What is the recommended treatment for a patient with candidiasis, considering the severity of the infection and the patient's immune status?

Treatment of Candidiasis

The treatment of candidiasis depends critically on the anatomic site of infection and immune status: fluconazole 200-400 mg daily for 14-21 days is first-line for esophageal candidiasis, while candidemia requires either an echinocandin (preferred for critically ill/neutropenic patients) or fluconazole 800 mg loading dose then 400 mg daily for non-neutropenic patients, continuing for 2 weeks after bloodstream clearance. 1, 2

Oropharyngeal and Esophageal Candidiasis

Oropharyngeal Disease

• Topical clotrimazole troches 10 mg five times daily for 7-14 days is appropriate for mild disease 3
• Oral fluconazole 100-200 mg daily for 7-14 days for moderate to severe disease 3

Esophageal Disease

• Fluconazole 200-400 mg daily (oral or IV) for 14-21 days is the recommended first-line therapy 1
• For patients unable to tolerate oral therapy, use IV fluconazole 400 mg daily OR an echinocandin (micafungin 150 mg daily, caspofungin 70 mg loading then 50 mg daily, or anidulafungin 200 mg daily) 1
• De-escalate to oral fluconazole once the patient tolerates oral intake 1

Fluconazole-Refractory Esophageal Disease

• Itraconazole solution 200 mg daily OR voriconazole 200 mg twice daily (IV or oral) for 14-21 days 1
• Alternative options include echinocandins for 14-21 days OR amphotericin B deoxycholate 0.3-0.7 mg/kg daily for 21 days 1
• Posaconazole suspension 400 mg twice daily or extended-release tablets 300 mg once daily may be considered but is a weaker recommendation 1

Candidemia and Invasive Candidiasis

Non-Neutropenic Patients

• Fluconazole 800 mg (12 mg/kg) loading dose on day 1, then 400 mg (6 mg/kg) daily is appropriate for stable, non-critically ill patients without prior azole exposure 2
• Echinocandins are preferred for critically ill patients or those with recent azole exposure 2
• Remove central venous catheters as early as possible when presumed to be the infection source 1, 2
• Continue treatment for 2 weeks after documented bloodstream clearance and symptom resolution 1, 2

Neutropenic Patients

• Echinocandins are first-line therapy, but fluconazole 800 mg loading then 400 mg daily is an alternative for non-critically ill patients without prior azole exposure 2
• Step-down to fluconazole 400 mg daily can be used during persistent neutropenia in clinically stable patients with susceptible isolates after bloodstream clearance 2

Critical Monitoring Requirements

• Perform follow-up blood cultures daily or every other day to establish when candidemia has cleared 2
• All non-neutropenic patients require dilated ophthalmological examination within the first week after diagnosis to rule out endophthalmitis 1, 2
• CT or ultrasound imaging of genitourinary tract, liver, and spleen if blood cultures remain persistently positive 1

Intra-Abdominal Candidiasis

• Empiric antifungal therapy is indicated for patients with clinical evidence of intra-abdominal infection and significant risk factors (recent abdominal surgery, anastomotic leaks, necrotizing pancreatitis) 1
• Source control with appropriate drainage and/or debridement is mandatory 1
• Antifungal choice follows the same principles as candidemia treatment (echinocandins for critically ill, fluconazole for stable patients) 1
• Duration depends on adequacy of source control and clinical response 1

Central Nervous System Candidiasis

• Amphotericin B deoxycholate 1 mg/kg IV daily is the recommended initial treatment 1
• Liposomal amphotericin B 5 mg/kg daily is an alternative 1
• Flucytosine 25 mg/kg four times daily may be added as salvage therapy for patients not responding to initial amphotericin B, though adverse effects are frequent 1
• Step-down to fluconazole 12 mg/kg daily after initial response for susceptible isolates 1
• Continue therapy until all signs, symptoms, CSF abnormalities, and radiological findings resolve 1
• Remove infected CNS devices (ventriculostomy drains, shunts) if possible 1

Candida Endocarditis

• Lipid formulation amphotericin B 3-5 mg/kg daily with or without flucytosine 25 mg/kg four times daily OR high-dose echinocandin (caspofungin 150 mg daily, micafungin 150 mg daily, or anidulafungin 200 mg daily) for initial therapy 1
• Step-down to fluconazole 400-800 mg daily for patients with susceptible isolates who demonstrate clinical stability and bloodstream clearance 1

Neonatal Candidiasis

• Amphotericin B deoxycholate 1 mg/kg IV daily is first-line 1
• Lipid formulation amphotericin B 3-5 mg/kg daily should be used with caution, particularly with urinary tract involvement 1
• Echinocandins should be limited to salvage therapy or situations where resistance/toxicity preclude amphotericin B or fluconazole 1
• Lumbar puncture and dilated retinal examination are mandatory in neonates with positive blood/urine cultures 1
• Continue treatment for 2 weeks after bloodstream clearance and symptom resolution 1

Special Populations and Considerations

Recurrent Infections

• Chronic suppressive therapy with fluconazole 100-200 mg three times weekly is recommended for patients with recurrent esophageal candidiasis 1
• Antiretroviral therapy is strongly recommended for HIV-infected patients to reduce recurrence 1

Respiratory Candida Isolation

• Growth of Candida from respiratory secretions usually indicates colonization and rarely requires antifungal treatment 1

Critical Pitfalls to Avoid

• Never use fluconazole empirically in patients who received azole prophylaxis—use an echinocandin instead for suspected fluconazole-resistant species 3
• Avoid concomitant fluconazole and clopidogrel due to significant drug interaction reducing antiplatelet efficacy by 25-30% 3
• Premature discontinuation leads to relapse—always complete the full treatment course after bloodstream clearance 2
• Positive Candida cultures from skin/mucosa do not always indicate infection since these are normal inhabitants; correlate with clinical findings 4