodstream, provided neutropenia and symptoms have resolved 1
• For empiric therapy in patients who improve: 2 weeks, the same as for documented candidemia 1
• For chronic disseminated candidiasis: continue until lesions resolve on repeat imaging, which is usually several months 1
• Consider stopping antifungal therapy if no clinical response at 4-5 days and no subsequent evidence of invasive candidiasis or negative non-culture-based diagnostic assay with high negative predictive value 1

Special Considerations

Central Venous Catheter Management:

• In non-neutropenic patients, CVC removal is strongly recommended 1
• In neutropenic patients, catheter removal should be considered on an individual basis as sources other than CVC (e.g., gastrointestinal tract) predominate 1

For Neutropenic Patients:

• G-CSF-mobilized granulocyte transfusions can be considered in cases of persistent candidemia with anticipated protracted neutropenia 1
• Ophthalmological examinations should be performed within the first week after recovery from neutropenia 1

For Patients with Chronic Disseminated Candidiasis:

• If chemotherapy or hematopoietic cell transplantation is required, it should not be delayed, and antifungal therapy should be continued throughout the period of high risk 1
• For debilitating persistent fevers, short-term (1-2 weeks) treatment with NSAIDs or corticosteroids can be considered 1

Monitoring and Follow-up

• For candidemia: perform dilated funduscopic examinations to rule out endophthalmitis 1
• For persistent candidemia: consider imaging of the genitourinary tract, liver, and spleen 1
• Monitor for clinical response and clearance of Candida from the bloodstream 1

Common Pitfalls and Caveats

• Delay in initiating appropriate antifungal therapy is associated with increased mortality; in patients with septic shock due to Candida without adequate source control or antifungal therapy within 24 hours, mortality approaches 100% 1
• Empiric therapy based solely on colonization with Candida species is inadequate 1
• In ICUs with high rates (>5%) of invasive candidiasis, fluconazole prophylaxis could be considered for high-risk patients 1
• Micafungin has demonstrated efficacy comparable to caspofungin in treating candidemia and other Candida infections, with 70.7% treatment success at the end of IV therapy 2
• The number needed to treat with empiric antifungal therapy for one patient with Candida-related septic shock to receive appropriate treatment is approximately 20 patients 3