What is the recommended treatment for Candida glabrata infections?

Treatment of Candida glabrata Infections

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line therapy for Candida glabrata infections, particularly for candidemia and invasive disease. 1

Initial Therapy Selection

Echinocandins as First-Line Treatment

• Echinocandins are strongly preferred for C. glabrata infections due to this species' intrinsic reduced susceptibility to azole antifungals, particularly fluconazole. 1

• The three echinocandin options with equivalent efficacy include:

  • Caspofungin: 70 mg loading dose, then 50 mg daily 1
  • Micafungin: 100 mg daily 1
  • Anidulafungin: 200 mg loading dose, then 100 mg daily 1

• This recommendation applies to moderately severe to severe illness, recent azole exposure, and specifically when C. glabrata is identified or suspected. 1

When Fluconazole Should NOT Be Used

• Fluconazole monotherapy should be avoided for confirmed C. glabrata infections due to high intrinsic resistance rates and frequent treatment failures. 1, 2, 3

• Transition from an echinocandin to fluconazole is not recommended without confirmation of isolate susceptibility through formal antifungal susceptibility testing. 1

• Even when susceptibility is confirmed, fluconazole step-down should only occur after clinical stability is achieved and blood cultures have cleared. 1, 4

Alternative Therapies

Amphotericin B Formulations

• Amphotericin B deoxycholate (0.5-1.0 mg/kg daily) or lipid formulations (3-5 mg/kg daily) are acceptable alternatives when echinocandins cannot be used due to intolerance or limited availability. 1

• Amphotericin B can be combined with oral flucytosine (25 mg/kg four times daily) for enhanced activity, particularly in fluconazole-resistant strains. 3

Voriconazole

• Voriconazole (400 mg twice daily for 2 doses, then 200 mg twice daily) is reserved for step-down oral therapy in selected cases of voriconazole-susceptible C. glabrata after clinical stability is achieved. 1

• The FDA label confirms voriconazole showed 33% success rates for C. glabrata candidemia, which is lower than for other Candida species. 5

Treatment Duration and Monitoring

Duration of Therapy

• Continue treatment for 2 weeks after documented clearance of Candida from the bloodstream AND resolution of all symptoms attributable to candidemia. 1

• Perform follow-up blood cultures daily or every other day until clearance is documented. 1

Essential Adjunctive Measures

• Remove intravenous catheters as early as possible in nonneutropenic patients with candidemia—this is strongly recommended and critical for treatment success. 1

• Perform dilated ophthalmological examination within the first week after diagnosis in all nonneutropenic patients to evaluate for endophthalmitis. 1

• Evaluate for and address any metastatic complications including endocarditis, which occurs more frequently with C. glabrata. 1

Site-Specific Considerations

Vulvovaginal Candidiasis

• Topical intravaginal boric acid 600 mg daily for 14 days is first-line therapy for C. glabrata vulvovaginitis, especially when oral azoles have failed. 2

• Alternative options include nystatin intravaginal suppositories (100,000 units daily for 14 days) or topical 17% flucytosine cream with or without 3% amphotericin B cream for 14 days. 2

• Standard azole therapies (fluconazole, itraconazole) frequently fail due to intrinsic resistance. 2, 6

Respiratory Colonization

• C. glabrata isolated from sputum represents colonization, not infection, and does not require antifungal treatment in the absence of documented invasive disease. 3

• True Candida pneumonia is extremely rare and requires tissue biopsy showing invasion for confirmation before treatment. 3

• Treating sputum colonization leads to unnecessary antifungal exposure, promotes resistance, and causes avoidable adverse effects. 3

Critical Pitfalls to Avoid

Common Treatment Errors

• Never use fluconazole empirically for suspected C. glabrata infections without documented susceptibility—this is a frequent cause of treatment failure. 1, 3

• Do not assume echinocandin susceptibility is universal—while rare, echinocandin resistance in C. glabrata is emerging and requires higher dosages in neutropenic hosts for fungicidal activity. 7

• Avoid premature step-down to oral azoles before confirming clinical stability, negative blood cultures, and documented azole susceptibility. 1

Special Population Considerations

• In neutropenic patients, standard echinocandin dosages may only achieve fungistatic effects—higher dosages may be required for fungicidal activity, though specific recommendations await further clinical validation. 7

• For neonates with disseminated C. glabrata infection, amphotericin B deoxycholate is preferred due to lack of pharmacokinetic data for echinocandins in this population. 8

Emerging Therapies

• Ibrexafungerp, a novel oral glucan synthase inhibitor, demonstrates broad activity against wild-type, azole-resistant, and echinocandin-resistant C. glabrata in preclinical studies, representing a promising future option for resistant infections. 9