From the Guidelines
Oral fluconazole is not recommended as initial therapy for candidemia, but can be considered for step-down therapy in clinically stable patients with susceptible isolates and documented bloodstream clearance. According to the 2016 clinical practice guideline for the management of candidiasis by the Infectious Diseases Society of America 1, an echinocandin is recommended as initial therapy due to its strong efficacy and moderate-quality evidence. The guideline suggests that fluconazole can be used as an alternative for patients who are not critically ill and have had no prior azole exposure, but this is based on weak recommendation and low-quality evidence 1.
Key considerations for the use of oral fluconazole in candidemia include:
- The patient's clinical stability and lack of critical illness
- The absence of prior azole exposure
- The susceptibility of the Candida isolate to fluconazole
- The need for documented bloodstream clearance before considering step-down therapy
The recommended dosing for fluconazole, when used, is an 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 1. However, the primary concern with using oral fluconazole as initial therapy is its potential lower efficacy against many Candida species, particularly those with reduced susceptibility or resistance to fluconazole, such as C. glabrata and C. krusei 1.
In clinical practice, the transition to oral fluconazole for step-down therapy typically occurs after clinical improvement and clearance of Candida from the bloodstream, usually after 5-7 days of intravenous therapy with an echinocandin or other recommended initial therapy 1. The total treatment duration for uncomplicated candidemia should be at least 14 days after the first negative blood culture and resolution of symptoms, as recommended by the guideline 1.
From the FDA Drug Label
Fluconazole tablets are indicated for the treatment of: ... systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia. In open noncomparative studies of relatively small numbers of patients, fluconazole tablets were also effective for the treatment of ... systemic Candida infections including candidemia, In a noncomparative study of children with serious systemic fungal infections, most of which were candidemia, the effectiveness of fluconazole was similar to that reported for the treatment of candidemia in adults
Oral fluconazole is indicated for the treatment of candidemia. The drug label supports the use of fluconazole for the treatment of systemic Candida infections, including candidemia, in both adults and children 2, 2.
From the Research
Oral Fluconazole for Candidemia
- Oral fluconazole is an effective treatment for candidemia, particularly for patients with Candida glabrata or other Candida species with decreased fluconazole susceptibility 3.
- High-dose fluconazole (loading dose of 1600 mg followed by 800 mg daily) is an alternative treatment option, but it may result in higher drug costs and toxicity 3.
- The cost-effectiveness of high-dose fluconazole is acceptable, with a cost-effectiveness rate of $55,526 per discounted life year (DLY) saved, unless the patient's physical age is 66 years or older 3.
Comparison with Other Antifungal Agents
- Echinocandins are a new class of antifungal drugs that have been shown to be effective in treating candidemia, with response rates comparable to those of amphotericin B and fluconazole 4.
- A systematic review and network meta-analysis found that echinocandins were associated with the highest rate of treatment success for invasive candidiasis, compared to amphotericin B and triazoles 5.
- Fluconazole is still a widely used and effective treatment for candidiasis, with a remarkable efficacy, favorable pharmacokinetics, and reassuring safety profile 6.
Treatment Guidelines
- The Infectious Diseases Society of America favors echinocandins as treatment for candidemia in selected settings, at least as initial therapy 7.
- Specific recommendations for the treatment of candidemia should be based on the patient's individual characteristics, such as age, comorbidities, and susceptibility of the Candida species 7.
- The choice of antifungal agent should also consider cost-effectiveness and the potential for resistance 7.