What is the recommended antifungal prophylaxis for a patient with Chronic Kidney Disease (CKD) stage 5, Cervical Cancer stage 3, Severe Hydronephrosis, and fungal elements in the urine, with leukocytosis, thrombocytosis, and prolonged Activated Partial Thromboplastin Time (APTT)?

Antifungal Management for Funguria in CKD Stage 5 with Severe Hydronephrosis

This patient requires urgent relief of urinary tract obstruction followed by treatment-dose antifungal therapy, not prophylaxis, given the presence of fungal elements in urine with severe hydronephrosis and leukocytosis. 1

Critical First Step: Address Urinary Obstruction

• Elimination of urinary tract obstruction is strongly recommended as the priority intervention before or concurrent with antifungal therapy 1
• The severe hydronephrosis represents a urologic emergency requiring nephrostomy tube placement or ureteral stent insertion 1
• This patient likely has Candida pyelonephritis given the combination of funguria, hydronephrosis, and systemic inflammatory response (leukocytosis 18,300) 2

Antifungal Treatment Regimen (Not Prophylaxis)

Initial Empiric Therapy

Amphotericin B deoxycholate 0.3–0.6 mg/kg daily is the recommended initial treatment for this patient rather than fluconazole, given: 1

• CKD stage 5 with uncertain dialysis status
• Severe presentation with leukocytosis suggesting pyelonephritis
• Need for broad empiric coverage pending fungal speciation

Alternative if Fluconazole-Susceptible Species Confirmed

• If speciation reveals fluconazole-susceptible Candida (most commonly C. albicans), transition to fluconazole 200–400 mg (3–6 mg/kg) daily for 2 weeks 1, 2
• The higher dose (400 mg daily) is preferred given the severity of presentation with pyelonephritis 2
• However, fluconazole dosing in CKD stage 5 requires significant adjustment: standard dose is 50% of normal dose in patients on dialysis 3, 4

For Fluconazole-Resistant Species

• C. glabrata: Amphotericin B deoxycholate 0.3–0.6 mg/kg daily with or without flucytosine 25 mg/kg four times daily 1
• C. krusei: Amphotericin B deoxycholate 0.3–0.6 mg/kg daily 1
• Flucytosine requires dose reduction in renal failure and therapeutic drug monitoring 1

Critical Management Considerations

Why This is NOT Prophylaxis

• Antifungal prophylaxis is NOT indicated for asymptomatic candiduria 1
• Treatment is only recommended for high-risk patients: neutropenic patients, very low-birth-weight infants, or patients undergoing urologic manipulation 1
• This patient requires treatment (not prophylaxis) because of:
  • Severe hydronephrosis requiring urologic intervention 1
  • Leukocytosis suggesting invasive infection 2
  • Likely pyelonephritis based on clinical presentation 2

Exclude Disseminated Candidiasis

• Obtain blood cultures immediately to rule out candidemia, as patients with Candida pyelonephritis may have disseminated disease 2
• If candidemia is present, treat as disseminated candidiasis with an echinocandin (micafungin 100 mg daily, caspofungin 70 mg loading then 50 mg daily, or anidulafungin 200 mg loading then 100 mg daily) rather than fluconazole 1, 5

Coagulopathy Consideration

• The prolonged APTT (140 ms) is a critical finding that may complicate invasive procedures for obstruction relief 1
• This coagulopathy must be corrected before nephrostomy tube placement or stent insertion
• The coagulopathy does not contraindicate antifungal therapy but requires investigation (lupus anticoagulant, factor deficiency, or acquired inhibitor)

Device Management

• Remove or replace nephrostomy tubes or stents after placement if feasible during the treatment course 1
• If nephrostomy tubes remain in place, consider amphotericin B irrigation (25–50 mg in 200–500 mL sterile water) as adjunctive therapy 1

Common Pitfalls to Avoid

• Do not treat asymptomatic candiduria in non-high-risk patients – this leads to antifungal resistance without clinical benefit 1
• Do not use standard fluconazole doses in CKD stage 5 – this causes drug accumulation and potential toxicity 3, 4
• Do not delay obstruction relief – antifungals alone will fail without addressing the mechanical obstruction 1
• Do not assume this is simple cystitis – the combination of hydronephrosis and leukocytosis suggests upper tract involvement requiring more aggressive therapy 2
• Do not use azoles empirically if the patient has had recent azole exposure – this increases risk of resistant species 1

Treatment Duration

• Treat for 2 weeks after obstruction relief and clinical improvement for pyelonephritis 1, 2
• Continue until resolution of hydronephrosis is documented by imaging 1
• Monitor for treatment failure requiring transition to alternative agents based on susceptibility results 1, 2