Treatment of Candida auris Meningitis
For C. auris meningitis, initiate liposomal amphotericin B 5 mg/kg daily combined with flucytosine 25 mg/kg four times daily, with mandatory removal of any CNS devices (shunts, drains), and plan for prolonged therapy of at least 10 weeks followed by fluconazole suppression if the isolate is susceptible. 1
Critical Initial Management
Immediate Antifungal Therapy
Start liposomal amphotericin B 5 mg/kg daily as the preferred amphotericin formulation due to better CNS penetration and lower toxicity compared to amphotericin B deoxycholate 1
Add flucytosine 25 mg/kg four times daily to the regimen, with dose adjustment to maintain serum levels of 40-60 mg/mL through therapeutic drug monitoring 1
Echinocandins (caspofungin, micafungin, anidulafungin) have poor CNS penetration and should not be used as primary therapy for meningitis, though they may be considered for salvage therapy in refractory cases 1
Device Management
Remove all infected CNS devices immediately (ventriculostomy drains, shunts, external ventricular drains) as they serve as biofilm reservoirs and prevent cure 1
Device removal is mandatory and non-negotiable for successful treatment outcomes 1
Species-Specific Considerations for C. auris
Resistance Profile Awareness
C. auris demonstrates extensive antifungal resistance: only 10.7% susceptible to fluconazole and 43.1% susceptible to amphotericin B in COVID-19 patients 1
Echinocandins show better susceptibility (90% to caspofungin, 98.2% to micafungin, 97.2% to anidulafungin), but their poor CNS penetration limits utility in meningitis 1
Obtain antifungal susceptibility testing immediately to guide definitive therapy 2, 3
Treatment Duration and Monitoring
Prolonged Therapy Requirements
Continue combination therapy with liposomal amphotericin B plus flucytosine for at least 10 weeks based on successful neonatal case reports extrapolated to adults 1
Therapy must continue until all of the following are achieved: normalization of CSF parameters (cell count, glucose, protein), resolution of radiological abnormalities on MRI, and stabilization of neurological function 1
The minimum duration is 4 weeks after resolution of all signs and symptoms, though C. auris may require longer treatment given its resistance profile 1
Step-Down and Suppressive Therapy
After initial response to amphotericin-based therapy, transition to fluconazole 800 mg daily (12 mg/kg) for susceptible isolates only 1
If fluconazole resistance is documented, consider voriconazole 400 mg twice daily loading dose, then 200 mg twice daily with therapeutic drug monitoring, though CSF concentrations are variable 1
Lifelong suppressive therapy may be necessary given C. auris's propensity for relapse and multidrug resistance 1, 2, 4
Alternative and Salvage Regimens
For Refractory Cases
Intraventricular caspofungin 10 mg daily has been used successfully in one reported case of multidrug-resistant C. auris shunt infection when systemic therapy failed 5
This approach requires neurosurgical expertise and should be reserved for cases failing systemic therapy 5
Voriconazole combined with fluconazole (voriconazole 12/6 mg/kg plus fluconazole 6 mg/kg for 4 weeks) represents an alternative azole-based regimen if amphotericin cannot be used 1
Monitoring and Follow-Up
Essential Assessments
Perform serial lumbar punctures to document CSF sterilization and normalization of parameters (typically weekly initially, then less frequently) 1
Obtain brain MRI with and without contrast at baseline and periodically to assess for complications like hydrocephalus, abscesses, or vascular involvement 1
Monitor for hydrocephalus development, which may require shunt placement even during successful antifungal therapy 1
Check flucytosine serum levels regularly to maintain therapeutic range of 40-60 mg/mL and avoid bone marrow toxicity 1
Critical Pitfalls to Avoid
Do not use fluconazole as initial therapy for C. auris meningitis given the 89.3% resistance rate 1, 2, 4
Do not rely on echinocandins alone for CNS infection despite their activity against C. auris, as they penetrate poorly into CSF 1
Do not discontinue therapy prematurely even if CSF cultures become negative, as parenchymal infection may persist after CSF sterilization 1
Do not delay device removal in hopes that antimicrobials alone will cure the infection 1, 5
Recognize that C. auris is frequently misidentified by traditional biochemical methods; ensure proper species identification using MALDI-TOF or molecular methods 2, 3