A policy change could help lead to a rise in treatment-resistant vaginal thrush, amid a significant annual increase in the prevalence of fungal infections caused by the Candida fungal species, suggests the first study of its kind, published online in the magazine Sexually transmitted infections.
Although the exact reasons for these trends are not yet clear, they follow a shift in clinical practice aimed at reducing laboratory workload, the researchers say. Primary care family physicians are now encouraged to treat vaginal thrush empirically, based on signs and symptoms alone, rather than on the basis of confirmatory laboratory test results.
Vaginal thrush is common, with 3 in 4 women of childbearing age likely to be affected, researchers note. In approximately 1 in 10 women, these infections are recurrent, defined as at least 4 episodes in 12 months.
Resistance or lack of sensitivity to primary antifungal therapy (azoles) in Candida samples from patients with vaginal infection has been reported in other countries. This has also been seen in the UK, but only in specialist clinics, the researchers explain.
To get a more evidence-based picture of resistance levels and analyze wider trends, researchers examined culture results from 5,461 vaginal swabs previously collected from women with suspected complicated or recurrent yeast infections in Leeds, in the north of England, between April 2018 and March 2021.
About a third (1828; 33.5%) cultivated yeast, most of which (85%) was cultivated annually. Candida albicansthe fungus responsible for most cases of vaginal thrush.
But this proportion has declined each year due to an increase in other Candida species, the most common of which isolated was Nakaseomyces glabrataa species known to be less sensitive to azoles: this figure increased from just under 3% in 2018-19 to just under 7% in 2020-21. In total, the prevalence of these “other” species increased from 6% in 2018-2019 to more than 12.5% in 2020-2021.
Cultures were tested for sensitivity to treatment with antifungals, which showed that the prevalence of isolates resistant or less susceptible to fluconazole increased from 3.5% in 2018-2019 to almost 8% in 2019-2020 , and just over 9.5%. % in 2020-2021.
And the overall prevalence of fluconazole resistance increased from just under 1% in 2018-2019 to 1.5% in 2019-2020 and 3% in 2020-2021, a more than four-fold increase in three years.
Most fluconazole-insensitive isolates were either dose-sensitive or resistant to itraconazole (77% and 23%, respectively) and were also moderately or completely resistant to voriconazole (36.5% and 60%, respectively).
Most resistant isolates were Albicansand most of these cases were treated in primary care, although the proportion of resistant cases was higher in swab samples from specialist sexual health clinics in 2019-2020 and 2020-2021.
In 2020-2021, none of the yeasts from patients sampled in specialized sexual health clinics responded to fluconazole. No cases of overall resistance or reduced sensitivity were observed in hospitalized patients in 2018-2019 and 2019-2020, but some cases were observed in 2020-2021.
The study results confirm a significant increase in the prevalence of non-albicans and fluconazole-resistant Candida species. Albicans between 2018 and 2021, researchers estimate.
“This increase in (non-albicans) species is clinically concerning, as some have reduced intrinsic sensitivity to fluconazole,” they emphasize.
“Successful treatment of fluconazole-resistant diseases Albicans and species (non-albicans) can be very difficult, and it often requires multiple antifungal treatments. Many of these yeasts also had reduced sensitivity to itraconazole and voriconazole, further limiting treatment options,” they add.
“Since 2013, UK primary care guidelines (https://cks.nice.org.uk/topics/vaginal-discharge/) recommended that a clinical diagnosis of acute vulvovaginal candidiasis be made based on typical signs and symptoms… (with vaginal pH testing if available), followed by empiric treatment with a single dose of oral fluconazole or clotrimazole pessary”, explain the researchers.
“However, there is ample evidence that (vulvo-vaginal candidiasis) is overdiagnosed clinically by clinicians and patients, such that empiric treatment leads to inappropriate use of azoles,” they add.
They conclude: “The exact reasons for this increase (in fluconazole resistance) remain unclear, but it follows the introduction of restricted access to fungal cultures for the diagnosis of (vulvo-vaginal candidiasis) by workers in primary care.
“Clinical diagnosis, followed by empirical treatment, was recommended instead. Therefore, we believe that this policy of encouraging empirical treatment of vaginitis based on nonspecific symptoms and signs needs to be revisited.”
Source:
Journal reference:
Ratner, JC, et al. (2024). Increasing rate of non-Candida albicansyeast and fluconazole resistance in yeast isolates from women with recurrent vulvovaginal candidiasis in Leeds, UK. Sexually transmitted infections. doi.org/10.1136/sextrans-2024-056186.