What is the recommended treatment for a patient with a Candida spp infection?

Treatment of Candida Species Infections

For candidemia and invasive candidiasis, initiate an echinocandin (caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily) as first-line therapy for critically ill patients or those with recent azole exposure, while fluconazole 800 mg loading dose then 400 mg daily is appropriate for stable, non-critically ill patients without prior azole exposure. 1, 2

Candidemia and Invasive Candidiasis

Initial Therapy Selection

The choice between echinocandins and fluconazole depends on illness severity and azole exposure history:

• Echinocandins are preferred for moderately severe to severe illness, recent azole exposure, or critically ill patients 1, 3
• Fluconazole is appropriate for less critically ill, hemodynamically stable patients without recent azole exposure 1, 2, 3
• Start antifungal therapy within 24 hours of positive blood culture 1

Species-Specific Considerations

Treatment must be adjusted based on the identified Candida species:

• C. albicans: Either echinocandin or fluconazole acceptable; transition from echinocandin to fluconazole is reasonable once clinically stable 1
• C. glabrata: Echinocandin strongly preferred due to reduced azole susceptibility; do not transition to azole without documented susceptibility testing 1, 3
• C. parapsilosis: Fluconazole preferred over echinocandins due to decreased echinocandin activity against this species 1, 3
• C. krusei: Avoid fluconazole entirely (intrinsically resistant); use echinocandin or amphotericin B 3

Duration and Monitoring

• Continue therapy for 2 weeks after documented bloodstream clearance and resolution of symptoms 1, 2
• Obtain follow-up blood cultures daily or every other day until negative 1
• Perform ophthalmologic examination for all candidemia patients to detect endophthalmitis 1

Catheter Management

• Remove all intravascular catheters if possible in non-neutropenic patients with candidemia 1, 2
• Catheter removal is strongly recommended and associated with improved outcomes 2

Oropharyngeal and Esophageal Candidiasis

Oropharyngeal Disease

• Mild disease: Clotrimazole troches 10 mg five times daily for 7-14 days 2, 3
• Moderate to severe disease: Fluconazole 100-200 mg daily for 7-14 days 2, 3
• Treat for at least 2 weeks to decrease relapse likelihood 4

Esophageal Disease

• First-line: Fluconazole 200-400 mg daily for minimum 14-21 days and at least 7 days after symptom resolution 2, 3, 4
• For patients unable to tolerate oral therapy, use IV fluconazole 400 mg daily or an echinocandin 2
• Doses up to 12 mg/kg/day may be used in children based on response 4

Urinary Tract Candidiasis

Asymptomatic Candiduria

• Generally no treatment indicated unless high-risk patient (neutropenic, neonate) or undergoing urologic procedures 1
• Remove indwelling catheters when feasible 3

Symptomatic Cystitis

• Fluconazole 200 mg daily for 2 weeks for fluconazole-susceptible organisms 1, 3
• Amphotericin B 0.3-0.6 mg/kg daily for 1-7 days for fluconazole-resistant organisms 1

Pyelonephritis

• Fluconazole 200-400 mg daily for 2 weeks 1
• Amphotericin B 0.5-0.7 mg/kg daily with or without flucytosine 25 mg/kg four times daily for resistant organisms 1

Neutropenic Patients

• Echinocandin, lipid formulation amphotericin B 3-5 mg/kg daily, or fluconazole 800 mg loading then 400 mg daily 1
• Fluconazole appropriate only for patients without recent azole exposure who are not critically ill 1
• Voriconazole 400 mg twice daily for 2 doses then 200 mg twice daily when additional mold coverage desired 1
• Do not use azoles in patients receiving azole prophylaxis 1
• Catheter removal controversial but advised when possible 1

Central Nervous System Candidiasis

• Amphotericin B deoxycholate 1 mg/kg IV daily as initial treatment 2
• Liposomal amphotericin B 5 mg/kg daily is an alternative 2
• For cryptococcal meningitis: 400 mg fluconazole on day 1, then 200-400 mg daily for 10-12 weeks after CSF culture negative 4

Neonatal Candidiasis

• Amphotericin B deoxycholate 1 mg/kg IV daily as first-line therapy 2, 3
• Fluconazole 12 mg/kg IV or oral daily is alternative in patients not on fluconazole prophylaxis 3
• Mandatory lumbar puncture and dilated retinal examination in neonates with positive blood/urine cultures 2
• For premature newborns (gestational age 26-29 weeks), administer same mg/kg dose every 72 hours for first 2 weeks of life, then daily 4

Vulvovaginal Candidiasis

• Uncomplicated disease: Fluconazole 150 mg single oral dose or topical azoles (clotrimazole, miconazole) for 1-7 days 3
• Severe disease: Two sequential 150 mg fluconazole doses given 3 days apart achieve superior clinical and mycologic cure compared to single dose 5
• Non-albicans Candida predicts reduced response regardless of therapy duration 5

Alternative Agents

Amphotericin B Formulations

• Amphotericin B deoxycholate 0.5-1.0 mg/kg daily or lipid formulation 3-5 mg/kg daily when intolerance or limited availability of other antifungals 1
• Transition to fluconazole appropriate once clinically stable with susceptible isolate 1

Voriconazole

• 400 mg twice daily for 2 doses, then 200 mg twice daily 1
• Effective for candidemia but offers little advantage over fluconazole 1
• Recommended as step-down oral therapy for C. krusei or voriconazole-susceptible C. glabrata 1

Renal Impairment Dosing

For fluconazole in patients receiving multiple doses 4:

• CrCl >50 mL/min: 100% of recommended dose
• CrCl ≤50 mL/min (no dialysis): 50% of recommended dose
• Hemodialysis: 100% of dose after each dialysis session

Give initial loading dose (50-400 mg) regardless of renal function 4

Critical Pitfalls to Avoid

• Avoid fluconazole with clopidogrel: Significant drug interaction reduces antiplatelet efficacy by 25-30% 2
• Do not use fluconazole for C. krusei: Intrinsically resistant 3, 6
• Exercise caution with C. glabrata: Reduced susceptibility; echinocandin preferred 1, 3
• Premature discontinuation leads to relapse: Complete full treatment course after bloodstream clearance 2
• Delayed therapy increases mortality: Initiate treatment within 24 hours of positive blood culture 1
• Do not interchange fluconazole oral solution and capsules: Different bioavailability and indications 7