What is the treatment regimen for Fluconazole in fungal infections?

Fluconazole Treatment Regimens for Fungal Infections

Fluconazole dosing and duration should be tailored to the specific fungal infection type, with treatment generally continuing until clinical resolution and negative cultures, typically 14 days after clearance for candidemia. 1

General Dosing Principles

Candidemia and Invasive Candidiasis

• Initial therapy:
  • Loading dose: 800 mg (12 mg/kg) on day 1
  • Maintenance: 400 mg (6 mg/kg) daily 1, 2
  • Duration: 2 weeks after documented clearance of Candida from bloodstream and resolution of symptoms 1
  • Important: Remove intravascular catheters when possible 1

Species-Specific Considerations

• C. albicans: Fluconazole is first-line therapy for less critically ill patients 1
• C. parapsilosis: Fluconazole is preferred (even as step-down from echinocandins) 1
• C. glabrata: Echinocandins preferred; fluconazole only with confirmed susceptibility 1
• C. krusei: Avoid fluconazole (intrinsic resistance) 3

Infection-Specific Regimens

Mucocutaneous Candidiasis

• Oropharyngeal candidiasis:

  • 100-200 mg daily for 7-14 days (1-7 days in children) 1, 2
  • Alternative: Nystatin suspension 200,000-400,000 U four times daily 1

• Esophageal candidiasis:

  • 200-400 mg daily for 14-21 days until clinical improvement 1, 2
  • Alternative: Itraconazole 200 mg daily 1

Urinary Tract Infections

• Symptomatic cystitis: 200 mg (3 mg/kg) daily for 14 days 1, 2
• Pyelonephritis: 200-400 mg (3-6 mg/kg) daily for 14 days 1, 2
• Asymptomatic candiduria: Treatment not usually needed except in high-risk patients 1

CNS Candidiasis

• Dosage: 400-800 mg (6-12 mg/kg) daily 1
• Duration: Until all signs, symptoms, CSF abnormalities, and radiological abnormalities resolve 1
• Note: Remove infected CNS devices if possible 1

Chronic Disseminated Candidiasis

• Duration: Continue until lesions resolve (typically 3-6 months) 1, 2
• Step-down therapy: Fluconazole can be used in stable patients 1

Neonatal Candidiasis

• Dosage: 12 mg/kg daily 1
• Duration: 3 weeks for candidemia without persistent fungemia or metastatic complications 1

Candida Endophthalmitis

• Duration: At least 4-6 weeks, determined by repeated examinations to verify resolution 1
• Note: Consider surgical intervention for severe endophthalmitis or vitreitis 1

Special Considerations

Renal Impairment

• CrCl 11-50 mL/min: 50% of standard dose
• CrCl <10 mL/min: 25% of standard dose 2

Monitoring

• Efficacy: Clinical response within 7-10 days 2
• Safety: Monitor liver function tests every 1-2 weeks during treatment 2
• Candidemia: Perform ophthalmological examination 2

Potential Adverse Effects

• Hepatotoxicity: Monitor liver function tests; discontinue if signs of liver disease develop 4
• QT prolongation: Use with caution in patients with cardiac conditions or electrolyte abnormalities 4
• Drug interactions: Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor and strong CYP2C19 inhibitor 4

Step-Down Therapy

• Consider transitioning from echinocandins to fluconazole for patients with isolates likely to be susceptible (e.g., C. albicans) who are clinically stable 1
• For C. glabrata, confirm susceptibility before transitioning to fluconazole 1

Common Pitfalls

1. Failure to adjust dose in renal impairment can lead to toxicity
2. Not removing intravascular catheters in candidemia may result in persistent infection
3. Inadequate treatment duration increases risk of relapse
4. Using fluconazole for C. krusei infections (intrinsically resistant)
5. Overlooking drug interactions with medications that prolong QT interval or are metabolized by CYP enzymes

By following these evidence-based regimens and considering patient-specific factors, fluconazole can be effectively used to treat a wide range of fungal infections.