Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid.

OBJECTIVE: The authors investigate the incidence of clinical and mycological resistance of Candida albicans vulvovaginitis (VVC) at the Jefferson Vulvovaginal Health Center. They also review their experience with boric acid in the treatment of fluconazole-resistant VVC. METHODS: The authors conducted a retrospective chart review of all patients with C. albicans VVC diagnosed at the Jefferson Vulvovaginal Health Center between November 2019 and December 2021. Patients with clinically defined fluconazole resistance were identified. Information about demographics, in vitro susceptibility testing, and treatment outcomes with boric acid was obtained. RESULTS: Of 970 patients with vaginal C. albicans isolates, 71 (7.3%) with clinically defined fluconazole-resistant C. albicans infections were identified. Relevant demographics included 45.1% African American, 43.7% aged younger than 30 years, and 43.7% with body mass index less than 25. Of the 71 patients, 58 (81.7%) received vaginal boric acid treatment. The mycological and clinical cure rates were 85.7% and 73.7%, respectively. After successful boric acid treatment and negative yeast cultures, 14.3% of patients had a mycological recurrence within 3 months. Of 31 isolates with antifungal susceptibility testing, 83.9% (26/31) were found to have minimal inhibitory concentration results consistent with fluconazole resistance. CONCLUSIONS: In a tertiary care vulvovaginal health center, fluconazole-resistant Candida albicans VVC is by no means uncommon and usually responds in the short term to treatment with boric acid. However, in the absence of maintenance boric acid, recurrence of culture-positive VVC is likely.

Vulvovaginal Candidiasis: A Review of the Evidence for the 2021 Centers for Disease Control and Prevention of Sexually Transmitted Infections Treatment Guidelines.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common cause of vulvovaginal itching and discharge. This article discusses the latest CDC STI Treatment Guidelines for VVC. METHODS: A literature search of relevant topics was performed, and a team of experts was convened to discuss (1) diagnosis/testing modalities; treatment of (2) uncomplicated VVC , (3) complicated VVC, and (4) VVC caused by non-albicans yeast; (5) alternative treatment regimens; (6) susceptibility testing of yeast; Special Populations: (7) pregnancy and (8) HIV and VVC. RESULTS: Yeast culture remains the gold standard for diagnoses. Newer molecular assays have been developed for the diagnosis of VVC and perform well. Azole antifungals remain the treatment of choice for uncomplicated VVC. Two new drugs, TOL-463 and recently FDA-approved ibrexafungerp, appeared promising in clinical trials. For recurrent VVC, oteseconazole, not yet commercially available, may represent a new option. For non-albicans yeast infections in symptomatic patients, boric acid appears useful. No evidence supports the use of alternative treatments, including probiotics. Fluconazole during pregnancy may be associated with spontaneous abortion and craniofacial and heart defects. In women with HIV infection, lower CD4+ T-cell counts are associated with increased rates of VVC, and VVC is associated with increased viral shedding. Treatment measures in women with HIV infection are identical to those women without HIV infection. CONCLUSIONS: There has been significant new knowledge generated about VVC since the 2015 CDC Guidelines which have led to changing recommendations.

Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis.

BACKGROUND: Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis. METHODS: Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10). RESULTS: Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events. CONCLUSIONS: Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis. CLINICAL TRIALS REGISTRATION: NCT03253094.

Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303).

BACKGROUND: Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC. METHODS: Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4). RESULTS: Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity. CONCLUSIONS: Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

A Randomized Phase 2 Study of VT-1161 for the Treatment of Acute Vulvovaginal Candidiasis.

BACKGROUND: Acute vulvovaginal candidiasis (VVC) is common among women, but current azole antifungal treatments are often associated with safety and resistance issues. VT-1161 (oteseconazole) is an oral agent with increased selectivity for fungal CYP51. In this phase 2 clinical study, we evaluated the efficacy and safety of VT-1161 vs fluconazole in participants with moderate to severe acute VVC. METHODS: Participants presenting with an acute episode of VVC (n = 55) were randomized to receive VT-1161 300 mg once daily (q.d.) for 3 days, 600 mg q.d. for 3 days, or 600 mg twice daily (b.i.d.) for 3 days or to receive a single dose of fluconazole 150 mg (FDA-approved dose to treat acute VVC). Participants were followed for 6 months. The primary outcome was the proportion of participants with therapeutic (clinical and mycological) cure at day 28. RESULTS: A larger proportion of participants in the per-protocol population experienced therapeutic cure in the VT-1161 300 mg q.d. (75.0%), VT-1161 600 mg q.d. (85.7%), and VT-1161 600 mg b.i.d. (78.6%) groups vs the fluconazole group (62.5%); differences were not statistically significant. At 3 and 6 months, no participants in the VT-1161 groups vs 28.5% and 46.1% in the fluconazole group, respectively, had evidence of mycological recurrence. No serious adverse events or treatment-emergent adverse events leading to discontinuation were reported. CONCLUSIONS: The majority of participants across all treatment groups achieved therapeutic cure at day 28. VT-1161 was well tolerated at all dose levels through 6 months of follow-up. CLINICAL TRIALS REGISTRATION: NCT01891331.

Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study.

BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis. METHODS: Women with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6-12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups. RESULTS: Between April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%-97.4%] vs 1.5% [95% CI: .0%-8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%-98.9%] vs 1.7% [95% CI: .0%-8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed. CONCLUSIONS: A single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV. CLINICAL TRIALS REGISTRATION: NCT03935217.

Clinical Validation of the Aptima Bacterial Vaginosis and Aptima Candida/Trichomonas Vaginitis Assays: Results from a Prospective Multicenter Clinical Study.

Infectious vaginitis due to bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis accounts for a significant proportion of all gynecologic visits in the United States. A prospective multicenter clinical study was conducted to validate the performance of two new in vitro diagnostic transcription-mediated amplification nucleic acid amplification tests (NAATs) for diagnosis of BV, VVC, and trichomoniasis. Patient- and clinician-collected vaginal-swab samples obtained from women with symptoms of vaginitis were tested with the Aptima BV and Aptima Candida/Trichomonas vaginitis (CV/TV) assays. The results were compared to Nugent (plus Amsel for intermediate Nugent) scores for BV, Candida cultures and DNA sequencing for VVC, and a composite of NAAT and culture for T. vaginalis The prevalences of infection were similar for clinician- and patient-collected samples: 49% for BV, 29% for VVC due to the Candida species group, 4% for VVC due to Candida glabrata, and 10% for T. vaginalis Sensitivity and specificity estimates for the investigational tests in clinician-collected samples were 95.0% and 89.6%, respectively, for BV; 91.7% and 94.9% for the Candida species group; 84.7% and 99.1% for C. glabrata; and 96.5% and 95.1% for T. vaginalis Sensitivities and specificities were similar in patient-collected samples. In a secondary analysis, clinicians' diagnoses, in-clinic assessments, and investigational-assay results were compared to gold standard reference methods. Overall, the investigational assays had higher sensitivity and specificity than clinicians' diagnoses and in-clinic assessments, indicating that the investigational assays were more predictive of infection than traditional diagnostic methods. These results provide clinical-efficacy evidence for two in vitro diagnostic NAATs that can detect the main causes of vaginitis.

Fractionated CO2 Laser as Therapy in Recalcitrant Lichen Sclerosus.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the fractionated CO2 laser in treating recalcitrant lichen sclerosus (LS). MATERIALS AND METHODS: The study population was 40 women diagnosed with LS who were symptomatic despite medical treatment. Patients had at least 2 or more laser sessions with a 2-month follow-up visit at the Drexel Vaginitis Center. A fractionated CO2 laser was used on affected areas at mild or standard power settings. Analyses were performed of changes in symptom rating scales, verbal reports, and physical examination findings. RESULTS: In the LS cohort of 40 patients, 22 women (55%) experienced symptoms that had persisted longer than 5 years before treatment. After the appropriate laser sessions, 72.5% of women described their improvement as significant or more than 66% improvement. In addition, there was a statistically significant reduction in vaginal pain, itching, dyspareunia, and dysuria. The presence of white epithelium decreased 20% after treatment. Furthermore, the mean corticosteroid use declined from 4.28 times per week to 2.04 times per week, indicating a resolution of many symptoms. CONCLUSIONS: The fractionated CO2 laser may be a helpful approach for managing LS that is unresponsive to traditional treatment options.

Metronidazole-Resistant Trichomoniasis: Beneficial Pharmacodynamic Relationship With High-Dose Oral Tinidazole and Vaginal Paromomycin Combination Therapy.

Metronidazole-resistant trichomoniasis is an uncommon condition that presents significant therapeutic challenges. Combination therapy with high-dose oral tinidazole and vaginal paromomycin cream has been uniformly successful. We present a case report of a patient who responded to combination therapy with high-dose oral tinidazole and intravaginal paromomycin.

Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common infection affecting women worldwide. Reports of patterns/risk factors/trends for episodic/recurrent VVC (RVVC) are largely outdated. The purpose of this study was to obtain current patient perspectives of several aspects of VVC/RVVC. METHODS: Business cards containing on-line survey information were distributed to healthy volunteers and patients seeking standard, elective, or referral gynecologic care in university-affiliated Obstetrics/Gynecology clinics. The internet-based questionnaire was completed by 284 non-pregnant women (78% Caucasian, 14% African American, 8% Asian). RESULTS: The majority of the participants (78%) indicated a history of VVC with 34% defined as having RVVC. The most common signs/symptoms experienced were itching, burning and redness with similar ranking of symptoms among VVC and RVVC patients. Among risk factors, antibiotic use ranked highest followed by intercourse, humid weather and use of feminine hygiene products. A high number of respondents noted 'no known cause' (idiopathic episodes) that was surprisingly similar among women with a history of either VVC or RVVC. VVC/RVVC episodes reported were primarily physician-diagnosed (73%) with the remainder mostly reporting self-diagnosis and treating with over-the-counter (OTC) medications. Most physician-diagnosed attacks utilized a combination of pelvic examination and laboratory tests followed by prescribed antifungals. Physician-treated cases achieved a higher level of symptom relief (84%) compared to those who self-medicated (57%). The majority of women with RVVC (71%) required continual or long-term antifungal medication as maintenance therapy to control symptoms. CONCLUSIONS: Current patient perspectives closely reflect historically documented estimates of VVC/RVVC prevalence and trends regarding symptomatology, disease management and post-treatment outcomes.

CD101 Topical Compared With Oral Fluconazole for Acute Vulvovaginal Candidiasis: A Randomized Controlled Trial.

OBJECTIVES: Vulvovaginal candidiasis (VVC) is an infection of the vagina's mucous membranes, caused by Candida albicans in more than 90% of acute VVC. Several topical and oral azole agents are available in a variety of formulations, and all seem to have similar effectiveness. Azoles are fungistatic, meaning that the fungi are inhibited from growth or replication but are not eradicated. Recurrent infection and developing azole resistance demonstrate a significant need for alternative treatments. MATERIALS AND METHODS: One hundred twenty-six women were randomized to 1 of the following 3 treatment cohorts: CD101 3% gel (n = 50) applied intravaginally on days 1 and 2, CD101 6% ointment (n = 50) applied intravaginally on day 1, or oral fluconazole 150 mg (n = 26) on day 1. Primary outcomes of clinical and mycological cure, as demonstrated by changes in the vaginal scores and mycological culture, were assessed on day 7 (±2 days), day 14 (±2 days), and day 28 (±7 days). Safety assessments included treatment-emergent adverse events. RESULTS: Ninety-nine women with positive Candida culture remained in the modified intent-to-treat population with 40 in each CD101 arm and 19 in the fluconazole arm. In the CD101 gel, CD101 ointment, and oral fluconazole groups, 35%, 30%, and 52.6% demonstrated clinical cure and 45%, 40%, and 57.9% had mycological cure at day 28, respectively. CONCLUSIONS: CD101 3% gel and CD101 6% ointment were well tolerated and produced similar rates of clinical and mycological cure in patients with an acute, moderate-to-severe episode of VVC. However, cure rates for these 2 formulations and regimens of CD101 were lower than those in patients treated with fluconazole.

A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC. Methods: This exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC. Results: The study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B- and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). The analysis of evaluable patients, which combined patients aged <40 years (77%) and ≥40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099). Conclusions: In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged <40 years. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC. Clinical Trials Registration: NCT01926028.

Diagnostic Performance of a Molecular Test versus Clinician Assessment of Vaginitis.

Vaginitis is a common complaint, diagnosed either empirically or using Amsel's criteria and wet mount microscopy. This study sought to determine characteristics of an investigational test (a molecular test for vaginitis), compared to reference, for detection of bacterial vaginosis, Candida spp., and Trichomonas vaginalis Vaginal specimens from a cross-sectional study were obtained from 1,740 women (≥18 years old), with vaginitis symptoms, during routine clinic visits (across 10 sites in the United States). Specimens were analyzed using a commercial PCR/fluorogenic probe-based investigational test that detects bacterial vaginosis, Candida spp., and Trichomonas vaginalis Clinician diagnosis and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet mount) were also employed to detect the three vaginitis causes. All testing methods were compared to the respective reference methods (Nugent Gram stain for bacterial vaginosis, detection of the Candida gene its2, and Trichomonas vaginalis culture). The investigational test, clinician diagnosis, and in-clinic testing were compared to reference methods for bacterial vaginosis, Candida spp., and Trichomonas vaginalis The investigational test resulted in significantly higher sensitivity and negative predictive value than clinician diagnosis or in-clinic testing. In addition, the investigational test showed a statistically higher overall percent agreement with each of the three reference methods than did clinician diagnosis or in-clinic testing. The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis.

A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of orally administered VT-1161 in the treatment of recurrent vulvovaginal candidiasis.

BACKGROUND: Lanosterol demethylase is an enzyme that is essential for fungal growth and catalyzes an early step in the biosynthetic pathway of ergosterol, which is a sterol that is required for fungal cell membrane formation and integrity. Lanosterol demethylase is the molecular target of the class of drugs referred to as "azole antifungals." VT-1161 is a novel, oral, selective inhibitor of fungal lanosterol demethylase and is being developed for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: We evaluated the efficacy and safety of 4 dosing regimens of oral VT-1161 compared with placebo in women with recurrent vulvovaginal candidiasis, which was defined as at least 3 symptomatic episodes of acute vulvovaginal candidiasis within a 12-month period. STUDY DESIGN: Two hundred fifteen women with a documented history of recurrent vulvovaginal candidiasis and who, at screening, were experiencing an episode of acute vulvovaginal candidiasis (acute vulvovaginal candidiasis; composite vulvovaginal signs and symptoms score of ≥3 and a positive potassium hydroxide test for yeast) were enrolled. After treatment of the acute infection with fluconazole, subjects were assigned randomly to 1 of 5 treatment regimens: (1) VT-1161 150 mg once daily for 7 days, then 150 mg once weekly for 11 weeks, followed by a once-weekly dose of placebo for 12 weeks; (2) VT-1161 300 mg once daily for 7 days, then 300 mg once weekly for 11 weeks, followed by a once-weekly dose of placebo for 12 weeks; (3) VT-1161 150 mg once daily for 7 days, then 150 mg once weekly for 23 weeks; (4) VT-1161 300 mg once daily for 7 days, then 300 mg once weekly for 23 weeks; or (5) a matching placebo regimen for 24 weeks. The primary efficacy outcome was the proportion of subjects with ≥1 culture-verified acute vulvovaginal candidiasis episodes through week 48. RESULTS: In the intent-to-treat population, the proportion of subjects with ≥1 acute vulvovaginal candidiasis episodes ranged from 0-7% across the 4 VT-1161 arms vs 52% in the placebo arm, with all arms achieving statistical significance vs placebo. VT-1161 was well-tolerated with a favorable safety profile, and the incidence of adverse events was lower in all VT-1161 arms compared with placebo. In addition, no patient in any VT-1161 arm discontinued the study early because of an adverse event or laboratory abnormality. There was also no evidence of an adverse effect of VT-1161 on liver function or electrocardiogram recordings. CONCLUSION: In this study, VT-1161 was shown to be efficacious and safe in the treatment of patients with recurrent vulvovaginal candidiasis. These data strongly support further clinical investigation of VT-1161 for the treatment of recurrent vulvovaginal candidiasis.

Long-Term Outcomes of Women With Recurrent Vulvovaginal Candidiasis After a Course of Maintenance Antifungal Therapy.

OBJECTIVES: Data about long-term clinical outcome after a course of maintenance fluconazole in those with recurrent vulvovaginal candidiasis (RVVC) is lacking. We aimed to determine the rate of recurrence at a minimum of 6 months after completion of maintenance therapy. METHODS: A retrospective analysis of women with Candida albicans RVVC from January 2008 to January 2017 was performed using chart review to obtain information about recurrence after maintenance therapy. Patients were considered resolved if they had no further episodes of candidiasis, sporadic with less than 3 episodes yearly and ongoing with greater than 3 episodes yearly. RESULTS: Approximately 1,672 patients with C. albicans vaginal isolates were identified. Of these, 201 met the criteria for RVVC. The mean age was 40.4 years; 151 (77.4%) were white, 133 (66.2%) had comorbid vulvar conditions, and 76 (37.8%) had a risk factor for vulvovaginal candidiasis. One hundred twenty complete charts were further analyzed. The mean length of follow-up after discontinuing maintenance therapy was 39.9 months. After the initial course, 23 (19.2%), 21 (17.5%), and 76 (63.3%) were resolved, sporadic and ongoing, respectively. Risk factors, comorbid vulvar conditions, obesity, menopause status, and length of therapy were not associated with relapse. Age 40 or older was associated with relapse (p = .018). Of the 201 total patients with RVVC, 22 (10.9%) of patients self-reported at least 1 adverse event. The most common was gastrointestinal symptoms (8 [4%]). CONCLUSIONS: Although RVVC can be controlled, relapse is common after an initial course of maintenance fluconazole. Ongoing maintenance remains the most effective treatment option.

A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis.

BACKGROUND: A novel single oral dose granule formulation of secnidazole 2 g, a 5-nitroimidazole with a longer half-life (∼17 hours) than metronidazole (∼8 hours), is being developed to treat bacterial vaginosis. OBJECTIVE: We sought to evaluate the effectiveness and safety of single-dose secnidazole 2 g compared to placebo for the treatment of women with bacterial vaginosis. STUDY DESIGN: In all, 189 women with bacterial vaginosis were randomized 2:1 to receive a single oral dose of secnidazole 2 g (N = 125) or matched placebo (N = 64) at 21 centers in the United States. The primary endpoint was the proportion of clinical outcome responders, defined as those with: (1) normal vaginal discharge; (2) negative 10% potassium hydroxide whiff test; and (3) <20% clue cells of total epithelial cell count on microscopic examination of the vaginal wet mount, using saline at the test of cure/end of study visit (study days 21-30). Secondary efficacy analyses included clinical cure rates, defined as: (1) responders with normal vaginal discharge; (2) negative potassium hydroxide whiff tests; and (3) clue cells <20% assessed at the interim visit (study days 7-14), and test of cure/end of study (study days 21-30). In addition, based on the 2016 US Food and Drug Administration draft guidance, patients with baseline Nugent scores 7-10 were evaluated for clinical cure using the following clinical assessments on study days 7-14: (1) resolution of the abnormal vaginal discharge; (2) a negative potassium hydroxide whiff test; and (3) clue cells <20%. The study was designed and powered to demonstrate the efficacy of single-dose secnidazole 2 g compared to placebo; safety and tolerability were also assessed. Due to a prespecified institutional review board-approved protocol calling for withdrawal of randomized, treated patients with a Nugent score <4 or with a separate sexually transmitted infection, this modified intent-to-treat population was the primary analysis population. Statistical comparisons used a stratified Cochran-Mantel-Haenszel test with a .05 level of significance (2-sided). RESULTS: Single-dose secnidazole 2 g was superior to placebo for the primary and all secondary efficacy measures in the modified intent-to-treat population, with clinical outcome responder rates of 53.3% (57/107) vs 19.3% (11/57; P < .001). Clinical cure rates, based on an alternate definition of responder, which accounted for resolution of abnormal discharge consistent with bacterial vaginosis, were consistent with the clinical outcome responder rate analysis (58.9% vs 24.6%; P < .001) for single-dose secnidazole 2 g vs placebo. Clinical cure rates based on the 2016 US Food and Drug Administration guidance were 64.0% vs 26.4% for single-dose secnidazole 2 g vs placebo. Based on the investigator's clinical assessment at the test of cure/end of study visit, significantly more patients receiving single-dose secnidazole 2 g vs placebo required no additional bacterial vaginosis treatment (68.0% [68/100] vs 29.6% [16/54]; P < .001). Adverse events considered by the investigator to be related to study drug occurred in only 20.0% of single-dose secnidazole 2 g-treated patients vs 10.9% of placebo patients, and they included diarrhea (4.0% vs 1.6%), headache (4.0% vs 3.1%), nausea (4.8% vs 1.6%), and vulvovaginal candidiasis (4.0% vs 3.1%). CONCLUSION: Single-dose secnidazole 2 g was superior to placebo on all primary and secondary outcomes and was well tolerated; these results support its role for the treatment of women with bacterial vaginosis.

Chronic Cervicitis: Presenting Features and Response to Therapy.

OBJECTIVES: Chronic nongonococcal nonchlamydial cervicitis is a condition of unknown etiology. Data about treatment options are limited. Our goal was to review a single center's experience in managing women with chronic NGNCC. METHODS: We evaluated all encounters at a tertiary care center with ICD-9 code for cervicitis between April 2008 and March 2014. Cases were defined by having two of the following 3 diagnostic criteria: mucopurulent discharge noted by (1) patient or (2) practitioner, and (3) cervical bleeding upon gentle probing. All women had negative nucleic acid amplification testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Information regarding patient demographics, symptoms, findings, treatment, and outcomes were analyzed. Cure was defined as resolution of patient-specific diagnostic criteria. RESULTS: Sixty-one women were identified. The mean age was 31 years; 73.7% were white, and 59% were nulliparous. The mean duration of symptoms was 25.2 months. Initially, all 61 patients received one of 3 antibiotic treatments. The cure rate after initial antibiotic treatment was 65.6%. Nineteen patients required at least one further treatment. Additional treatments included secondary antibiotics, hormonal treatments, vaginal hydrocortisone, silver nitrate, cryotherapy, and loop excision electrosurgical procedure. Cure rates were as follows: 57.9% with antibiotics, 50% with hormone treatment, 0% with hydrocortisone, 100% with silver nitrate, 0% with cryotherapy, and 100% with loop electrosurgical excisional procedure. Of the initial 61 women, 93.4% were eventually cured. CONCLUSIONS: Nongonococcal nonchlamydial cervicitis is a condition that can cause unremitting symptoms. Most patients will respond to antibiotics, although other treatments including surgery may be necessary.

Non-albicans Candida Vulvovaginitis: Treatment Experience at a Tertiary Care Vaginitis Center.

OBJECTIVES: The aims of this study are to analyze a cohort of women with vulvovaginal symptoms and positive cultures for non-albicans Candida (NAC) to determine whether yeast was responsible for their symptoms and to evaluate the mycological effectiveness of various regimens. METHODS: This observational study was performed from retrospective chart review of patients with positive NAC cultures between April 1, 2008, and January 31, 2011, at a tertiary care vaginitis center. Patient intake demographics were entered into a database. Follow-up visits were analyzed for data about patient treatments and outcomes. Patients were considered a clinical cure if their symptoms were significantly improved and mycologic cure (MC) if later yeast cultures were negative. If clinical symptoms improved at the same time as MC, the isolate was considered the proximate cause for the symptoms. RESULTS: One hundred eight patients meeting entry criteria were analyzed. Boric acid was effective at obtaining MC in 32 (78%) of 41 patients with C. glabrata, 3 of 3 patients with C. tropicalis, and 3 of 3 patients with C. lusitaniae. Fluconazole was effective as initial treatment for 3 (60%) of 5 patients with C. glabrata and 13 (81%) of 16 patients with C. parapsilosis. In 52.7% of C. glabrata, 66.7% of C. parapsilosis, and 57.1% of C. tropicalis cases, effective antifungal therapy led to symptom improvement. CONCLUSIONS: In a tertiary care vaginitis center, NAC, when isolated on culture, caused clinically significant infections in approximately half of symptomatic patients. A majority of infections can be effectively treated with boric acid or fluconazole regardless of the non-albicans Candida species.

A Review of Evidence-Based Care of Symptomatic Trichomoniasis and Asymptomatic Trichomonas vaginalis Infections.

Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of this infection, which affects 11% of women aged ≥40 years and a disproportionately high percentage of black women. Particularly high prevalences have been identified among sexually transmitted disease (STD) clinic patients and incarcerated individuals. This article reviews and updates scientific evidence in key topic areas used for the development of the 2015 STD Treatment Guidelines published by the Centers for Disease Control and Prevention. Current evidence is presented regarding conditions associated with Trichomonas vaginalis infection, including human immunodeficiency virus (HIV) and pregnancy complications such as preterm birth. Nucleic acid amplification tests and point-of-care tests are newly available diagnostic methods that can be conducted on a variety of specimens, potentially allowing highly sensitive testing and screening of both women and men at risk for infection. Usually, trichomoniasis can be cured with single-dose therapy of an appropriate nitroimidazole antibiotic, but women who are also infected with HIV should receive therapy for 7 days. Antimicrobial resistance is an emerging concern.

Trichomonas vaginalis Infection in a Tertiary Care Vaginitis Center.

BACKGROUND: Trichomonas vaginalis infection (TVI) is one of the most common sexually transmitted diseases in the United States. We sought to determine the features of TVI in a referral-based vaginitis center, focusing on diagnosis and treatment of difficult cases. METHODS: We conducted a retrospective review of all patients with TVI, based on International Classification of Diseases, Ninth Revision codes, seen at the Drexel Vaginitis Center between January 2008 and November 2013. Information collected on each subject included demographics, symptoms, examination findings, diagnostic tests, and treatment regimens. RESULTS: Of approximately 4000 new patient visits during our study period, 80 subjects were identified with TVI. Twenty subjects presented with known TVI, with most having clinically resistant infections. Diagnosis was confirmed by saline microscopy in 45%, OSOM rapid test in 40%, and clinical history in the remaining 15%. Treatment regimens varied: 20% received single 2-g dosing of either metronidazole or tinidazole, 50% received high-dose regimens, 20% received therapy with vaginal paromomycin, and 10% underwent desensitization for nitroimidazole allergy. Sixty subjects had newly diagnosed TVI, with 35% diagnosed by saline microscopy, 41.7% by OSOM rapid test, and 23.3% by APTIMA. Treatment regimens for these subjects included single 2-g dosing in 88.3%, high-dose regimen in 8.3%, and other formulations in the remaining 3.4%. In total, 80% of our subjects returned for follow-up; all of whom were cured. CONCLUSIONS: T. vaginalis infection is a rare condition in a tertiary care vaginitis center and often requires nonstandard treatments. Among those who returned for follow-up, the cure rate was 100%.