What is the appropriate treatment for a patient with a Candida infection?

Treatment of Candida Infection

For invasive candidiasis and candidemia, echinocandins (caspofungin, micafungin, or anidulafungin) are the preferred first-line agents for critically ill patients, while fluconazole remains appropriate for hemodynamically stable patients without recent azole exposure and with susceptible Candida species. 1, 2, 3

Initial Assessment: Infection vs. Colonization

Before initiating antifungal therapy, distinguish true infection from colonization:

• Respiratory secretions: Candida isolated from sputum or BAL almost always represents colonization and should NOT be treated, even in intubated ICU patients—autopsy studies show none of 77 ICU patients with positive respiratory cultures had actual Candida pneumonia 2
• Asymptomatic candiduria: Does not require treatment in males unless neutropenic or undergoing urologic procedures 2
• Stool specimens: Yeast in feces represents colonization and should NOT be treated unless accompanied by clinical signs of intra-abdominal infection with specific risk factors (recent abdominal surgery with anastomotic leaks, recurrent perforations, necrotizing pancreatitis) 4

Treatment by Site of Infection

Candidemia and Invasive Candidiasis

Initial therapy selection:

• Critically ill patients or recent azole exposure: Echinocandins are preferred 1, 2, 3

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

• Hemodynamically stable patients without recent azole exposure: Fluconazole 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 1, 3

• Alternative agents: Liposomal amphotericin B 3-5 mg/kg daily or amphotericin B deoxycholate 0.5-1 mg/kg daily if intolerance or limited availability of other antifungals 1

Species-specific considerations:

• C. glabrata: Echinocandin strongly preferred due to reduced azole susceptibility 1, 2, 3
• C. parapsilosis: Fluconazole or liposomal amphotericin B preferred (echinocandins have reduced activity) 1, 2
• C. krusei: Echinocandin, liposomal amphotericin B, or voriconazole (inherent fluconazole resistance) 1, 2, 3
• C. albicans: Fluconazole appropriate for susceptible isolates in stable patients 1, 2

Critical management steps:

• Start antifungal therapy within 24 hours of positive blood culture 1, 2, 3
• Remove all central venous catheters if feasible, particularly in non-neutropenic patients 1, 2, 3
• Obtain daily or every-other-day blood cultures until clearance documented 1
• Perform dilated ophthalmological examination to exclude endophthalmitis (after neutrophil recovery in neutropenic patients) 1

Duration: Continue therapy for 2 weeks after documented bloodstream clearance AND resolution of symptoms 1, 2, 3

Step-down therapy: Transition from amphotericin B or echinocandin to fluconazole 400 mg daily is appropriate for clinically stable patients with susceptible isolates (e.g., C. albicans) 1

Intra-Abdominal Candidiasis

• Source control is mandatory: Adequate drainage and/or debridement is more important than antifungal selection—mortality exceeds 60% without proper source control 2, 4
• Empiric therapy indications: Clinical evidence of intra-abdominal infection PLUS significant risk factors (recent abdominal surgery, anastomotic leaks, necrotizing pancreatitis) 2, 4
• Antifungal selection: Same algorithm as candidemia—echinocandins for severe cases, fluconazole for susceptible species in stable patients 2, 4
• Duration: 2-3 weeks based on clinical response and adequacy of source control 2, 4

Oropharyngeal and Esophageal Candidiasis

Oropharyngeal candidiasis:

• Mild disease: Clotrimazole troches 10 mg five times daily for 7-14 days 3
• Moderate to severe: Fluconazole 200 mg loading dose, then 100 mg daily for at least 2 weeks 2, 3

Esophageal candidiasis:

• First-line: Fluconazole 200 mg loading dose, then 100-200 mg daily (up to 400 mg based on severity) 2, 3, 5
• Duration: Minimum 3 weeks AND at least 2 weeks after symptom resolution 2

Urinary Tract Candidiasis

• Asymptomatic candiduria: Remove or replace urinary catheters; treatment rarely required 2, 3
• Symptomatic cystitis: Fluconazole 200 mg daily for 7-14 days for susceptible organisms 2, 3
• Pyelonephritis: Fluconazole 200-400 mg daily for 2 weeks 2, 3

Vulvovaginal Candidiasis

• Uncomplicated: Fluconazole 150 mg PO single dose, or topical azoles intravaginally for 1-7 days 2
• Recurrent: Fluconazole 150 mg single dose, followed by maintenance therapy with fluconazole 150 mg weekly for 6 months 2

Endocarditis

• Initial therapy: Liposomal amphotericin B 3-5 mg/kg daily ± flucytosine 25 mg/kg four times daily, or high-dose echinocandin 2
• Valve replacement strongly recommended 2
• Duration: At least 6 weeks after surgery (longer if perivalvular abscess present) 2

CNS Infections (Meningitis)

• Initial therapy: Amphotericin B deoxycholate 1 mg/kg IV daily, or liposomal amphotericin B 5 mg/kg daily, with consideration of adding flucytosine 25 mg/kg four times daily 2, 3
• Step-down: Fluconazole 12 mg/kg daily (800 mg) for susceptible isolates 2
• Duration: Continue until all signs, symptoms, CSF abnormalities, and radiological findings resolve 2

Osteomyelitis and Arthritis

• Surgical debridement required first 1
• Initial therapy: Amphotericin B 0.5-1 mg/kg daily for 2-3 weeks 1
• Step-down: Fluconazole 6 mg/kg daily for susceptible isolates 1
• Total duration: 6-12 months 1
• Arthritis management: Adequate/repeated drainage critical; hip arthritis requires open drainage 1

Special Populations

Neutropenic Patients

Candidemia:

• Echinocandin, liposomal amphotericin B 3-5 mg/kg daily, or fluconazole 800 mg loading then 400 mg daily (only if no recent azole exposure and not critically ill) 1, 3
• Duration: 2 weeks after bloodstream clearance, symptom resolution, AND neutropenia resolution 1
• Consider catheter removal (controversial in this population) 1

Empiric therapy for persistent fever:

• Liposomal amphotericin B 3-5 mg/kg daily, caspofungin 70 mg loading then 50 mg daily, or voriconazole 400 mg (6 mg/kg) IV twice daily for 2 doses then 200 mg (3 mg/kg) twice daily 1, 2
• Initiate after 4-6 days of persistent fever despite antibacterial therapy 1, 2
• Continue until neutropenia resolution 2
• Do NOT use azoles in patients on prior azole prophylaxis 1

Neonates

• First-line: Amphotericin B deoxycholate 1 mg/kg IV daily 3
• Alternative: Fluconazole 12 mg/kg IV or oral daily (not in patients on fluconazole prophylaxis) 3
• Prophylaxis: High-risk neonates in nurseries with >10% invasive candidiasis rates should receive fluconazole 3-6 mg/kg twice weekly 2

Critical Pitfalls to Avoid

• Do NOT delay therapy: Mortality increases significantly when antifungal therapy is delayed beyond 24 hours of positive blood culture 1, 2, 3, 6
• Do NOT use fluconazole empirically in critically ill patients: Without knowing susceptibility patterns, C. glabrata resistance is common 1, 2, 4
• Do NOT treat colonization: Respiratory secretions, asymptomatic candiduria, and stool yeast represent colonization, not infection 2, 4
• Do NOT forget catheter removal: Failure to remove central lines in non-neutropenic patients increases mortality 1, 2
• Do NOT stop therapy prematurely: Complete full treatment course after bloodstream clearance to prevent relapse 2, 3
• Avoid fluconazole with clopidogrel: Significant drug interaction reduces antiplatelet efficacy by 25-30% 3
• Do NOT delay source control in intra-abdominal infections: Inadequate drainage results in treatment failure regardless of appropriate antifungal therapy 2, 4

Dose Adjustments

If inadequate response on fluconazole:

• Increase from 200 mg every 12 hours to 300 mg every 12 hours (or 100 mg to 150 mg for patients <40 kg) 1

If intolerance:

• Reduce oral dose by 50 mg steps to minimum 200 mg every 12 hours 1
• Reduce IV dose from 4 mg/kg to 3 mg/kg every 12 hours 1

Hepatic impairment: Decrease maintenance dose 1

Drug interactions: Increase dose when co-administered with phenytoin or efavirenz 1