Policy change linked to rise in treatment-resistant vaginal thrush

A change in policy may be helping to drive a rise in treatment-resistant vaginal thrush, amid significant yearly increases in the prevalence of fungal infections caused by fungal Candida species, suggests the first study of its kind, published online in the journal Sexually Transmitted Infections.

While the exact reasons for these trends aren't yet clear, they follow a shift in clinical practice, with the aim of reducing laboratory workload, say the researchers. Family doctors in primary care are now encouraged to treat vaginal thrush empirically – on signs and symptoms alone, rather than on confirmatory lab test results.

Vaginal thrush is common, with 3 in every 4 women of reproductive age likely to be affected, note the researchers. In around 1 in 10 women these infections are recurrent – defined as at least 4 episodes within 12 months. 

Resistance or lack of sensitivity to the mainstay of antifungal treatment (azoles) in Candida specimens from patients with a vaginal infection has been reported in other countries. This has also been noted in the UK, but only in specialist clinics, explain the researchers.

To obtain a more evidence based picture of resistance levels and analyse wider trends, the researchers reviewed the culture results of 5461 vaginal swabs previously taken from women with suspected complicated or recurrent yeast infection in Leeds, northern England, between April 2018 and March 2021.

Around a third (1828; 33.5%) grew yeasts, most of which (85%) every year were Candida albicans, the fungus responsible for most cases of vaginal thrush. 

But this proportion declined yearly amid an increase in other Candida species, of which the most common one isolated was Nakaseomyces glabrata, a species known to be less susceptible to azoles: this increased from just under 3% in 2018–19 to just under 7% in 2020–21. In all, the prevalence of these 'other' species increased from 6% in 2018–19 to 12.5%+ in 2020–21. 

The cultures were tested for their susceptibility to treat with antifungals, and this showed that the prevalence of isolates resistant, or less susceptible, to fluconazole rose from 3.5% in 2018–19 to almost 8% in 2019–20, and to just over 9.5% in 2020–21. 

And the overall prevalence of fluconazole resistance increased from just under 1% in 2018–19, to 1.5% in 2019–20, and to 3% in 2020–21 – a more than fourfold increase over the 3 years.

Most of the isolates unresponsive to fluconazole were either sensitive according to dose or resistant to itraconazole (77% and 23%, respectively) and were also moderately or fully resistant to voriconazole (36.5% and 60%, respectively). 

Most of the resistant isolates were C albicans, and most of these cases were dealt with in primary care, although the proportion of resistant cases was higher in the swab samples from specialist sexual health clinics in 2019–20 and 2020–21. 

In 2020–21, none of the yeasts from patients sampled at specialist sexual health clinics responded to fluconazole. No cases of overall resistance or reduced susceptibility were seen in hospital patients in 2018–19 and 2019–20, but some cases were seen in 2020–21.

The study findings confirm a significant increase in the prevalence of non-albicans Candida species and fluconazole-resistant C albicans between 2018 and 2021, say the researchers. 

"This increase in [non-albicans] species is of clinical concern as some have intrinsic reduced susceptibility to fluconazole," they highlight.

"Successful treatment of fluconazole-resistant C albicans and [non-albicans] species can be very challenging, and this frequently requires multiple courses of antifungal treatment. Many of these yeasts also had reduced sensitivity to itraconazole and voriconazole, limiting treatment options even further," they add.

"Since 2013, UK primary care guidance (https://cks.nice.org.uk/topics/vaginal-discharge/) has recommended a clinical diagnosis of acute [vulvovaginal candidiasis] be made based on the typical signs and symptoms…(with testing for vaginal pH if available), followed by empirical treatment with single dose oral fluconazole or clotrimazole pessary," explain the researchers.

"However, there is considerable evidence that [vulvovaginal candidiasis] is over diagnosed clinically by both clinicians and patients, so empirical treatment leads to inappropriate azole use," 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 [vulvovaginal candidiasis] by those working in primary care. 

"A clinical diagnosis, followed by empirical treatment, has been recommended instead. Consequently, we believe this policy of encouraging empirical vaginitis treatment based on non-specific symptoms and signs needs revisiting."