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.

Specific association of repetitive DNA sequences with major histocompatibility genes.

The DNA sequence organization of a 17.8-kilobase segment of porcine DNA, containing a functional major histocompatibility (MHC) gene, has been studied. The DNA flanking the MHC gene contains at least 10 distinct repetitive DNA sequence elements, each of which occurs only once within the 17.8-kilobase DNA segment. Their reiteration frequencies in the genome range from 10(2) to 10(4). The genomic organization of seven of these sequence elements has been examined; all are interspersed with other, unrelated DNA sequences. These seven repeated sequences are not generally associated in the genome. However, they appear to be nonrandomly linked in MHC-associated regions of the genome: at least two additional DNA segments containing MHC-homologous DNA also contain sequences homologous to DNA fragments bearing the seven different repeats. Of the seven sequences, four can be detected in splenic total RNA. These results suggest that these repeated elements are specifically associated with the MHC locus.

The interrelationship between ethnicity and gestational diabetes in fetal macrosomia.

OBJECTIVE: To determine the possibility of an ethnic influence on the development of macrosomia (birth weight > 90th percentile for gestational age) in gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We prospectively followed all African-American and Latino women enrolled in the Temple diabetes-in-pregnancy program. GDM was diagnosed in 103 African-American and 36 Latino women during the study period (1991-1994) according to the criteria of Carpenter and Coustan. All women were treated according to our previously published protocols. Data were collected on gestational weight gain, previous history of macrosomia, body mass index (BMI), and level of maternal glycemic control. RESULTS: Insulin therapy was required in 53 women (37.5%) to maintain fasting blood glucose levels at < 95 mg/dl and 2-h postprandial levels at < 120 mg/dl. Macrosomia developed in 50% of the neonates of Latino women versus 19% of neonates of African-American women (relative risk 2.68; 95% confidence interval 1.57-4.59). Potential confounding factors were not significantly different between the Latino and African-American women: mean blood glucose 96.6 +/- 15.7 vs. 96.5 +/- 22.4 mg/dl; BMI 29.0 +/- 5.5 vs. 31.5 +/- 8.2 kg/m2; pregnancy weight gain 29.2 +/- 12.7 vs. 30.9 +/- 20.5 lb; and parity 1.8 +/- 1.5 vs. 1.6 +/- 1.4, respectively. CONCLUSIONS: We have demonstrated that Latino women with GDM are at higher risk for having macrosomic infants in comparison with African-American women. This ethnic variation in fetal growth may be due to varying influences of in utero growth promoters among these populations as well as underlying genetic factors.

Malassezia furfur folliculitis of the vulva: olive oil solves the mystery.

BACKGROUND: In treating women with chronic fungal infections, it is important to know which organism is responsible for the infection. In the past, organisms thought to cause vaginitis and vulvitis could all be cultured on modified Sabouraud agar. CASE: We describe a case of a woman whose chronic fungal vulvar folliculitis masqueraded as squamous epithelial hyperplasia. The 46-year-old woman, taking immunosuppressive therapy for rheumatoid arthritis, was referred with an 8-month history of vulvar vesicles, itching, and burning. Her examination revealed a vulvar folliculitis. When fungal cultures were initially negative, a vulvar biopsy revealed a squamous epithelial hyperplasia. However, a fungal culture covered with sterile olive oil eventually grew Malassezia furfur, a yeast with peculiar growth requirements. She was cured with a 2-week course of fluconazole. CONCLUSION: Malassezia furfur, an organism rarely described in the vaginitis literature, can cause vulvar folliculitis in a patient on immunosuppressive therapy.

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.

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.

Saccharomyces cerevisiae vaginitis: transmission from yeast used in baking.

OBJECTIVE: To determine whether vaginitis due to Saccharomyces cerevisiae can be caused by exposure to exogenous sources of baker's yeast. METHODS: Eight women with S cerevisiae vaginitis were identified from a cohort of women referred for the evaluation of chronic vaginal symptoms. In those with high-level exposure to exogenous sources of S cerevisiae, isolates from the vagina and those sources were sent in a blinded fashion for contour-clamped homogeneous electric-field electrophoresis. RESULTS: Four women from a cohort of approximately 750 referred patients had high-level exposures to S cerevisiae. In one of these patients, electrophoresis analysis revealed similarities between the strains isolated from her vagina, her husband's fingers, and the yeast he used in his pizza shop. CONCLUSION: Saccharomyces cerevisiae vaginitis can be the result of the inoculation of this yeast from exogenous sources.

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.

Vaginal birth after cesarean section in rural Zaire. Changing concepts.

The safety of trials of labor after cesarean section has yet to be established in developing countries. Centre Médical Evangélique is a referral hospital in rural northeastern Zaire. From August 1, 1989, to January 15, 1990, 33 women with previous cesarean deliveries were offered a trial of labor. Of them, 22 (67%) had successful vaginal deliveries. The indications for the previous cesarean section did not influence the outcome of the trial of labor. There was a high rate of immediate maternal morbidity but no significant long-term morbidity. The rate of uterine dehiscence was 9.1%. The perinatal death rate, 60.1/1,000, was similar to the overall rate for the institution. Trials of labor after cesarean section are a valid therapeutic option in developing countries.

Streptococcal toxic shock-like syndrome as an unusual complication of laparoscopic tubal ligation. A case report.

Toxic shock-like syndrome due to Streptococcus pyogenes is an unusual occurrence. Previously reported cases have been the result of focal infections with S pyogenes. We present a case in which manipulation of a colonized mucosal surface during laparoscopic tubal ligation was the presumed cause of the sepsis syndrome. Whereas other reports of this syndrome have all noted concurrent infections with S pyogenes, in this instance it was unclear if toxin-mediated disease was initiated by mild endometritis or iatrogenic manipulation of a colonized mucosal surface.

PIP: In Pennsylvania, a 29-year-old woman was admitted to Temple University Health Sciences Center in Philadelphia with hypotension (100/80 mmHg), fever (105.3 degrees Fahrenheit), and a diffuse, nondesquamating erythroderma. Five weeks earlier, she had delivered her last child vaginally. Three days before admission, she had undergone endotracheal intubation so surgeons could perform a laparoscopic tubal ligation with Falope Rings. Two days before the tubal ligation, she had had a sore throat. She experienced no surgical complications and was discharged the same day as the operation. The day before her latest admission, she experienced nausea, vomiting, diarrhea, fever, chills, and diffuse abdominal pain. Upon admission, her surgical incisions were clean and dry and had no erythema. Her pulse rate was 140 beats/minute. Her respiration rate was 20/minute. The white blood cell count was 15,200 cells/cu. m (71% neutrophils, 23% band forms, 2% lymphocytes, and 4% monocytes). Her potassium level was 3.2 mmol/l. The anion gap was 22. All blood and urine cultures were negative. She experienced mild uterine tenderness. Upon admission, physicians administered ticarcillin-clavulanate and vancomycin for suspected postoperative pelvic infection. After learning that cervical and pharyngeal cultures were positive for Streptococcus pyogenes, physicians changed to ampicillin, 1 g intravenously every 6 hours. On the 6th day, she was discharged and prescribed 500 mg oral amoxicillin every 8 hours for 2 weeks. Within 2 weeks, she felt fine, had a normal physical examination, no fever, and no rash. The major signs and symptoms indicated a toxin-mediated illness. Both mucosal surfaces colonized by S. pyogenes were manipulated during laparoscopy and manipulation may have caused minor tissue injury and hyperemia with subsequent dissemination of streptococcal toxin. In conclusion, the patient had a S. pyogenes toxin-induced toxic shock-like syndrome that mimicked a pelvic wound infection with gram-negative septicemia.

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.

Neonatal care in northeast Zaire.

Neonatal care in rural northeast Zaire presents many challenges to nursing. The high infant mortality is a result of rampant infectious diseases, limited resources, and poor public education. Midwives use innovative nursing interventions to meet the basic needs of the neonate: warmth, respiration, nutrition, and prevention of infection. Interesting cultural beliefs also influence neonatal care in this area of Africa.

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.

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.

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.

Medical management of vulvar vestibulitis: results of a sequential treatment plan.

OBJECTIVE: The objectives of this study were to assess the efficacy of medical management for vulvar vestibulitis and to examine several historical variables and determine their predictive values as to which treatments will be most successful. METHODS: Seventy-four patients diagnosed with vulvar vestibulitis were evaluated. Each patient was treated using a sequence of consecutive medical therapies for vulvar vestibulitis. These therapies were topical aqueous 4% lidocaine with intercourse, topical corticosteroid therapy, oral amitriptyline, topical low-dose 5-fluorouracil (5-FU) cream, intralesional alpha-interferon, and a low-oxalate diet in combination with oral calcium citrate. The patients were followed over 3-30 months and their responses to therapy were assessed. In addition, a statistical analysis was performed to determine the positive predictive values of certain historical variables and specific treatment successes. RESULTS: Forty-nine patients reported positive responses to one of the initiated therapies. More specifically, 18.1% of the patients who used lidocaine, 33.8% who used topical corticosteroids, 57.1% who used amitriptyline, 16.7% who used 5-FU, none who received interferon, and 50% who tried a low-oxalate diet had positive responses to therapy. No historical variables were predictive of which therapies would have the most successful outcome. CONCLUSIONS: Medical management is effective in alleviating the symptoms of vulvar vestibulitis. Various aspects of a patient's history are not helpful in selecting the therapy that will be most effective.

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.

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.

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.

Perihepatic adhesions: another look.

OBJECTIVE: The objective of our study was to determine if pelvic inflammatory disease (PID) was the only cause of perihepatic adhesions. METHODS: One hundred consecutive patients undergoing elective sterilization by laparoscopy were enrolled in this study. The preoperative workup included a history, physical examination, cervical culture for Neisseria gonorrhoeae and Chlamydia trachomatis, leukocyte count, C-reactive protein, and liver-function tests. During the laparoscopic procedure, the pelvis and liver surface were inspected for evidence of any adhesions. If perihepatic adhesions were discovered in a patient without any evidence of prior PID, then cultures from the adhesion, peritoneal fluid, and tubal specimens were obtained for N. gonorrhoeae, C. trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, anaerobes, and facultative aerobes. Tubal specimens were also obtained for histologic examination. RESULTS: Of 100 patients, 7 patients had perihepatic adhesions without any laparoscopic evidence of prior PID. The preoperative cultures were negative. Three of these patients had no history of sexually transmitted disease or PID. Their anti-chlamydial antibody titers were also negative. Of the remaining 4 patients with perihepatic adhesions, 2 had a history of gonococcal or chlamydial infection and 2 had histological evidence of chronic salpingitis. CONCLUSIONS: The study suggests that PID may not be the only cause of perihepatic adhesions.