What is the recommended treatment for recurrent vaginal Candida glabrata infection in a patient with myeloperoxidase (MPO) deficiency?

Treatment of Recurrent Vaginal Candida glabrata Infection in Myeloperoxidase Deficient Patients

For recurrent vaginal Candida glabrata infection in a myeloperoxidase (MPO) deficient patient, initiate topical intravaginal boric acid 600 mg daily for 14 days as first-line therapy, followed by consideration of long-term suppressive therapy given the dual challenge of azole-resistant organism and impaired neutrophil killing capacity. 1, 2

Understanding the Clinical Challenge

This scenario presents a particularly difficult therapeutic problem combining two distinct challenges:

• C. glabrata demonstrates inherent reduced susceptibility to azole antifungals, with therapy frequently failing even in immunocompetent hosts 1, 3
• MPO deficiency impairs the neutrophil oxidative burst mechanism, reducing the ability to kill Candida organisms even when antifungal therapy suppresses fungal growth [@general medical knowledge@]
• The combination creates a "perfect storm" where both pharmacologic therapy is less effective AND host defenses are compromised 3, 4

First-Line Treatment Approach

Boric acid remains the cornerstone of C. glabrata vulvovaginitis treatment:

• Administer 600 mg intravaginal boric acid in gelatin capsule daily for 14 days 1, 2
• This achieves approximately 70% eradication rates even in azole-unresponsive cases 5
• The IDSA provides this as a strong recommendation despite low-quality evidence, reflecting clinical consensus on its superiority for this indication 1

Alternative Treatment Options if Boric Acid Fails

If boric acid therapy is unsuccessful or not tolerated, consider these sequential alternatives:

• Second-line: Nystatin 100,000 units intravaginal suppository daily for 14 days 1, 2
• Third-line: Topical 17% flucytosine cream alone or combined with 3% amphotericin B cream daily for 14 days (requires compounding pharmacy) 1
• Investigational option: Voriconazole 200 mg orally every 12 hours for 14 days has shown efficacy in small case series of fluconazole-resistant C. glabrata 6, though this is not guideline-recommended

Critical Pitfall: Avoid Fluconazole Monotherapy

• Standard fluconazole regimens (150 mg weekly) that work for C. albicans recurrent VVC are ineffective for C. glabrata 1, 2
• Azole therapy for C. glabrata frequently fails and can select for further resistance 3, 4
• The 2016 IDSA guidelines explicitly state that azole therapy is "frequently unsuccessful" for C. glabrata VVC 1

Long-Term Suppressive Strategy

Given the MPO deficiency creating persistent vulnerability, consider maintenance therapy after achieving initial cure:

• No specific guidelines exist for suppressive therapy in C. glabrata VVC with immunodeficiency [@general medical knowledge@]
• Extrapolating from recurrent VVC management, consider intermittent boric acid suppositories (e.g., twice weekly) after successful induction, though this is not evidence-based 5
• Monthly follow-up during the first 3-6 months to detect early recurrence is prudent 7

Diagnostic Confirmation Requirements

Before and during treatment:

• Obtain vaginal cultures to confirm C. glabrata species identification, as microscopy alone cannot reliably distinguish it from other Candida species 1, 2
• C. glabrata does not form pseudohyphae or hyphae, making microscopic recognition difficult 2
• Verify normal vaginal pH (4.0-4.5) to exclude bacterial vaginosis or other mixed infections 1

Addressing Underlying Host Factors

In MPO-deficient patients specifically:

• Screen for diabetes mellitus, as this compounds the immune dysfunction and requires extended therapy courses 5
• Assess for other immunosuppressive conditions (HIV, corticosteroid use) that may require systemic antifungal approaches 5
• Recognize that MPO deficiency alone, while impairing fungal killing, does not typically cause severe systemic candidiasis but does predispose to recurrent mucosal infections [@general medical knowledge@]

Emerging Therapeutic Option

• Ibrexafungerp, a novel oral triterpenoid antifungal FDA-approved in 2021 for VVC and 2022 for recurrent VVC, demonstrates activity against azole-resistant C. glabrata 8, 9
• It achieves 9-fold higher concentrations in vaginal tissue versus plasma and maintains efficacy in low pH environments 8, 9
• This represents a potential future option for refractory cases, though cost and availability may limit current use 8

Monitoring Treatment Response

• Evaluate clinical response after completing the 14-day treatment course 2
• Obtain repeat vaginal cultures 1 month post-treatment to document mycological cure 7
• Instruct the patient to return immediately if symptoms recur within 2 months, as this suggests treatment failure requiring alternative therapy 7, 2

Special Counseling Points

• Advise that oil-based boric acid capsules and other vaginal preparations may weaken latex condoms and diaphragms 2
• Emphasize completing the full 14-day course even if symptoms resolve earlier, as premature discontinuation increases recurrence risk 2
• Set realistic expectations: C. glabrata infections are more difficult to eradicate than C. albicans, and recurrence rates are higher even with optimal therapy 3