Candida glabrata (Nakaseomyces glabrata) Vulvovaginal Candidiasis in Pregnancy

Why C. glabrata is a special problem

1. Intrinsic azole resistance - it does not form pseudohyphae, is not visible on routine KOH microscopy, and has reduced susceptibility to the standard azole antifungals used in pregnancy (clotrimazole, miconazole). Culture with species identification is therefore essential.
2. Limited safe options in pregnancy - the most effective agents for C. glabrata (oral fluconazole, boric acid, flucytosine) are either contraindicated or carry significant safety concerns in pregnancy.

Diagnosis

• Vaginal culture or PCR is mandatory - C. glabrata is not recognized on routine microscopy (no pseudohyphae/hyphae). Culture and susceptibility testing should be done for any woman who remains symptomatic after standard azole treatment.
• Consider mixed infection: prevalence of mixed vaginal infections is 6.5-61% during pregnancy vs. 2.4-10% in non-pregnant women.

Treatment Options in Pregnancy

First-line: Topical Azoles (7 days)

Nystatin - Key option for C. glabrata in pregnancy

• Recommended dose in pregnancy: 100,000 IU intravaginally once daily for 14 days
• It is FDA Category A for topical/vaginal use - no systemic absorption
• European guidelines list nystatin as first-line for chronic VVC due to C. glabrata
• Nystatin is effective against all Candida species including azole-resistant strains, making it the preferred agent when C. glabrata is identified in pregnancy

Oral Fluconazole - CONTRAINDICATED

• Single 150 mg dose is associated with spontaneous abortion and congenital anomalies (cardiac defects, limb reduction) at higher doses
• Should not be used regardless of the Candida species

Boric Acid - Generally Avoided in Pregnancy

• Boric acid 600 mg vaginal suppositories are used for non-albicans VVC/C. glabrata in non-pregnant women (70% eradication rate at 3 weeks)
• NOT recommended in pregnancy - boric acid is a teratogen and is systemically absorbed in small amounts; it is contraindicated
• This is a key limitation: one of the most effective non-azole options for C. glabrata cannot be used

Practical Management Algorithm in Pregnancy

C. glabrata confirmed on culture in pregnancy
│
├── Symptomatic?
│   ├── YES → Treat (untreated VVC risks preterm labor, low birth weight, neonatal candidiasis)
│   └── NO (asymptomatic colonization) → Treatment debated; some guidelines recommend treatment in 3rd trimester to reduce neonatal risk
│
└── Treatment choice:
    1. Nystatin 100,000 IU vaginally x 14 days (preferred - FDA Cat A, effective vs. glabrata)
    2. Topical azole (clotrimazole/miconazole) x 7-14 days (less effective vs. glabrata but safe)
    3. If no response → Specialist referral
    ✗ Oral fluconazole → CONTRAINDICATED
    ✗ Boric acid → CONTRAINDICATED in pregnancy
    ✗ Topical flucytosine → No established safety data in pregnancy

Additional Considerations

• Recurrence is common in pregnancy due to high estrogen levels promoting vaginal glycogen, lowering pH, and increasing Candida colonization
• Probiotics (lactobacillus-based) may be considered adjunctively but evidence is insufficient for a definitive recommendation
• Trimester matters: extra caution is warranted in the first trimester; any systemic exposure should be avoided
• After delivery, if the infection persists, boric acid 600 mg vaginal suppositories x 14-21 days and/or topical flucytosine (17.5 mg/mL cream) can be used as more definitive C. glabrata therapy

Clinical note: Because C. glabrata is intrinsically azole-resistant and the most effective alternatives (boric acid, flucytosine, echinocandins) cannot be used in pregnancy, nystatin 100,000 IU vaginally x 14 days is the most rational and safe first-line option. Specialist involvement (MFM or infectious disease) is advised for refractory or recurrent cases in pregnancy.