Treatment Approach for Candidiasis

Initial Therapy Selection Based on Severity and Patient Status

For moderately severe to severe invasive candidiasis or candidemia, initiate an echinocandin immediately as first-line therapy (caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily) 1. This recommendation is particularly critical for critically ill patients, those with recent azole exposure, neutropenic patients, and hemodynamically unstable patients 2, 1.

Severity-Based Treatment Algorithm

Critically Ill/Moderately Severe Disease:

Start with an echinocandin as the preferred agent due to superior outcomes, fungicidal activity against all Candida species, favorable safety profile, and minimal drug interactions 2, 1
Echinocandins demonstrate ~75% success rates in randomized trials and are strongly favored for patients with hemodynamic instability 2
The 2016 IDSA guidelines explicitly favor echinocandins over fluconazole for severely ill patients based on mortality data 1

Mild to Moderate Disease (Hemodynamically Stable):

Fluconazole (800 mg loading dose, then 400 mg daily) is acceptable only when the patient has no recent azole exposure, is clinically stable, and infection is likely due to susceptible species (C. albicans, C. tropicalis, C. parapsilosis) 2, 1
Fluconazole remains standard therapy for selected patients based on abundant clinical trial data showing similar efficacy to amphotericin B in non-critically ill patients 2

Critical Pitfall: Do not delay antifungal therapy—initiate treatment within 24 hours of positive blood culture, as delays are associated with significantly increased mortality 2, 1.

Species-Specific Treatment Considerations

The choice of antifungal must account for species-specific susceptibility patterns:

For Candida glabrata:

Echinocandin is strongly preferred due to reduced azole susceptibility 2, 1
Do not transition to fluconazole or voriconazole without documented susceptibility testing 1
C. glabrata often has reduced susceptibility to both azoles and amphotericin B 2

For Candida parapsilosis:

Fluconazole is preferred over echinocandins due to decreased in vitro echinocandin activity against this species 2, 1
However, continuing an echinocandin is reasonable if the patient is clinically improved with negative follow-up cultures 1
C. parapsilosis candidemia is frequently catheter-associated and has lower mortality than other species 2

For Candida krusei:

Use echinocandin, lipid formulation amphotericin B (3-5 mg/kg daily), or voriconazole 1
Never use fluconazole due to intrinsic resistance 2, 1

For Candida albicans, C. tropicalis:

Either fluconazole or echinocandin is appropriate depending on severity 2

Source Control: Central Venous Catheter Management

Remove all indwelling central venous catheters as early as possible in all patients with candidemia 2. This is one of the most critical interventions:

CVC removal is associated with higher treatment success rates and lower mortality compared to catheter retention 2
The majority of candidemia patients have indwelling CVCs when blood cultures become positive 2
Urgent removal is mandatory for patients with septic shock 2
For clinically stable patients with limited vascular access, immediate removal may be deferred but should occur as soon as feasible 2
C. parapsilosis is particularly associated with CVC infection, making catheter removal especially important 2

Step-Down and De-escalation Strategy

Transition from echinocandin to fluconazole (400 mg daily) when:

The patient is clinically stable
Blood cultures have cleared
The isolate is confirmed or likely susceptible to fluconazole (C. albicans, C. parapsilosis, C. tropicalis) 2, 1

This de-escalation approach is supported by the 2016 IDSA guidelines and allows for potential completion with oral therapy 1. A short course of intravenous echinocandin (3-5 days) followed by transition to oral fluconazole or voriconazole (for C. krusei) is reasonable, though clinical data supporting this are limited 2.

Critical Pitfall: Do not transition to azoles without susceptibility confirmation, especially for C. glabrata and C. krusei 1.

Duration of Therapy and Monitoring

Treatment duration: Continue antifungal therapy for 2 weeks after documented clearance of Candida from bloodstream AND resolution of symptoms 2, 1.

Blood culture monitoring:

Obtain blood cultures daily or every other day until cultures no longer yield yeast 1
This monitoring is essential to document clearance and guide duration decisions 2

Ophthalmologic evaluation:

All patients with candidemia should undergo dilated fundoscopic examination to exclude endophthalmitis 2
Patients with suspected endocardial or CNS involvement should receive fungicidal agents (amphotericin B or echinocandin) rather than fluconazole as initial therapy 2

Alternative Agents and Special Situations

Amphotericin B formulations:

Reserved for intolerance or limited availability of echinocandins and azoles 1
Amphotericin B deoxycholate (0.5-1.0 mg/kg daily) or lipid formulations (3-5 mg/kg daily) 2, 1
Lipid formulations (ABLC, liposomal amphotericin B) are indicated for patients intolerant of or refractory to conventional therapy 2
Amphotericin B-induced nephrotoxicity can complicate management of critically ill patients 2

Voriconazole:

Has activity against most Candida species including C. krusei 2
Less attractive as initial therapy due to more frequent administration, less predictable pharmacokinetics, more drug interactions, and poor tolerance compared to other agents 2
Does not provide predictable activity against fluconazole-resistant C. glabrata 2
Fills an important niche for transition to oral therapy in patients with fluconazole-resistant isolates that have documented voriconazole susceptibility 2

Combination therapy:

A combination of fluconazole (800 mg/day) plus amphotericin B deoxycholate (0.7 mg/kg/day for the first 5-6 days) showed a trend toward better response based on more effective bloodstream clearance 2

Site-Specific Considerations

Candidemia without deep-seated infection:

Follow the severity-based algorithm above 2, 1

Chronic disseminated candidiasis:

Requires prolonged therapy until calcification or resolution of lesions 2
Premature discontinuation leads to recurrent infection 2, 1
Patients may continue chemotherapy during treatment 2

Candida peritonitis:

Requires surgical repair, drainage, and systemic antifungal therapy with either amphotericin B or fluconazole 2
Catheter-associated peritonitis requires catheter removal and at least 2-week delay before new catheter placement 2

Endocarditis/pericarditis:

Almost always requires combined medical and surgical therapy with valve removal or debridement 2
Medical therapy alone is insufficient—one case required 160 days of amphotericin B without sterilization 2

Cutaneous and Mucosal Candidiasis

Cutaneous candidiasis (immunocompetent patients):

Apply topical azole antifungals (clotrimazole 1% or miconazole 2% cream) twice daily for 7-14 days with complete cure rates of 73-100% 3
Keep affected areas dry, especially in skin folds 3
If topical treatment fails after 2 weeks, switch to oral fluconazole 150-200 mg daily for 7-14 days 3

Cutaneous candidiasis (immunocompromised patients):

Patients with neutropenia or severe immunosuppression may have disseminated disease and require aggressive systemic therapy starting with an echinocandin 3
Up to 13% of invasive disseminated candidiasis cases develop cutaneous manifestations 3

Esophageal candidiasis:

Micafungin 150 mg/day or fluconazole 200 mg/day are equally effective with endoscopic cure rates of ~88% 4
Most cases are due to C. albicans (96% in clinical trials) 4

Neonates with disseminated cutaneous candidiasis:

Healthy term infants require only topical therapy 3
Premature neonates, low-birth weight infants, or those with prolonged rupture of membranes must receive systemic amphotericin B (0.5-1 mg/kg/day for total dose of 10-25 mg/kg) to prevent lethal invasive candidiasis 3

Diagnostic Adjuncts to Guide Therapy

Risk stratification tools:

The Candida Score (CS) uses surgery, multifocal colonization, total parenteral nutrition, and severe sepsis (2 points) to predict invasive candidiasis; cutoff of 2.5 has 81% sensitivity and 74% specificity 2
An integrated strategy with beta-D-glucan (BG) and CS helped withhold or discontinue treatment in ICU patients with sepsis and CS >3 without increasing mortality 2

Biomarkers:

Beta-D-glucan has 56-93% sensitivity and 71-100% specificity for invasive candidiasis 2
High negative predictive value makes BG useful for discontinuing empirical therapy 2
Mannan antigen combined with anti-mannan IgG has 83% sensitivity and 86% specificity 2
Blood cultures are negative in up to 50% of invasive candidiasis cases 2

Susceptibility testing:

Useful adjunct to species identification for selecting therapeutic approach 2
Can identify isolates unlikely to respond to fluconazole or amphotericin B 2

Common Pitfalls to Avoid

Do not use fluconazole empirically in severely ill patients—echinocandins are superior 1
Do not delay antifungal initiation—start within 24 hours of positive blood culture 1
Do not prematurely discontinue therapy—leads to relapse, especially in chronic disseminated candidiasis 2, 1
Do not retain central venous catheters—removal is associated with better outcomes 2
Do not transition to azoles without susceptibility data for C. glabrata or C. krusei 1
Do not use topical corticosteroids for extended periods in cutaneous candidiasis—they worsen fungal infections 3

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