Treatment of Candida parapsilosis with Azoles
Fluconazole is the recommended first-line treatment for Candida parapsilosis infections, with a loading dose of 800 mg (12 mg/kg) followed by 400 mg (6 mg/kg) daily. 1
Initial Treatment Selection
The choice between fluconazole and echinocandins for C. parapsilosis depends on clinical severity and prior azole exposure:
- Fluconazole is preferred for C. parapsilosis infections in patients who are less critically ill and have no recent azole exposure 1
- Echinocandins may be started initially in moderately severe to severely ill patients or those with recent azole exposure, but transition to fluconazole should be considered once the species is identified 1
- For patients already on an echinocandin who are clinically improved with negative follow-up cultures, continuing the echinocandin is reasonable 1
Rationale for Fluconazole Preference
C. parapsilosis demonstrates excellent susceptibility to fluconazole, with treatment efficacy rates of 93% in clinical studies 2. This species typically has higher MICs to echinocandins compared to other Candida species, making azoles the more appropriate choice 1. A recent observational study found no difference in 30-day mortality or persistent candidemia at 72 hours between echinocandin-based and azole-based therapy for C. parapsilosis candidemia 1.
Alternative Azole Options
- Voriconazole (400 mg twice daily for 2 doses, then 200 mg twice daily) is effective for candidemia but offers little advantage over fluconazole and is recommended primarily as step-down oral therapy 1
- Itraconazole has limited data and cannot be recommended for routine treatment 1
- Posaconazole lacks sufficient evidence for treatment of invasive C. parapsilosis infections 1
Treatment Duration and Monitoring
- Continue therapy for 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms 1
- Perform follow-up blood cultures daily or every other day to document clearance 1
- Remove central venous catheters as early as possible, as catheter removal is strongly recommended for nonneutropenic patients 1
- Perform dilated ophthalmological examination within the first week after diagnosis in all nonneutropenic patients 1
Critical Caveat: Emerging Azole Resistance
Fluconazole resistance in C. parapsilosis is an emerging problem that requires vigilance 3, 4. Resistance rates of 3-4% have been documented, with the Y132F mutation in ERG11 identified in approximately 45% of resistant isolates 3. Persistent azole-resistant clones have been documented in ICU settings over multi-year periods 4.
Key risk factors for resistance include:
- Long-term fluconazole prophylaxis (particularly in neonatal ICUs) 5
- Prior corticosteroid exposure 4
- Previous azole exposure 6
When to suspect resistance:
- Failure to respond to fluconazole therapy within 3-5 days 1
- Prior azole exposure in the patient or unit 6, 4
- Known institutional resistance patterns 3
In these scenarios, consider susceptibility testing and switching to an echinocandin or amphotericin B formulation (0.5-1.0 mg/kg daily for amphotericin B deoxycholate or 3-5 mg/kg daily for lipid formulations) 1.
Special Populations
Neonates: Fluconazole (6-12 mg/kg per day) has been used successfully, though amphotericin B deoxycholate remains preferred due to low toxicity and more extensive experience in this population 1
Hematologic patients: The same treatment algorithm applies, with rapid catheter removal recommended regardless of species 1