What is the recommended treatment for Candida infections?

Treatment of Candida Infections

Echinocandins (caspofungin, micafungin, or anidulafungin) are the first-line treatment for invasive candidiasis and candidemia in critically ill patients, while fluconazole remains appropriate for less severe infections caused by susceptible species. 1

Critical First Step: Distinguish Colonization from Infection

Before initiating antifungal therapy, confirm that treatment is actually needed:

• Candida isolated from respiratory secretions almost always represents colonization and should NOT be treated, even in intubated ICU patients—autopsy studies show that positive respiratory cultures have poor predictive value for actual pneumonia 2
• Asymptomatic candiduria does not require treatment unless the patient is neutropenic or undergoing urologic procedures 2
• Growth of Candida from any site requires clinical correlation with signs and symptoms of actual infection before starting therapy 2

Treatment by Site and Severity

Invasive Candidiasis and Candidemia

For critically ill patients or those with recent azole exposure:

• Echinocandins are the preferred first-line agents due to their broad activity and superior safety profile 1
  • Caspofungin: 70 mg loading dose, then 50 mg daily 1, 3
  • Micafungin: 100 mg daily 1, 3
  • Anidulafungin: 200 mg loading dose, then 100 mg daily 1, 3

For less critically ill patients without recent azole exposure:

• Fluconazole: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily is appropriate 1
• Transition from echinocandin to fluconazole is recommended once the patient is clinically stable and the isolate is confirmed susceptible (e.g., Candida albicans) 1

Essential concurrent interventions:

• Remove all central venous catheters if feasible—this is strongly recommended and significantly impacts outcomes 1, 2, 3
• Obtain susceptibility testing for all bloodstream isolates 3

Duration of therapy:

• Continue treatment for 2 weeks after documented clearance of Candida from bloodstream AND resolution of symptoms 1, 2, 3

Species-Specific Considerations

For Candida glabrata infections:

• Echinocandins are strongly preferred due to high rates of azole resistance 1, 3
• Do not transition to fluconazole or voriconazole without confirmed susceptibility testing 1
• Liposomal amphotericin B (3-5 mg/kg daily) is an alternative 3

For Candida parapsilosis infections:

• Fluconazole is preferred over echinocandins 1
• If already receiving an echinocandin with clinical improvement and negative follow-up cultures, continuing the echinocandin is reasonable 1

For Candida krusei infections:

• Consider C. krusei intrinsically resistant to fluconazole 4, 5
• Use echinocandin, liposomal amphotericin B, or voriconazole 3

CNS and Ocular Infections

Echinocandins are NOT recommended for CNS or ocular infections due to poor penetration 1

For CNS candidiasis (meningitis):

• Amphotericin B deoxycholate 1 mg/kg IV daily OR liposomal amphotericin B 5 mg/kg daily 2
• Consider adding flucytosine 25 mg/kg four times daily for salvage therapy 2
• Step-down to fluconazole 800 mg (12 mg/kg) daily for susceptible isolates 2
• Continue therapy until all signs, symptoms, CSF abnormalities, and radiological findings resolve 2

Intra-Abdominal Candidiasis

• Source control with drainage and/or debridement is mandatory 2
• Empiric antifungal therapy is indicated for patients with clinical evidence of intra-abdominal infection PLUS significant risk factors (recent abdominal surgery, anastomotic leaks, necrotizing pancreatitis) 2
• Follow the same treatment algorithm as candidemia: echinocandins for severe cases, fluconazole for susceptible species in stable patients 1, 2
• For critically ill patients, initial echinocandin therapy is recommended 1
• Fluconazole is appropriate if C. albicans is isolated 1

Oropharyngeal Candidiasis

For mild disease:

• Clotrimazole troches 10 mg 5 times daily for 7-14 days 1
• OR miconazole mucoadhesive buccal 50-mg tablet once daily for 7-14 days 1
• Alternatives: nystatin suspension (100,000 U/mL) 4-6 mL 4 times daily for 7-14 days 1

For moderate to severe disease:

• Oral fluconazole 100-200 mg daily for 7-14 days 1, 2

For fluconazole-refractory disease:

• Itraconazole solution 200 mg once daily OR posaconazole suspension 400 mg twice daily for 3 days then 400 mg daily, for up to 28 days 1
• Alternatives: voriconazole 200 mg twice daily 1
• Intravenous echinocandin for severe refractory cases 1

Esophageal Candidiasis

• Oral fluconazole 200-400 mg (3-6 mg/kg) daily for 14-21 days 1, 2
• For patients unable to tolerate oral therapy: IV fluconazole 400 mg (6 mg/kg) daily OR echinocandin (micafungin 150 mg daily, caspofungin 70 mg loading then 50 mg daily, or anidulafungin 200 mg daily) 1
• Treat for minimum of 3 weeks AND at least 2 weeks after symptom resolution 2
• For fluconazole-refractory disease: itraconazole solution 200 mg daily OR voriconazole 200 mg (3 mg/kg) twice daily for 14-21 days 1

Urinary Tract Candidiasis

• Asymptomatic candiduria rarely requires treatment—removal of urinary catheters is often sufficient 2
• For symptomatic cystitis or pyelonephritis: fluconazole 200 mg daily for 7-14 days 2
• Remove or replace urinary catheters and stents whenever possible 2

Vulvovaginal Candidiasis

For uncomplicated cases:

• Single dose fluconazole 150 mg PO OR topical azoles intravaginally for 1-7 days 2

For recurrent vulvovaginal candidiasis:

• Initial treatment with fluconazole 150 mg single dose, followed by maintenance therapy with fluconazole 150 mg weekly for 6 months 2

Endocarditis

• Liposomal amphotericin B 3-5 mg/kg daily ± flucytosine 25 mg/kg four times daily, OR high-dose echinocandin 2
• Valve replacement is strongly recommended 2
• Continue therapy for at least 6 weeks after surgery (longer if perivalvular abscess present) 2

Alternative Agents

Liposomal amphotericin B:

• 3-5 mg/kg daily is an effective alternative if there is intolerance to or limited availability of echinocandins 1
• Amphotericin B deoxycholate 0.5-1.0 mg/kg daily is less preferred due to toxicity 1

Voriconazole:

• 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily 1, 6
• 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
• Consider when additional mold coverage is desired 1

Newer agents:

• Rezafungin (new echinocandin), ibrexafungerp, and oteseconazole now complement the antifungal armamentarium for superficial candidiasis 1

Special Populations

Neutropenic Patients

• Empiric antifungal therapy for persistent fever despite 4-6 days of antibacterial therapy 2
• Amphotericin B 0.5-0.7 mg/kg/day OR liposomal amphotericin B 3 mg/kg/day 2
• Continue therapy until resolution of neutropenia 2

Neonates

• High-risk neonates in nurseries with >10% invasive candidiasis rates should receive fluconazole prophylaxis 3-6 mg/kg twice weekly 2
• For treatment, fluconazole is appropriate if C. albicans is isolated 1

HIV-Infected Patients

• Antiretroviral therapy is strongly recommended to reduce the incidence of recurrent infections 1
• For recurrent oropharyngeal or esophageal candidiasis, chronic suppressive therapy with fluconazole 100-200 mg 3 times weekly 1, 2

Common Pitfalls to Avoid

• Do not use fluconazole as first-line in critically ill patients—echinocandins have superior outcomes in this population 3
• Do not leave central venous catheters in place—catheter retention significantly worsens outcomes 3
• Do not use azoles empirically in patients who received azole prophylaxis—resistance is likely 3
• Do not stop therapy prematurely—ensure a full 2-week course after blood culture clearance 3
• Do not assume all Candida species have the same susceptibility—species identification and susceptibility testing are essential 3, 4
• Do not treat Candida colonization—particularly respiratory tract colonization, which almost never requires antifungal therapy 2
• Consider fluconazole resistance in C. glabrata (often reduced susceptibility) and intrinsic resistance in C. krusei 1, 4, 5

Antifungal Stewardship

• Incorporating antifungal stewardship measures into health-care systems is crucial for improving guideline adherence and ensuring appropriate use of antifungals 1
• A multipronged approach involving screening, isolation, and environmental cleaning is essential for controlling outbreaks, particularly with emerging resistant strains like Candida auris 1