Ciclopirox olamine against vulval mycosis?

Vulvar mycoses are among the most common infections of the female genital region. They are generally caused by yeasts of the genus Candida, of which Candida albicans is the predominant species. Naturally present in the vaginal flora, this yeast can become pathogenic when an imbalance of the microbiota or a local change in pH promotes its proliferation. Vulvar candidiasis episodes manifest as itching, burning sensations, redness and sometimes thick whitish discharge. Although most infections are mild and transient, they remain painful and disruptive to daily life.

Vulvar fungal infections require medical management, whether by consulting a general practitioner or seeking advice from a pharmacist.

In most cases, an antifungal cream is prescribed for application to the intimate area until symptoms resolve. Among the most commonly used active agents are imidazoles such as econazole or isoconazole, but also the ciclopirox olamine. The latter is a well-established antifungal, capable of acting against a broad spectrum of fungi, including yeasts of the genus Candida. An in vitro study demonstrated the inhibitory effect of ciclopirox olamine on Candida albicans. Different doses were added to the culture medium, and researchers observed that microbial growth decreased progressively with higher concentrations of ciclopirox olamine.

After exposing fungal cells to a concentration of 0.6 µg/mL of ciclopirox olamine, the researchers analysed the expression of 47 genes known for their role in iron metabolism and drug resistance. The results show that ciclopirox induces a strong upregulation of genes related to iron metabolism (FTR1, FTR2, FTH1, CCC2, CFL1 and SIT1) and a state close to that of deficiency. The addition of ferric chloride (FeCl₃) to the medium actually reversed these effects, confirming that ciclopirox’s action relies largely on a iron chelation, an essential metal for fungal enzymatic activity.

The study also revealed that, despite a slight induction of the resistance genes CDR1 and CDR2, no development of tolerance or resistance was observed, even after six months of continuous exposure to ciclopirox olamine. This stability contrasts with observations made under fluconazole, where an increase in minimum inhibitory concentrations was recorded after just two months. Moreover, although the serum-induced yeast-to-hypha morphological transition remains unaffected, ciclopirox olamine-treated cells display increased sensitivity to oxidative stress, notably to hydrogen peroxide, a reactive oxygen species derivative. This vulnerability suggests a dysfunction of iron-dependent enzymes involved in the detoxification of reactive oxygen species.

This antifungal activity of ciclopirox olamine against yeasts of the genus Candida explains why it is frequently used to treat vulvovaginal fungal infections.

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