What is the recommended treatment approach for a patient with candidiasis, considering factors such as severity, location, and underlying medical conditions, including diabetes and immunosuppression?

Treatment of Candidiasis: 2016 IDSA Guidelines Summary

The 2016 IDSA guidelines represent the most current comprehensive approach to candidiasis management, emphasizing early antifungal initiation, source control, and risk-stratified therapy selection based on illness severity and prior azole exposure. 1

General Principles

Timing and Monitoring

• Antifungal therapy must be initiated within 24 hours of a positive blood culture for yeast, as delays are associated with increased mortality 1
• Follow-up blood cultures should be performed daily or every other day until clearance is documented 1
• All patients with candidemia require dilated ophthalmological examination to exclude endophthalmitis, performed after neutrophil recovery in neutropenic patients 1
• Treatment duration is 14 days after documented bloodstream clearance and resolution of symptoms for uncomplicated candidemia 1

Candidemia in Non-Neutropenic Adults

First-Line Therapy Selection

For moderately severe to severe illness or recent azole exposure, echinocandins are the preferred initial therapy 1, 2, 3:

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

For stable, non-critically ill patients without recent azole exposure, fluconazole is appropriate 1, 2, 3:

• Loading dose: 800 mg (12 mg/kg), then 400 mg (6 mg/kg) daily 1

Alternative Options

• Lipid formulation amphotericin B: 3-5 mg/kg daily 1
• Amphotericin B deoxycholate: 0.5-1 mg/kg daily 1
• Voriconazole: 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily 1, 4

Critical Management Steps

• Remove all intravascular catheters if possible, as this is strongly recommended 1, 3
• Step-down to oral fluconazole is appropriate once the patient is clinically stable and isolates are susceptible 1, 3

Candidemia in Neutropenic Patients

Primary Therapy

Fluconazole is recommended for patients without recent azole exposure who are not critically ill 1:

• Loading dose: 800 mg (12 mg/kg), then 400 mg (6 mg/kg) daily 1

Echinocandins or lipid formulation amphotericin B (3-5 mg/kg daily) are preferred for critically ill patients 1

Alternative Therapy

• Voriconazole 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily when additional mold coverage is desired 1
• Catheter removal is advised but remains controversial in this population 1

Neonatal Candidiasis

First-Line Treatment

Amphotericin B deoxycholate 1 mg/kg IV daily is the recommended first-line therapy 1, 3

Alternative Options

• Fluconazole 12 mg/kg IV or oral daily is reasonable for patients not on fluconazole prophylaxis 1
• Lipid formulation amphotericin B 3-5 mg/kg daily (use with caution in urinary tract involvement) 1
• Echinocandins should be limited to salvage therapy or when resistance/toxicity precludes other agents 1

Mandatory Evaluations

• Lumbar puncture and dilated retinal examination for all neonates with positive blood/urine cultures 1, 3
• CT or ultrasound imaging of genitourinary tract, liver, and spleen if blood cultures remain persistently positive 1
• Central venous catheter removal is strongly recommended 1
• Treatment duration: 2 weeks after documented clearance and symptom resolution 1

CNS Candidiasis

Initial Therapy

Amphotericin B deoxycholate 1 mg/kg IV daily is recommended for initial treatment 1, 3

Alternative Initial Therapy

• Liposomal amphotericin B 5 mg/kg daily 1, 3
• Addition of flucytosine 25 mg/kg four times daily may be considered as salvage therapy, though adverse effects are frequent 1

Step-Down Therapy

• Fluconazole 400-800 mg (6-12 mg/kg) daily after response to initial treatment for susceptible isolates 1, 3
• Therapy continues until all signs, symptoms, CSF and radiological abnormalities resolve 1
• Infected CNS devices (ventriculostomy drains, shunts) must be removed if possible 1, 3

Urinary Tract Candidiasis

Asymptomatic Candiduria

Treatment is NOT recommended unless the patient is high-risk (neutropenic, very low birth weight infants <1500g, or undergoing urologic procedures) 1, 3

• Elimination of predisposing factors (indwelling catheters) is strongly recommended 1
• High-risk patients should be treated as for candidemia 1, 3
• Patients undergoing urologic procedures: fluconazole 400 mg (6 mg/kg) daily OR amphotericin B deoxycholate 0.3-0.6 mg/kg daily for several days before and after the procedure 1, 3

Symptomatic Cystitis

For fluconazole-susceptible organisms: oral fluconazole 200 mg (3 mg/kg) daily for 2 weeks 1, 3

For fluconazole-resistant organisms:

• C. glabrata: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days OR oral flucytosine 25 mg/kg four times daily for 7-10 days 1
• C. krusei: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days 1
• Removal of indwelling bladder catheter is strongly recommended 1
• Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) may be useful for fluconazole-resistant species 1

Pyelonephritis

For fluconazole-susceptible organisms: fluconazole 200-400 mg (3-6 mg/kg) daily for 2 weeks 1, 3

For fluconazole-resistant organisms:

• Amphotericin B deoxycholate 0.3-0.6 mg/kg daily with or without flucytosine 25 mg/kg four times daily for 2 weeks 1
• Flucytosine monotherapy 25 mg/kg four times daily for 2 weeks could be considered 1

Intra-Abdominal Candidiasis

Management Approach

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, 3

• Source control with appropriate drainage and/or debridement is mandatory 1, 3
• Antifungal choice is the same as for candidemia or empiric therapy in non-neutropenic ICU patients 1
• Duration determined by adequacy of source control and clinical response 1

Candida Endophthalmitis

Chorioretinitis Without Vitritis

• Fluconazole 400-800 mg (6-12 mg/kg) daily OR lipid formulation amphotericin B 3-5 mg/kg daily with or without flucytosine 25 mg/kg four times daily 1
• Duration: at least 4-6 weeks, dependent on resolution by repeated ophthalmological examinations 1

Chorioretinitis With Vitritis

Systemic antifungal therapy PLUS intravitreal injection 1:

• Amphotericin B deoxycholate 5-10 μg/0.1 mL sterile water, OR
• Voriconazole 100 μg/0.1 mL sterile water or normal saline 1
• Vitrectomy should be considered to decrease organism burden and remove inaccessible fungal abscesses 1
• Duration: at least 4-6 weeks, dependent on lesion resolution 1

Candida Endocarditis

Initial Therapy

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 100 mg daily) 1, 3

Oropharyngeal and Esophageal Candidiasis

Oropharyngeal Disease

• Mild disease: Topical clotrimazole troches 10 mg five times daily for 7-14 days 3
• Moderate to severe: Oral fluconazole 100-200 mg daily for 7-14 days 3
• Nystatin suspension 100,000 U/mL, 4-6 mL four times daily for 7-14 days is appropriate for superficial disease 2

Esophageal Candidiasis

Fluconazole 200-400 mg daily for 14-21 days is first-line therapy 3, 4

• For patients unable to tolerate oral therapy: IV fluconazole 400 mg daily or an echinocandin 3
• Chronic suppressive therapy with fluconazole 100-200 mg three times weekly for recurrent disease 3
• Antiretroviral therapy is strongly recommended for HIV-infected patients to reduce recurrence 3

Respiratory Candidiasis

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

Special Populations and Considerations

Diabetic and Immunocompromised Patients

For suspected invasive or systemic Candida infections, systemic azoles or echinocandins are required—neither butenafine nor nystatin is appropriate 2

• Corticosteroids (e.g., methylprednisolone) are known risk factors for invasive candidiasis 2
• Antifungal therapy should continue throughout periods of immunosuppression to prevent relapse 2

Prophylaxis in High-Risk Settings

• In nurseries with high rates (>10%) of invasive candidiasis: fluconazole prophylaxis 3-6 mg/kg twice weekly 1
• Daily bathing of ICU patients with chlorhexidine may decrease candidemia incidence 1

Critical Pitfalls to Avoid

Drug Interactions

Avoid concomitant fluconazole and clopidogrel—significant drug interaction reduces antiplatelet efficacy by 25-30% 3

Treatment Duration

Premature discontinuation leads to relapse—complete the full treatment course after bloodstream clearance 3

Hepatic Impairment

• Voriconazole maintenance dose should be reduced in mild to moderate hepatic impairment (Child-Pugh Class A and B) 4
• No dosage adjustment data available for severe hepatic impairment (Child-Pugh Class C) 4

Administration

• Voriconazole tablets must be administered at least one hour before or after a meal 4
• Switching between IV and oral voriconazole is appropriate due to high oral bioavailability 4