What is the recommended dosage of Fluconazole (Diflucan) for Candida infection in the blood (Bacteremia)?

From the Guidelines

For the treatment of Candida infection in the blood (Bacteremia), the recommended dosage of Fluconazole (Diflucan) is an 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, for patients who are not critically ill and have had no prior azole exposure. This recommendation is based on the 2016 clinical practice guideline for the management of candidiasis by the Infectious Diseases Society of America 1.

Key Considerations

• The dosage is recommended for patients who are not critically ill and have had no prior azole exposure, as stated in the guideline 1.
• For patients who are critically ill or have had prior azole exposure, alternative treatments such as echinocandins or lipid formulation AmB may be recommended 1.
• The guideline also recommends a minimum duration of therapy for candidemia without metastatic complications of 2 weeks after documented clearance of Candida from the bloodstream, provided neutropenia and symptoms attributable to candidemia have resolved 1.

Important Details

• Fluconazole works by inhibiting fungal cytochrome P450 enzymes, preventing the synthesis of ergosterol, an essential component of fungal cell membranes.
• Oral administration is preferred due to its excellent bioavailability (>90%), but intravenous formulation is available for patients unable to take oral medications.
• Dose adjustment is necessary for patients with renal impairment (reduce by 50% if creatinine clearance is <50 mL/min).
• Before initiating treatment, confirm the Candida species as some (like C. krusei and often C. glabrata) have intrinsic resistance to fluconazole.
• Monitor liver function tests during treatment as fluconazole can cause hepatotoxicity.
• Be aware of drug interactions, particularly with medications metabolized by CYP3A4 enzymes.

From the FDA Drug Label

For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used The recommended dosage of Fluconazole for Candida infection in the blood (Bacteremia) is not established, but doses of up to 400 mg daily have been used in some studies 2.

From the Research

Recommended Dosage of Fluconazole for Candida Infection in the Blood

The recommended dosage of Fluconazole (Diflucan) for Candida infection in the blood (Bacteremia) varies depending on the species of Candida and the patient's condition.

• For Candida albicans, a dose of >200 mg/day, a dose/MIC ratio of >400, and an AUC24/MIC ratio of >400 are associated with a higher 30-day survival rate and better microbiological response 3.
• For non-albicans Candida, the optimal dosage is not well established, and severity of sepsis is a significant predictor of death 3.
• High-dose fluconazole (> or =600 mg/day) may be effective for susceptible dose-dependent Candida isolates, with a response rate of 95% in one study 4.
• A dose of 800 mg/day (approximately 12 mg/kg per day) is predicted to produce peak plasma concentrations that surpass the susceptible-dose-dependent MIC breakpoint of 16 to 32 mug/mL for Candida glabrata 5.

Dosage Adjustment

• Dosage adjustment may be necessary for patients with renal failure, with a maintenance dose that is adjusted for anuric patients by multiplying by a factor that takes into account the extracorporeal elimination of the absorbed dose 6.
• Higher doses of fluconazole (> or =400 mg/d) may be more likely to achieve fungemia eradication than lower doses (< or =400 mg/d) in patients with Candida glabrata fungemia 5.

Treatment Outcomes

• The response rate to fluconazole therapy for candidemia is approximately 70% with standard-dose fluconazole (400 mg/day) 4.
• High-dose fluconazole therapy may be associated with higher response rates than standard-dose fluconazole in a selected group of patients with solid tumors and candidemia caused by species that are susceptible to this triazole 4.
• Mortality rates for patients with Candida glabrata fungemia treated with fluconazole range from 24% to 40% 5.