Treatment of vaginitis caused by non-albicans Candida species.

INTRODUCTION: In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections. AREAS COVERED: In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients. EXPERT OPINION: We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.

Bacterial Vaginosis and Vulvovaginal Candidiasis Pathophysiologic Interrelationship.

Among the infectious causes of vulvovaginal symptoms, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) dominate. Apart from infrequent mixed infections, both are considered independent and caused by unrelated pathogenic mechanisms. Clinical experience, however, is strongly suggestive that in some populations these infections are linked with recurrent BV (RBV) serving as the dominant etiopathogenic trigger for development of recurrent VVC (RVVC) with profound clinical and therapeutic consequences. The biologic basis for this critical interrelationship is discussed and suggests that as a consequence of BV dysbiosis, and not necessarily because of antibiotics prescribed, immune defenses are compromised, neutralizing vaginal yeast tolerance. The consequent BV-induced vaginal proinflammatory environment predisposes to mixed infection or consecutive episodes of post-treatment VVC. Recurrent BV and repeated antimicrobial drug exposure also predispose to acquired fluconazole resistance in C. albicans isolates, contributing to refractory vulvovaginal candidiasis.

Recurrent Infectious Vaginitis: A Practical Approach for the Primary Care Clinician.

Recurrent infectious vaginitis can lead to significant morbidity, patient frustration, and health care costs. The most common causes are bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC); however, other infectious and noninfectious etiologies should be considered in patients with recurrent symptoms. A detailed history and physical examination with appropriate testing at the time of symptoms is critical to establishing a correct diagnosis. Management options for recurrent BV and VVC are limited. Complex cases including those with atypical symptoms, negative testing for common causes, refractory symptoms despite appropriate therapy or recurrences during suppressive therapy will require referral to specialist care.

Efficacy and Safety of Oteseconazole in Recurrent Vulvovaginal Candidiasis.

BACKGROUND: Management of recurrent vulvovaginal candidiasis (RVVC) is an unmet clinical challenge without approved treatment in the United States. Oteseconazole is a novel oral selective inhibitor of fungal CYP51, designed to treat RVVC without off-target toxicities. VIOLET comprised two global, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (CL-011 and CL-012). The primary objective was to evaluate oteseconazole efficacy through week 48. Key secondary objectives evaluated time to first recurrence, safety, and patient-reported outcomes. METHODS: Women with three or more symptomatic acute vulvovaginal candidiasis (VVC) episodes within the previous 12-month period, including the screening episode (in which the VVC episode cleared with fluconazole induction therapy), were randomly assigned 2:1 at baseline (maintenance phase) to 150 mg of oral oteseconazole daily for 7days and then once weekly for 11 weeks or to matching placebo for 12 weeks. Time-to-first-recurrence data were collected during the maintenance phase. Posttreatment follow-up was 36 weeks. RESULTS: Among 656 women (326 in CL-011 and 330 in CL-012), the averaged percentage of participants with one or more RVVC episodes through week 48 was 6.7% (range, 6.5 to 7.4%) in CL-011 and 3.9% (3.7 to 4.6%) in CL-012 in the oteseconazole groups versus 42.8% (41.3 to 45.0%) and 39.4% (38.0 to 42.6%) in the corresponding placebo groups (P<0.001). Among oteseconazole-treated participants in CL-011 and CL-012 who experienced an RVVC episode (n=22), the mean time to recurrence was 45.7 and 47.2 weeks versus 27.8 and 33.1 weeks for placebo-treated participants (n=84), respectively (hazard ratio [95% confidence interval], 0.11 [0.06 to 0.21] for CL-011 and 0.08 [0.04 to 0.17] for CL-012; P<0.001). Types and frequencies of treatment-emergent adverse events (TEAEs) were similar between groups in both trials, with no drug-related serious TEAEs or adverse effects on pregnancy outcomes, liver function, or QT interval. CONCLUSIONS: Oral oteseconazole was effective in preventing acute VVC recurrence and treating RVVC through week 48 in the CL-011 and CL-012 trials, with mostly mild TEAEs. (Funded by Mycovia Pharmaceuticals, Inc., ClinicalTrials.gov numbers, NCT03562156 for CL-011 and NCT03561701 for CL-012.)