Impact of vaginal microbiota on the clinical efficacy and long-term recurrence of ketoconazole suppositories in treating severe vulvovaginal candidiasis: a secondary analysis of a multicentre randomised trial.

OBJECTIVE

To evaluate whether baseline vaginal-microbiota status influences the clinical cure rate and 30-day mycological recurrence of severe VVC after 6-day intravaginal ketoconazole therapy compared with miconazole nitrate.

METHODS

A prospective, randomized, positive drug-controlled, multicenter clinical study was conducted from April 2022 to October 2023 across nine hospitals in China. A total of 253 patients diagnosed with severe vulvovaginal candidiasis were enrolled. The study group received ketoconazole suppositories, while the control group received miconazole nitrate vaginal capsules. Vaginal microbiota results were recorded at enrollment, and follow-up assessments were conducted at 10 and 30 days post-treatment to evaluate the relationship between vaginal microbiota and treatment efficacy and recurrence rates.Vaginal microbiota was categorised by Gram-stain microscopy into (i) normal flora (Lactobacillus spp. dominant), (ii) BV-associated abnormal flora (Gram-variable short rods dominant) and (iii) non-BV abnormal flora (other morphotypes).

RESULTS

At enrollment, there were no significant differences between the study and control groups in terms of symptom and sign scores, vaginal dominant bacteria. At the 10-day follow-up, the clinical efficacy rates for patients with normal and abnormal vaginal microbiota were 86.7% and 75.5%, respectively, with a statistically significant difference (P = 0.021). In the study group, the clinical efficacy rates for patients with normal flora, BV-associated abnormal flora, and non-BV-associated abnormal flora were 89.2%, 79.2%, and 78.9%, respectively, with no significant difference (P = 0.264). In the control group, the clinical efficacy rates for patients with normal flora, BV-associated abnormal-flora, and non-BV-associated abnormal flora were 84.1%, 86.7%, and 63.6%, respectively, with a significant difference (P = 0.045).Among the 253 patients, 198 patients who achieved clinical cure and mycological negativity after initial treatment and had mycological follow-up results at 30 days were analyzed. The proportion of mycological positivity at the 30-day follow-up was 14.8% (16/108) in the study group and 26.7% (24/90) in the control group, with a statistically significant difference in recurrence rates between the two groups (P = 0.039). Among the 126 patients with normal dominant bacteria at enrollment,the proportion of mycological positivity at the 30-day follow-up was 12.3% (8/65) in the study group and 26.2% (16/61) in the control group, with a statistically significant difference in recurrence rates (P = 0.047).

CONCLUSION

The vaginal microbiota, particularly the dominant bacteria, may influence treatment efficacy and recurrence rates. In the treatment of severe vulvovaginal candidiasis, ketoconazole suppositories are not inferior to miconazole nitrate vaginal capsules in clinical efficacy and have a lower long-term recurrence rate.