# Therapeutic Tools for Vulvovaginal Candidiasis: Current and Emerging Antifungal Agents

**Authors:** Guillermo Quindós, Iker De-la-Pinta, Cristina Marcos-Arias, Nerea Jauregizar, Elena Sevillano, Lucila Madariaga, Elena Eraso

PMC · DOI: 10.3390/jof12020152 · 2026-02-20

## TL;DR

This review discusses current and new treatments for vulvovaginal candidiasis, a common fungal infection, focusing on addressing drug resistance and improving therapeutic options.

## Contribution

The paper introduces novel antifungal agents like ibrexafungerp and oteseconazole with new mechanisms of action for resistant cases.

## Key findings

- Azole-resistant non-Candida albicans species are complicating VVC treatment.
- Ibrexafungerp and oteseconazole show promise as new therapeutic options for resistant infections.
- Emerging approaches like mucoadhesive formulations and immunomodulation are being explored.

## Abstract

Vulvovaginal candidiasis (VVC) represents a widespread gynaecological challenge, affecting approximately 75% of women at some point during their reproductive years, with a significant subset progressing to recurrent forms (RVVC). Classical azoles and polyenes remain the cornerstone of therapy. However, their clinical utility is undermined by the rise of azole-resistant non-Candida albicans species, the capacity of Candida to form biofilms, and a complex variety of host-related factors that complicate disease expression and therapeutic response. This narrative review provides a critical up-to-date examination of the therapeutic landscape, integrating current diagnostic algorithms with pharmacological strategies for both acute, recalcitrant and recurrent VVCs. We assess the efficacy and safety of established antifungal agents alongside the breakthrough introduction of novel drug classes, with a particular interest in the oral triterpenoid ibrexafungerp and the tetrazole oteseconazole, which offer new mechanisms of action for cases that fail to respond to standard regimens. Furthermore, we address the management of a special clinical scenarios, including pregnancy and lactation, and explore promising emerging innovative approaches such as mucoadhesive formulations, immunomodulatory approaches, and alternative non-antifungal therapies. Ultimately, this review aims to support clinical decision-making by balancing the accessibility and user-friendliness of conventional treatments with the targeted precision offered by modern antifungal agents.

## Linked entities

- **Chemicals:** ibrexafungerp (PubChem CID 46871657), oteseconazole (PubChem CID 77050711)
- **Diseases:** vulvovaginal candidiasis (MONDO:0006014)
- **Species:** Candida (taxon 5475)

## Full-text entities

- **Genes:** CYP2C8 (cytochrome P450 family 2 subfamily C member 8) [NCBI Gene 1558] {aka CPC8, CYP2C8DM, CYPIIC8, MP-12/MP-20}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, CYP51A1 (cytochrome P450 family 51 subfamily A member 1) [NCBI Gene 1595] {aka CP51, CYP51, CYPL1, LDM, P450-14DM, P450L1}, ALS3 (amyotrophic lateral sclerosis 3 (autosomal dominant)) [NCBI Gene 253] {aka ALS6}, ELK3 (ETS transcription factor ELK3) [NCBI Gene 2004] {aka ERP, NET, SAP-2, SAP2}, CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}
- **Diseases:** nausea (MESH:D009325), medical (MESH:D000069279), diarrhoea (MESH:D003967), metabolic disorders (MESH:D008659), pruritus (MESH:D011537), vomiting (MESH:D014839), headache (MESH:D006261), inflammatory (MESH:D007249), gastrointestinal symptoms (MESH:D012817), injury to (MESH:D014947), bacterial vaginosis (MESH:D016585), congenital malformations (OMIM:163000), irritation (MESH:D001523), diabetes mellitus (MESH:D003920), vaginal dysbiosis (MESH:D064806), abdominal pain (MESH:D015746), mucositis (MESH:D052016), Candidiasis (MESH:D002177), allergic reactions (MESH:D004342), Vaginitis (MESH:D014627), fungal (MESH:D009181), QT prolongation (MESH:D008133), erythema (MESH:D004890), genital infectious diseases (MESH:D003141), vulvovaginal dermatoses (MESH:D014848), immunodeficiencies (MESH:D007153), trichomoniasis (MESH:D014245), genital infections (MESH:D007239), gastrointestinal (MESH:D005767), abortion (MESH:D000026), immune dysfunction (MESH:D007154), toxicity (MESH:D064420), AVVC (MESH:D002181)
- **Chemicals:** 5-FU (MESH:D005472), imidazole (MESH:C029899), tetrazoles (MESH:D013777), fenticonazole (MESH:C033486), miconazole (MESH:D008825), isoconazole (MESH:C020382), eberconazole (MESH:C118963), diclofenac (MESH:D004008), imidazoles (MESH:D007093), methylene blue (MESH:D008751), glycogen (MESH:D006003), rezafungin (MESH:C000629634), posaconazole (MESH:C101425), Clotrimazole (MESH:D003022), essential oils (MESH:D009822), chlorhexidine (MESH:D002710), Sertaconazole (MESH:C061131), tetrazole (MESH:C045574), acetic acid (MESH:D019342), Echinocandins (MESH:D054714), Voriconazole (MESH:D065819), econazole (MESH:D004464), Oteseconazole (MESH:C000599187), oxiconazole (MESH:C022155), antimicrobial peptides (MESH:D000089882), 5-fluorocytosine (MESH:D005437), ciclopirox olamine (MESH:D000077768), micafungin (MESH:D000077551), lactic acid (MESH:D019344), butoconazole (MESH:C017125), boric acid (MESH:C032688), selenium sulphide (MESH:C025698), Azoles (MESH:D001393), Fluconazole (MESH:D015725), triazoles (MESH:D014230), itraconazole (MESH:D017964), Polyenes (MESH:D011090), tea tree oil (MESH:D020947), sulconazole (MESH:C033308), KOH (MESH:C029943), Nystatin (MESH:D009761), Ibrexafungerp (MESH:C569338), bifonazole (MESH:C036596), caffeic acid (MESH:C040048), caspofungin (MESH:D000077336), povidone-iodine (MESH:D011206), terbinafine (MESH:D000077291), albaconazole (MESH:C112424), 5-FUTP (-), lidocaine (MESH:D008012), gentian violet (MESH:D005840), anidulafungin (MESH:D000077612), flutrimazole (MESH:C076986), tioconazole (MESH:C020527), Isavuconazole (MESH:C508735), Amphotericin B (MESH:D000666), omoconazole (MESH:C050566), propolis (MESH:D011429), ergosterol (MESH:D004875), terconazole (MESH:C037815)
- **Species:** Gardnerella vaginalis (species) [taxon 2702], Limosilactobacillus vaginalis (species) [taxon 1633], Allium sativum (garlic, species) [taxon 4682], Candida albicans (species) [taxon 5476], Candida tropicalis (species) [taxon 5482], Pichia kudriavzevii (species) [taxon 4909], Nakaseomyces glabratus (species) [taxon 5478], Candidozyma auris (species) [taxon 498019], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Lodderomyces metapsilosis (species) [taxon 273372], Nakaseomyces nivariensis (species) [taxon 418086], Nakaseomyces bracarensis (species) [taxon 273131], Lodderomyces orthopsilosis (species) [taxon 273371], Candida africana (species) [taxon 241526], Meyerozyma guilliermondii (species) [taxon 4929], Lodderomyces parapsilosis (species) [taxon 5480], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941849/full.md

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Source: https://tomesphere.com/paper/PMC12941849