What is the recommended treatment for candidiasis (fungal infection) in patients with varying severity and location of infection, including those with weakened immune systems?

Candidiasis Treatment

Treatment by Anatomic Site and Severity

For candidiasis, treatment must be stratified by anatomic location, disease severity, and immune status, with fluconazole as first-line for most mucosal infections and echinocandins preferred for invasive disease in critically ill patients. 1

Oropharyngeal Candidiasis

Mild Disease:

• Topical therapy is first-line for mild oropharyngeal candidiasis 2, 1
• Clotrimazole troches 10 mg 5 times daily for 7-14 days 2
• Alternative: Miconazole mucoadhesive buccal 50 mg tablet once daily for 7-14 days 2
• Nystatin suspension (100,000 U/mL) 4-6 mL 4 times daily or nystatin pastilles (200,000 U each) 1-2 tablets 4 times daily for 7-14 days 2

Moderate to Severe Disease:

• Oral fluconazole 100-200 mg daily for 7-14 days is superior to topical therapy and prevents early symptomatic relapses, particularly in HIV-infected patients 2, 1
• Clinical cure rates of 84-90% with fluconazole 3

Fluconazole-Refractory Disease:

• Itraconazole solution 200 mg once daily (responds in approximately two-thirds of cases) 2, 3
• Posaconazole suspension 400 mg twice daily for 3 days, then 400 mg daily for up to 28 days 2
• Voriconazole 200 mg twice daily 2
• Amphotericin B oral suspension 100 mg/mL 4 times daily 2
• Intravenous echinocandins as last resort: caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily 2, 3

Esophageal Candidiasis

Systemic therapy is always required for esophageal candidiasis 2

First-Line Treatment:

• Fluconazole 200-400 mg (3-6 mg/kg) daily for 14-21 days 2, 4
• A diagnostic trial of antifungal therapy is appropriate before endoscopy 2, 1
• For patients unable to tolerate oral therapy: intravenous fluconazole 400 mg daily, amphotericin B deoxycholate 0.3-0.7 mg/kg daily, or an echinocandin 2

Fluconazole-Refractory Disease:

• Itraconazole solution 200 mg daily 2
• Posaconazole suspension 400 mg twice daily 2
• Voriconazole 200 mg twice daily (IV or oral) for 14-21 days 2
• Micafungin 150 mg daily, caspofungin 50 mg daily, anidulafungin 200 mg daily, or amphotericin B deoxycholate 0.3-0.7 mg/kg daily 2

Candidemia and Invasive Candidiasis

Initial Therapy Selection Algorithm:

For hemodynamically stable patients without recent azole exposure and low risk for C. glabrata:

• Fluconazole is appropriate first-line therapy 1

For moderately severe to severe illness, recent azole exposure, or high risk for C. krusei/C. glabrata:

• Echinocandins are preferred initial therapy due to fungicidal activity, favorable safety profile, and minimal drug interactions 1
• Caspofungin 70 mg loading dose, then 50 mg daily 2
• Micafungin 100 mg daily 2
• Anidulafungin 200 mg loading dose, then 100 mg daily 2

Step-Down Therapy:

• Transition to fluconazole for clinically stable patients after initial echinocandin or amphotericin B therapy when organism is likely fluconazole-susceptible 1

Duration and Source Control:

• Treatment duration: 2 weeks after documented bloodstream clearance and symptom resolution 1
• Catheter removal is strongly recommended for all non-neutropenic patients with candidemia 1

Vulvovaginal Candidiasis

Uncomplicated Disease (90% of patients):

• Topical antifungal agents are recommended, with no single agent superior 2
• Single-dose oral fluconazole 150 mg achieves 55% therapeutic cure rate (comparable to 7-day intravaginal therapy) 4

Complicated Disease (10% of patients):

• Requires extended therapy: daily topical treatment or two 150 mg doses of fluconazole administered 72 hours apart 2

Candida Urinary Tract Infections

Most patients do NOT require treatment 2

Treatment Indications (High-Risk Groups Only):

• Neutropenic patients 2
• Very low-birth-weight infants (<1500 g) 2
• Patients undergoing urologic manipulation 2

Treatment Regimens:

• For fluconazole-susceptible organisms: fluconazole 200 mg (3 mg/kg) daily for 2 weeks 2
• For fluconazole-resistant C. glabrata: amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days OR oral flucytosine 25 mg/kg 4 times daily 2
• For 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 2

Critical Pitfall: Elimination of indwelling bladder catheters is recommended whenever feasible 2

Cutaneous Candidiasis

• Topical azoles and polyenes are effective: clotrimazole, miconazole, or nystatin 2
• Keeping the infected area dry is essential 2
• For paronychia, drainage is the most important intervention 2

Central Nervous System Candidiasis

Initial Treatment:

• Liposomal amphotericin B 5 mg/kg daily, with or without oral flucytosine 25 mg/kg 4 times daily 2

Step-Down Therapy:

• Fluconazole 400-800 mg (6-12 mg/kg) daily after patient responds to initial treatment 2

Duration:

• Continue until all signs, symptoms, CSF, and radiological abnormalities have resolved 2
• Infected CNS devices should be removed if possible 2

Special Populations

Immunosuppressed Patients

• Higher threshold for echinocandin use given increased risk of azole-resistant species 1
• Fluconazole resistance predominantly results from repeated, long-term azole exposure, particularly in patients with advanced immunosuppression (CD4 <50 cells/μL) 1
• Non-albicans species (C. glabrata) increasingly cause refractory mucosal candidiasis in severely immunosuppressed patients 1

Recurrent Infections

Chronic Suppressive Therapy:

• Fluconazole 100-200 mg three times weekly for recurrent oropharyngeal or esophageal candidiasis 2, 5, 3
• Suppressive therapy should only be used if recurrences are frequent or disabling to reduce likelihood of antifungal resistance 2, 3
• For HIV patients: HAART is recommended to reduce recurrent infections 2

Denture-Related Disease:

• Thorough disinfection of dentures is essential and required for definitive cure 2, 3

Common Pitfalls and How to Avoid Them

Respiratory Tract Cultures:

• Do NOT initiate antifungal therapy based on respiratory tract culture results alone 2
• Candida pneumonia is extremely rare, and growth from respiratory secretions (including bronchoalveolar lavage) has poor predictive value for invasive disease 2

Treatment Duration:

• Complete the full 7-14 day course once symptoms resolve - inadequate treatment duration is a major cause of recurrence 3

Refractory Disease:

• Perform antifungal susceptibility testing to guide therapy in refractory cases, as it is predictive of clinical response to fluconazole and itraconazole 3

Addressing Underlying Factors:

• Optimize glycemic control in diabetic patients as the single best preventive measure 3
• Remove or address predisposing factors (indwelling catheters, dentures, immunosuppression) whenever possible 2, 3