# Vaginal chlorhexidine gluconate versus fluconazole for recurrent vulvovaginal candidiasis: A randomized noninferiority trial

**Authors:** Cathrin Alvendal, Tyra Hasselrot, Margaux Balduck, Gabriella Edfeldt, Ina Schuppe-Koistinen, Annelie Brauner, Daniel Altman, Kristina Broliden, Nina Bohm-Starke

PMC · DOI: 10.1371/journal.pone.0340862 · PLOS One · 2026-01-20

## TL;DR

A study compared a new treatment for recurring yeast infections with the standard drug, finding similar effectiveness but more irritation with the new treatment.

## Contribution

The study evaluates a new treatment option for yeast infections that could address drug resistance concerns.

## Key findings

- CHG showed comparable efficacy to FLZ in clearing C. albicans infections.
- FLZ promoted Lactobacillus crispatus dominance, unlike CHG.
- 16% of C. albicans isolates showed reduced susceptibility or resistance to FLZ.

## Abstract

Recurrent vulvovaginal candidiasis (RVVC) is a common condition characterized by frequent relapses, often without a clearly identifiable cause. Fluconazole (FLZ) is the standard treatment but concerns about emerging resistance and drug interaction highlight the need for alternative therapies. Chlorhexidine gluconate (CHG), known for its antifungal and biofilm-disrupting properties, has been proposed as a potential alternative.

To evaluate the efficacy, tolerability, and microbiome impact of a vaginal CHG formulation compared to oral FLZ in the treatment of RVVC caused by Candida albicans.

An open label randomized non-inferiority trial was conducted to compare vaginal CHG and FLZ treatments. Primary outcome was negative cultures for C. albicans. Resistance profiles and changes in the vaginal microbiome composition were also assessed.

The study was terminated early due to local irritation associated with CHG and the study design was transitioned into a pilot study. CHG treatment showed comparable efficacy to FLZ in clearing C. albicans infections and preventing recurrences, although the sample size was limited. All 11 participants in the FLZ group cleared the infection after one week treatment, compared to 9 out 11 in the CHG group. No harmful changes to the vaginal microbiome were observed in the CGH or FLZ group. FLZ promoted a shift toward Lactobacillus crispatus dominance, unlike CHG. Notably, 16% of C. albicans isolates exhibited reduced susceptibility or resistance to FLZ.

Due to the limited number of participants, we cannot conclusively determine whether CHG is non-inferior to FLZ in terms of efficacy for clearing acute C. albicans infections or preventing recurrences. While the current CHG formulation caused local irritation and is not suitable for clinical use, its antifungal and biofilm-inhibiting properties remain promising. Further development of less irritative CHG formulations may offer a valuable alternative for RVVC treatment, particularly in the context of rising FLZ resistance.

## Linked entities

- **Chemicals:** chlorhexidine gluconate (PubChem CID 9552081), fluconazole (PubChem CID 3365)

## Full-text entities

- **Diseases:** C. albicans infections (MESH:D007239), irritation (MESH:D001523), RVVC (MESH:D002181)
- **Chemicals:** FLZ (MESH:D015725), CHG (MESH:C010882)
- **Species:** Candida albicans (species) [taxon 5476], Lactobacillus crispatus (species) [taxon 47770]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12818662/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12818662/full.md

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Source: https://tomesphere.com/paper/PMC12818662