From the Guidelines
Fluconazole can be effective against Candida glabrata, but its use is generally recommended at higher doses, such as 800 mg daily, and only in cases where the isolate is susceptible to fluconazole, as indicated by antifungal susceptibility testing 1. When treating C. glabrata infections, clinicians typically consider alternative antifungal medications, such as echinocandins (like caspofungin, micafungin, or anidulafungin) or amphotericin B formulations, as first-line treatments due to the reduced susceptibility of C. glabrata to fluconazole. The reduced susceptibility occurs because C. glabrata has mechanisms to pump fluconazole out of fungal cells and can upregulate these efflux pumps when exposed to the drug. Additionally, C. glabrata can develop mutations in the ERG11 gene, which encodes the target enzyme of fluconazole. Some key points to consider in the treatment of C. glabrata infections include:
- The use of fluconazole at higher doses, such as 800 mg daily, may be considered in cases where the isolate is susceptible to fluconazole 1.
- Echinocandins, such as caspofungin, micafungin, or anidulafungin, are often preferred as first-line treatments for C. glabrata infections due to their broader spectrum of activity and lower risk of resistance 1.
- Amphotericin B formulations, such as lipid formulation amphotericin B, may be considered as alternative treatments in cases where there is intolerance, limited availability, or resistance to other antifungal agents 1.
- Antifungal susceptibility testing is recommended to determine the effectiveness of fluconazole against the specific C. glabrata strain causing the infection 1.
From the Research
Effectiveness of Fluconazole Against Candida Glabrata
- The effectiveness of fluconazole against Candida glabrata is variable, with some studies indicating reduced susceptibility or resistance to fluconazole 2, 3, 4, 5.
- A study from 2011 found that fluconazole was less effective than posaconazole in treating murine C. glabrata vaginitis, with fluconazole requiring a higher dose to achieve similar efficacy 2.
- Another study from 1996 reported an overall efficacy of 77% for fluconazole in treating candidal infections caused by non-albicans Candida species, including C. glabrata, but noted that higher doses may be required for infections caused by C. glabrata 3.
- A 2025 study found that fluconazole step-down therapy was safe and reasonable in the management of C. glabrata candidaemia, with no significant difference in treatment duration or 30-day clinical failure compared to echinocandin therapy 6.
- Fluconazole is generally considered to be fungistatic against yeasts, including C. glabrata, and may not be effective against moulds or intrinsically resistant species like Candida krusei 4.
Factors Influencing Fluconazole Efficacy
- The susceptibility of C. glabrata isolates to fluconazole can vary, with some isolates exhibiting reduced susceptibility or resistance 2, 5.
- The dose and duration of fluconazole treatment may impact its effectiveness against C. glabrata, with higher doses or longer treatment durations potentially required for optimal efficacy 3, 4.
- The use of fluconazole as a step-down therapy after initial treatment with echinocandins may be a viable option for managing C. glabrata candidaemia 6.