What is the use of fluconazole (antifungal medication) in treating fungal infections?

Use of Fluconazole in Treating Fungal Infections

Fluconazole is a triazole antifungal agent effective for treating Candida infections (including oropharyngeal, esophageal, urinary tract, and invasive candidiasis), cryptococcal meningitis, and for prophylaxis in immunocompromised patients, with dosing ranging from 100-800 mg daily depending on infection severity and site. 1, 2

Primary Indications and Dosing

Candida Infections

Esophageal Candidiasis (First-Line)

• Fluconazole 200-400 mg (3-6 mg/kg) IV or oral daily for 14-21 days until clinical improvement 3, 1
• IV and oral doses are identical due to rapid and nearly complete oral absorption; switch to oral when patient achieves clinical stability 1

Oropharyngeal Candidiasis

• Fluconazole 100-200 mg daily for 7-14 days (1-7 days in children) for uncomplicated disease 3, 1
• Alternative agents include nystatin suspension or itraconazole if fluconazole is not suitable 3

Invasive Candidiasis and Candidemia

• Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) daily for severe infections 1
• Continue for 2 weeks after first negative blood culture and resolution of symptoms 3
• For candidemia without persistent fungemia or metastatic complications, treat for 3 weeks 3

Urinary Tract Infections

• Symptomatic cystitis: Fluconazole 200 mg (3 mg/kg) daily for 14 days 3, 1
• Pyelonephritis: Fluconazole 200-400 mg (3-6 mg/kg) daily for 14 days 3, 1
• Asymptomatic cystitis typically requires no therapy unless patient is high-risk surgical, neonate, or neutropenic 3

CNS and Disseminated Infections

CNS Candidiasis

• Fluconazole 400-800 mg (6-12 mg/kg) daily for patients unable to tolerate amphotericin B 3, 1
• Remove intraventricular devices 3
• Treat until all signs, symptoms, CSF abnormalities, and radiologic abnormalities resolve 3
• Can use as step-down therapy in stable patients after initial amphotericin B 3

Chronic Disseminated Candidiasis

• Fluconazole as drug of choice, continued until lesions resolve (typically 3-6 months) 3, 1
• Can serve as step-down therapy in stable patients 3

Candida Endophthalmitis

• Fluconazole is an alternative option (amphotericin B with 5-FC is first-line) 3
• Duration at least 4-6 weeks, determined by repeated examinations 3

Cryptococcal Infections

Cryptococcal Meningitis

• Consolidation treatment: 400-600 mg daily for 8 weeks 1
• Maintenance treatment for AIDS patients: 200 mg daily for 6-12 months 1
• Fluconazole is the drug of choice for maintenance therapy following amphotericin B induction 4

Non-Meningeal Cryptococcosis

• Severe disease: treat as CNS disease for 12 months 1
• Mild-to-moderate disease: 400 mg daily for 6-12 months 1

Special Populations

Neonatal Candidiasis

• Fluconazole 12 mg/kg/day 3, 1
• Lumbar puncture and ophthalmoscopic examination recommended in neonates with positive sterile body fluid or urine cultures 3
• Imaging of genitourinary tract, liver, and spleen if cultures persistently positive 3

Neutropenic Patients

• Empirical therapy: fluconazole is an alternative option (amphotericin B or echinocandin preferred) 3
• Treat for 2 weeks after first negative blood culture, resolution of symptoms, and resolution of neutropenia 3

Prophylaxis in Bone Marrow Transplant

• Indicated to decrease incidence of candidiasis in patients receiving cytotoxic chemotherapy and/or radiation therapy 2

Critical Species-Specific Considerations

C. parapsilosis

• Fluconazole is a drug of choice 3
• If echinocandin used initially, consider changing to fluconazole 3

C. glabrata

• Fluconazole is an alternative only; continue only if patient clinically improved and follow-up cultures negative 3
• Do not change to fluconazole or voriconazole without confirmation of isolate susceptibility 3

C. krusei

• Fluconazole is NOT effective; C. krusei is intrinsically resistant 3, 1
• Use echinocandin or lipid formulation amphotericin B instead 3

Common Pitfalls and Caveats

Underdosing Severe Infections

• Use loading dose of 800 mg (12 mg/kg) for severe invasive infections 1
• Inadequate duration of treatment can lead to relapse 1

Renal Function Adjustment

• Dose should be adjusted according to renal function, as approximately 70% is excreted unchanged in urine 5, 1

Drug Interactions

• Monitor patients on coumarin anticoagulants closely 5
• Monitor patients taking oral hypoglycemics, as fluconazole inhibits tolbutamide metabolism 5
• No significant interaction with cyclosporine, cimetidine, or oral contraceptives 5

Resistance Patterns

• Always obtain specimens for fungal culture before initiating therapy 2
• Adjust therapy once susceptibility results available 2
• Consider echinocandin for species with known or suspected resistance 1

Relapse in Immunocompromised Patients

• Relapse of oral infection is common in chronically immunocompromised patients regardless of antifungal used 6
• Long-term prophylaxis appears necessary in patients with AIDS 6, 4

Tolerability Profile

Fluconazole is generally well tolerated with low incidence of serious adverse effects 6, 7, 5

• Most frequent adverse events: gastrointestinal complaints, headache, and skin rash 4
• Rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred 4
• Only 1.1-2% of patients discontinued therapy due to adverse effects 5, 8