What is the best course of treatment for a 29-year-old male with a history of recurrent fungal infection, previously successfully treated with fluconazole (fluconazole) 150mg weekly for 4 weeks, who has mild impaired renal function (eGFR 77, CKD category G2), and is currently taking levothyroxine (levothyroxine) for hypothyroidism, diclofenac (diclofenac) 1% gel, and naproxen (naproxen), and has shown significant improvement in bilirubin levels?

Fluconazole Resumption for Recurrent Fungal Infection

Direct Recommendation

You can safely resume fluconazole 150 mg weekly for this patient's recurrent fungal infection, as his mild renal impairment (eGFR 77) does not require dose adjustment and his bilirubin has normalized, indicating no significant hepatic concern. 1

Clinical Reasoning

Renal Function Assessment

• No dose adjustment is needed for eGFR 77 (CKD G2). Fluconazole dose adjustment is only required when creatinine clearance falls below 50 mL/min 1
• The patient's eGFR of 77 mL/min is well above this threshold, allowing standard dosing without modification 1
• Fluconazole is primarily eliminated renally (approximately 60% recovered unchanged in urine within 48 hours), but this level of renal function is adequate for standard dosing 2, 3

Hepatic Safety Profile

• The normalized bilirubin (1.1 mg/dL, down from 1.6 mg/dL) and consistently normal transaminases (AST 17, ALT 10) indicate no hepatotoxicity concern 4
• Fluconazole-associated liver injury occurs in <10% of patients and is typically transient 5
• The patient's previous 4-week course was well-tolerated without hepatotoxicity symptoms, which is reassuring for retreatment 4
• Monitor liver function during therapy, particularly given concurrent NSAID use (diclofenac and naproxen), though the patient's baseline hepatic function is excellent 4, 6

Appropriate Dosing Regimen

For recurrent fungal infections (≥4 episodes per year), the IDSA recommends:

1. Induction phase: 10-14 days of oral fluconazole or topical azole therapy to achieve initial control 7, 8

   • For oral fluconazole: 150 mg every 72 hours for 2-3 doses (total 10-14 days) 8

2. Maintenance suppressive therapy: Fluconazole 150 mg orally once weekly for 6 months 7, 8

   • This achieves symptom control in >90% of patients 7
   • This is the most convenient and well-tolerated regimen 8

Critical Management Points

Address any predisposing factors before initiating suppressive therapy (diabetes, immunosuppression, etc.) 8

Set realistic expectations: After cessation of the 6-month maintenance regimen, expect 40-50% recurrence rate 7, 8

Drug Interaction Considerations

• Levothyroxine: No significant interaction with fluconazole; continue current dose 1
• NSAIDs (diclofenac, naproxen): While both NSAIDs and fluconazole can affect liver function independently, the patient's excellent baseline hepatic function and previous tolerance make concurrent use acceptable with monitoring 4, 6
• Monitor for additive hepatotoxicity risk, though the patient's normal transaminases provide reassurance 6

Monitoring Plan

During fluconazole therapy, monitor:

• Liver function tests if symptoms develop (jaundice, dark urine, abdominal pain, unusual fatigue) 4
• Renal function given baseline CKD G2, though no immediate concern exists 1
• Clinical response to therapy within 7-14 days 9

Common Pitfalls to Avoid

Do not use single-dose fluconazole for dermatophyte infections (tinea corporis, tinea pedis) - the 150 mg single dose is only appropriate for vulvovaginal candidiasis 9, 1

Ensure adequate treatment duration - premature discontinuation leads to recurrence 1

Confirm fungal species if possible - while most recurrent infections are azole-susceptible C. albicans, C. glabrata may require alternative therapy (boric acid 600 mg intravaginally daily for 14 days) 8