Efficacy and safety of oral ibrexafungerp for the treatment of acute vulvovaginal candidiasis: a global phase 3, randomised, placebo-controlled superiority study (VANISH 306).

OBJECTIVE: To evaluate the efficacy and safety of ibrexafungerp versus placebo for acute vulvovaginal candidiasis (VVC) treatment. DESIGN: Global phase 3, randomised, placebo-controlled superiority study. SETTING: Study sites in the USA (n = 19) and Bulgaria (n = 18). POPULATION: Female patients aged ≥12 years with acute VVC and a vulvovaginal signs and symptoms (VSS) score ≥4 at baseline. METHODS: Patients were randomly assigned 2:1 to ibrexafungerp (300 mg twice for 1 day) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was the percentage of patients with a clinical cure (VSS = 0) at the test-of-cure visit (day 11 ± 3). Secondary endpoints included percentages of patients with mycological eradication, clinical cure and mycological eradication (overall success), clinical improvement (VSS ≤1) at test-of-cure visit, and complete resolution of symptoms at follow-up visit (day 25 ± 4). RESULTS: At the test-of-cure visit, patients receiving ibrexafungerp had significantly higher rates of clinical cure (63.3% [119/188] versus 44.0% [37/84]; P = 0.007), mycological eradication (58.5% [110/188] versus 29.8% [25/84]; P < 0.001), overall success (46.1% [82/188] versus 28.4% [23/84]; P = 0.022) and clinical improvement (72.3% [136/188] versus 54.8% [46/84]; P = 0.01) versus those receiving placebo. Symptom resolution was sustained and further increased with ibrexafungerp (73.9%) versus placebo (52.4%) at follow-up (P = 0.001). Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mild to moderate in severity. CONCLUSIONS: Ibrexafungerp demonstrated statistical superiority over placebo for the primary and secondary endpoints. Ibrexafungerp is a promising novel, well-tolerated and effective oral 1-day treatment for acute VVC. TWEETABLE ABSTRACT: Ibrexafungerp is statistically superior to placebo for the treatment of vulvovaginal candidiasis.

Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications.

Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.6%) were resistant (MICs, >or=64 microg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 micro g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were 1 microg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 microg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.

Gluteal necrotizing myofascitis: an unusual delayed complication of abdominal sacrocolpopexy.

Persistent low back pain developed in a 51-year-old woman after she had undergone abdominal sacrocolpopexy. Four months postoperatively, necrotizing myofascitis developed in her gluteal muscles. The infected mesh, which had eroded into the vagina, was removed. Cultures of the infected mesh and abscesses grew common vaginal flora, including Gardnerella vaginalis and Actinomyces.

Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis.

Treatment of patients with metronidazole-refractory vaginal trichomoniasis constitutes a major therapeutic challenge, and treatment options are extremely limited. Although the majority of patients infected with trichomonads, who demonstrate reduced in vitro susceptibility to metronidazole, respond to high-dose but poorly tolerated regimens of metronidazole, clinical failure is by no means uncommon. We report a cure rate of 22 (92%) of 24 patients with refractory trichomoniasis treated with high doses of oral and vaginal tinidazole. This series included 15 cases with increased in vitro minimal lethal concentration values of metronidazole. Tinidazole, despite the high doses used, was extremely well tolerated, with few side effects. Topical paromomycin was effective in 7 (58%) of 12 patients treated, but frequent local vulvovaginal adverse reactions precluded extensive use. Widespread reports of metronidazole resistance and limited treatment options emphasize the need for additional trichomonacidal agents.

Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole.

OBJECTIVE: An attempt was made to validate recent recommendations that women with complicated Candida vaginitis (severe or recurrent, non-albicans Candida spp or abnormal host) require longer-duration antifungal therapy to achieve clinical cure and mycologic eradication. STUDY DESIGN: A prospective, multicenter, randomized, double-blind study was performed comparing a single dose of 150 mg of fluconazole with 2 sequential 150-mg doses of fluconazole given 3 days apart. RESULTS: Five hundred fifty-six women with severe or recurrent Candida vaginitis were enrolled, and 398 had at least one postbaseline evaluation (intent to treat) and of these 309 were fully evaluable (efficacy-valid). At baseline, 92% of vaginal isolates were Candida albicans. The 2-dose fluconazole regimen achieved significantly higher clinical cure rates in women with severe vaginitis when evaluated on day 14 (P =.015) and higher clinical and mycologic responses persisted at day 35. Women with recurrent but not severe vaginitis did not benefit clinically short term by the additional fluconazole dose. Multivariate logistic regression analysis showed that being infected with non-albicans Candida predicted significantly reduced clinical and mycologic response regardless of duration of therapy. Fluconazole therapy was well tolerated and free of serious adverse effects. CONCLUSION: Treatment of Candida vaginitis requires individualization, and women with severe Candida vaginitis achieve superior clinical and mycologic eradication with a 2-dose fluconazole regimen.

Chronic vulvovaginal candidiasis.

Frequently ignored by the medical community, chronic vulvovaginal symptoms are relatively common and can frustrating for patients and physicians. Establishing a proper diagnosis will lay the foundation for an effective therapeutic therapeutic plan. Fungal cultures are an important component of the work-up. The most common causes of chronic vaginal symptoms are recurrent vulvovaginal candidiasis (RVVC), vulvar vestibulitis syndrome and irritant dermatitis. In patients with RVVC caused by Candida albicans, host factors may play an important role. Long-term oral antifungal therapy will break the pattern of recurrence in many patients. Infections caused by other species of yeast may be more resistant to standard treatment approaches.

Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study.

OBJECTIVE: Patients with chronic idiopathic vulvar vestibulitis have increased mast cells when biopsied, and cromolyn has been suggested as a treatment. The purpose of this study was to assess the efficacy of 4% cromolyn cream in women with vulvar vestibulitis. METHODS: A prospective, double blind, randomised, placebo controlled study was initiated at two centres. Patients with vulvar vestibulitis were assigned to apply cromolyn or placebo cream to the vestibule. Symptoms (burning, irritation) and signs (erythema, extent of erythema, tenderness) were recorded on a 0-3 scale. In the sexually active patient subgroup, dyspareunia was also evaluated. RESULTS: 13 of the 26 evaluable patients received cromolyn. Patients in the cromolyn arm were more likely to have failed therapy with amitriptyline (p = 0.05), but the two groups were otherwise similar upon study entry. Overall, scores decreased from a median of 9 to 5 (p = 0.001) during the study, but the level of improvement was similar between both groups. Improvement was unrelated to duration of symptoms, fluconazole use, or sexual activity. Five patients (38%) taking cromolyn and six (46%) taking placebo felt they had a 50% or greater reduction in symptoms. In the 21 sexually active patients, the total score decreased from a mean of 12 to 8 (p = 0.005), but there was no statistically significant difference between study arms. CONCLUSIONS: Cromolyn cream did not confer a significant benefit in patients with vulvar vestibulitis. The large placebo response suggests the need for large well controlled studies of other treatment modalities.

Vulvar Vestibulitis Syndrome: A Post-infectious Entity?

Vulvar vestibulitis syndrome, a condition characterized by inflammation of the vaginal introitus, causes chronic vulvar pain, particularly with intercourse. It occurs in at least 15% of women with chronic vulvovaginal symptoms, and it is a common cause of sexual dysfunction and resulting comorbidities. Because 80% of women with vulvar vestibulitis syndrome describe an acute onset of symptoms, an infectious etiology has been suspected but never proven. Initially, human papillomavirus infection was thought to be the cause, but recent controlled studies dispute this earlier supposition. Vulvovaginal candidiasis may play an important role in the development of this condition.

Urinary tract infections in women with bacterial vaginosis.

OBJECTIVE: To evaluate the risk of urinary tract infections in women with bacterial vaginosis. METHODS: One hundred twenty-nine women who presented for routine gynecologic examinations were evaluated for bacterial vaginosis and urinary tract infections between June 1998 and March 1999. RESULTS: Sixty-seven women had bacterial vaginosis and 62 women did not. Fifteen women with bacterial vaginosis (22.4%) had urinary tract infections, compared with six (9.7%) of those without it. Bacterial vaginosis was associated with an increased risk of urinary tract infections (odds ratio 2.79; 95% confidence interval 1.05, 8.33). CONCLUSION: Women with bacterial vaginosis are at increased risk for urinary tract infections.

Terconazole cream for non-Candida albicans fungal vaginitis: results of a retrospective analysis.

OBJECTIVE: Although it is FDA-approved for use in vulvovaginal candidiasis caused by non-Candida albicans species, terconazole cream has not been been studied in patients with these infections. We sought to assess the clinical and mycological efficacy of terconazole cream in women with non-C. albicans vaginitis. METHODS: The records of patients who had received a 7-day course of terconazole cream for culture-proved non-C. albicans vaginitis were reviewed. Data with regard to patient demographics, clinical and mycologic response to therapy within 1 month of treatment, and outcome with other antifungal therapies were analyzed. RESULTS: Twenty-eight patients received terconazole cream for non-C. albicans infections. Three patients did not return for follow-up. The median age was 45 years. Seven (28%) patients were nulliparous. The median duration of symptoms was 3 years. Nine patients (36%) had received terconazole within the 6 months prior to referral. Overall, there were 20 C. glabrata cases, 3 C. parapsilosis, and 2 C. lusitaniae. Fourteen (56%) patients achieved a mycologic cure; 11 (44%) noted a resolution of their symptoms. Prior terconazole use was not associated with treatment failure (P = 0.09). Ten failures received boric acid suppositories as subsequent treatment; a cure was effected in 4 (40%). Two of three patients (67%) were eventually cured with flucytosine cream. Five (20 %) patients remained uncured. CONCLUSIONS: Terconazole cream may be an appropriate first-line treatment for non C. albicans vaginitis, even in patients who have previously received the drug.

Intravesical foreign body and vesicovaginal fistula: a rare complication of a neglected pessary.

A silicone Gellhorn pessary, 3 inches in diameter, neglected for several years in an elderly woman, eroded through the anterior vaginal wall, ultimately to lie entirely within the bladder. General anesthesia and bilateral deep full-length Schuchardt's incisions were required to remove it. A Latzko procedure was done at a later date to close the large vesicovaginal fistula; similar Schuhardt's incisions were again used.

Creation of neovagina by laparoscopic Vecchietti operation.

The Vecchietti operation is a surgical technique that creates a neovagina by dilation in 7-9 days. The authors report a case of a 17-year-old woman with müllerian agenesis, Mayer-Rokitansky-Kuster-Hauser syndrome, in whom the Vecchietti operation was performed. A neovagina with a depth of 11 cm was created in 7 days. There were no complications, and the functional result was excellent.

Vaginitis in the adolescent patient.

For any clinician involved in the health care of women, vaginitis remains an unavoidable problem. Vaginitis accounts for an estimated 10 million office visits each year, and it remains the most common reason for patient visits to obstetrician-gynecologists. Despite extensive self-diagnosis and self-treatment for vaginal symptoms in all age groups, important questions persist about the accuracy of such an approach. This article addresses these questions and approaches.

Managing Resistant Trichomonas Vaginitis.

Vaginal trichomoniasis is a sexually transmitted disease of worldwide importance that is commonly treated with metronidazole. Although surprisingly uncommon, resistance to metronidazole has nevertheless been widely reported. Patients with suspected resistant trichomoniasis should have the diagnosis confirmed either by visualization of motile trichomonads on saline microscopy or by culture. In addition, reinfection from a partner must be ruled out through a careful history. Data regarding treatment of metronidazole-resistant trichomoniasis are mainly limited to case reports or series. Most cases can be treated successfully with increasing doses of oral metronidazole. Other promising options include oral tinidazole and topical paromomycin cream.

Difficult-to-treat trichomoniasis: results with paromomycin cream.

Vaginal trichomoniasis poses a difficult therapeutic challenge when metronidazole is ineffective or contraindicated. We conducted a retrospective study of 6.25% paromomycin cream in the treatment of nine women referred with cases of vaginal trichomoniasis where metronidazole resistance or allergy was present. Results obtained immediately and 1 month after treatment were reviewed. The median age of the patients was 46 years; four women were nulliparous. The median symptom duration was 1 year. Five women were allergic to metronidazole. In four cases, resistance to high doses of metronidazole was demonstrated. Smears or cultures were positive immediately after treatment for three patients; a fourth relapsed 2 weeks later. Of these patients for whom treatment failed, one was cured with a 3-week course of paromomycin cream, and another was successfully treated with paromomycin cream and oral tinidazole. Three patients developed vaginal ulcerations that resolved spontaneously. Adverse effects may be a result of local formulation. Paromomycin cream was useful for treatment of cases of trichomonas infection where metronidazole resistance or allergy was encountered.

Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations.

Although it is the second most common vaginal infection in North America, vulvovaginal candidiasis is a non-notifiable disease and has been excluded from the ranks of sexually transmitted diseases. Not surprisingly, vulvovaginal candidiasis has received scant attention by public health authorities, funding agencies, and researchers. Epidemiologic data on risk factors and pathogenic mechanisms remain inadequately studied. Most important, standards of care, including diagnosis and therapy, remain undefined. A conference was held in April 1996 to define and summarize what is known and supported by scientific data in the areas of epidemiology, diagnosis, and treatment of vulvovaginal candidiasis; but, more important, the conference aimed at defining what is not known, poorly studied, and controversial. Guidelines for the treatment and diagnosis of the different forms of vulvovaginal candidiasis are suggested.

Over-the-counter and alternative medicines in the treatment of chronic vaginal symptoms.

OBJECTIVE: To investigate the use of over-the-counter and alternative medicines in women with chronic vaginal symptoms. METHODS: One hundred five patients, referred by their gynecologists for evaluation of chronic vaginal symptoms, were interviewed about their use of over-the-counter and alternative medicines during the preceding year, the amount of money spent on each, and whether or not their physicians had been informed of these treatments. RESULTS: The mean age was 36 years, and one-half had finished college. The median symptom duration was 2 years. Seventy-seven (73.3%) patients had self-treated with over-the-counter medications such as miconazole (74% of over-the-counter users), clotrimazole (38.2%), or povidone-iodine (13.2%). The median expenditure for over-the-counter use was %0 (range $2-1000). Forty-four (41.9%) had used alternative medicines, most frequently acidophilus pills orally (50%) vaginally (11.4%), yogurt orally (20.5%) or vaginally (18.2%), vinegar douches (13.6%), and boric acid (13.6%). The median expenditure for alternative medicines was $35 (range $0-1200). Fewer physicians were aware of the use of alternative (70.5%) that of over-the-counter medicines (88.3%). Although most patients thought that vulvovaginal candidiasis was the cause of their symptoms, the most common diagnoses at initial presentation were candidiasis in 29 (27.6%), vulvar vestibulitis in 18 (17.1%), irritant dermatitis in 16 (15.2%), and bacterial vaginosis in 11 (10.5%). Women who actually had candidiasis were more likely to have used alternative medicines (odds ration 2.31, 95% confidence interval 1.00, 5.42) than other patients. CONCLUSION: Women with chronic vaginal symptoms often use over-the-counter and alternative medicines that add to health care costs and are unlikely to be of benefit.

Trospectomycin in acute pelvic inflammatory disease: a preliminary report.

OBJECTIVE: The purpose of this study was to compare the clinical efficacy and safety of intravenous trospectomycin to that of cefoxitin plus doxycycline in the treatment of women hospitalized with acute pelvic inflammatory disease (PID). METHODS: Thirty-nine patients admitted with a clinical diagnosis of an acute PID were enrolled in this prospective, single-blind study. Patients were treated with either intravenous trospectomycin, 500 mg every 8 h, or intravenous cefoxitin, 2 g every 6 h, plus oral or intravenous doxycycline, 100 mg every 12 h, in a 2:1 ratio. The patients were followed for clinical response and side effects. Both groups of patients were discharged on oral doxycycline for 10 days. Appropriate cultures were obtained before starting inpatient treatment, on completion of inpatient treatment, and at 2 follow-up visits. RESULTS: The overall success rate for trospectomycin was 95.6% and for cefoxitin/doxycycline was 91.6%. This difference was not statistically significant (P = 0.63). Trospectomycin was found to be effective against Chlamydia trachomatis. CONCLUSIONS: Single-agent therapy with trospectomycin may be as effective as cefoxitin plus doxycycline in the treatment of women hospitalized with acute PID.

Significance of genital mycoplasmas in pelvic inflammatory disease: innocent bystander!

OBJECTIVE: Our objective was to determine the role of Mycoplasma hominis and Ureaplasma urealyticum in pelvic inflammatory disease (PID). METHODS: The clinical and microbiologic variables in 114 patients with a clinical diagnosis of PID were compared prospectively according to the isolation of M. hominis and U. urealyticum from their endometrial cavities. RESULTS: The groups were epidemiologically well matched. Clinical parameters such as temperature, leukocyte count, erythrocyte count, and C-reactive protein on admission and length of hospital stay were similar in the patients, regardless of their mycoplasma status. A significant percentage of the patients either continued or started to harbor genital mycoplasmas after the resolution of PID without any significant clinical sequelae. CONCLUSIONS: The presence of genital mycoplasmas does not change the clinical presentation and course of PID. Both M. hominis and U. urealyticum can persist or colonize the endometrium after complete recovery from PID. Therefore, the genital mycoplasmas do not seem to have a dominant pathogenic role in PID.