What is the treatment for Nakaseomyces glabrata infection in an immunocompromised patient?

Treatment of Nakaseomyces glabrata in Immunocompromised Patients

For invasive N. glabrata infections in immunocompromised patients, echinocandins (caspofungin, micafungin, or anidulafungin) are the preferred first-line agents due to this organism's intrinsic reduced susceptibility to azoles. 1

Primary Treatment Recommendations

First-Line Therapy: Echinocandins

• Caspofungin: 70 mg loading dose, then 50 mg daily IV 2
• Micafungin: 100 mg daily IV 2
• Anidulafungin: 200 mg loading dose, then 100 mg daily IV 2

These agents are strongly preferred because N. glabrata demonstrates intrinsic reduced susceptibility to all azole antifungals, including fluconazole and voriconazole 1, 3. Recent European data shows 10.47% fluconazole resistance and 14.45% voriconazole resistance among N. glabrata isolates 4.

Alternative Therapy When Echinocandins Cannot Be Used

• Amphotericin B deoxycholate: 0.6-1.0 mg/kg daily IV 2
• For severe infections: 0.7 mg/kg daily, with or without oral flucytosine (25 mg/kg four times daily) 1

Amphotericin B demonstrates high sensitivity against N. glabrata isolates and serves as a reliable alternative 4.

Critical Clinical Considerations

Why Fluconazole Should Be Avoided

• Do not use empirical fluconazole for suspected invasive N. glabrata due to high resistance rates 1
• Even high-dose fluconazole (800 mg/day) is unreliable for this species 2
• Many authorities prefer amphotericin B over fluconazole even when susceptibility testing suggests potential activity 2

Emerging Resistance Patterns

• Approximately 10% of clinical N. glabrata isolates now display co-resistance to both azoles and echinocandins 5
• European surveillance shows 0.89% resistance to anidulafungin among echinocandins 4
• Echinocandin resistance is associated with FKS2 gene mutations (particularly R1377K substitution in hotspot 2 region) 6

Site-Specific Treatment Modifications

Candidemia/Bloodstream Infections

• Initiate echinocandin therapy immediately upon identification of N. glabrata 2, 1
• Remove central venous catheters when feasible 2
• Continue treatment for 2 weeks after documented clearance of bloodstream and resolution of symptoms 2

Mucosal Infections (Oropharyngeal/Esophageal)

• Topical therapy: Nystatin suspension (100,000 U/mL, 4-6 mL four times daily) for 7-14 days 3
• Refractory cases: Consider systemic echinocandin therapy 2
• N. glabrata is increasingly recognized as a cause of azole-refractory mucosal candidiasis, particularly in patients with advanced immunosuppression 2

Vulvovaginal Infections

• First-line: Topical intravaginal boric acid 600 mg daily for 14 days 1
• Second-line: Nystatin intravaginal suppositories 100,000 units daily for 14 days 1, 3
• Third-line: 17% flucytosine cream alone or combined with 3% amphotericin B cream daily for 14 days 1

Essential Management Principles

Immune Reconstitution

• Successful treatment requires reconstitution of the host immune system when possible 2
• Outcome is closely related to the degree and persistence of immunosuppression 2

Antifungal Susceptibility Testing

• Always obtain susceptibility testing to guide definitive therapy 4, 6
• This is particularly critical given rising echinocandin resistance rates 4, 5
• Be aware that broth microdilution methodologies for caspofungin show high inter-laboratory variation; consider using micafungin as a sentinel echinocandin for testing 7

Duration of Therapy

• Continue treatment until clinical resolution and clearance of infection 2
• For candidemia: minimum 2 weeks after blood culture clearance 2
• For deep-seated infections: may require weeks to months depending on site and immune status 2

Common Pitfalls to Avoid

• Never assume azole susceptibility without testing—N. glabrata has intrinsic reduced azole susceptibility 1, 3
• Do not rely on fluconazole as empirical therapy even in less critically ill patients 1
• Avoid suboptimal dosing—South African data shows 54% of N. glabrata candidemia patients received only fluconazole, most at suboptimal doses 6
• Do not delay echinocandin therapy while awaiting susceptibility results in invasive disease 1