Treatment of Male Sexual Partners of Women With Bacterial Vaginosis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: We aimed to determine if treatment of male sexual partners of women with recurrent bacterial vaginosis (BV) with oral metronidazole 2×/day for 7 days (ie, multidose metronidazole) significantly decreased BV recurrence rates in the female. METHODS: This was a multicenter, 2-arm, double-blind, placebo-controlled study. Women with recurrent BV and current diagnosis of BV by Amsel and Nugent were enrolled. Multidose metronidazole for 7 days was dispensed to women. Male partners were randomized to placebo versus multidose metronidazole for 7 days and asked to refrain from unprotected sex for 14 days. Female follow-up visits were conducted at day 21 and 8 and 16 weeks. Male follow-up visits occurred at days 14-21. BV cure was defined as 0-2 Amsel criteria and Nugent score 0-6 in the female partner with the primary endpoint at 16 weeks. RESULTS: 214 couples were enrolled. In the intent-to-treat population, there was no significant difference between treatment arms for the primary outcome. BV treatment failure occurred in 81% and 80% of women in the metronidazole and placebo arms through the third follow-up visit, respectively (P > .999). However, women whose male partners adhered to study medication were less likely to fail treatment (adjusted relative risk, .85; 95% CI, .73-.99; P = .035). This finding persisted in post hoc comparisons in the metronidazole arm. CONCLUSIONS: Overall, this study did not find that male partner treatment with multidose metronidazole significantly reduces BV recurrence in female partners, although women whose partners adhered to multidose metronidazole were less likely to fail treatment. CLINICAL TRIALS REGISTRATION: (NCT02209519).

Conventional oral and secondary high dose vaginal metronidazole therapy for recurrent bacterial vaginosis: clinical outcomes, impacts of sex and menses.

PURPOSE: Oral metronidazole therapy is the standard of care for bacterial vaginosis (BV), yet it has alarming rates of recurrence and refractory responses among recurrent BV (RBV) patients. This study addresses whether high dose vaginal metronidazole therapy (HDM) is beneficial in RBV patients who fail after standard of care (SOC) therapy, whether diagnostic test scores proximal to the HDM predict clinical outcome, and whether menses, coitus, or race influences therapy outcome. PATIENTS AND METHODS: A total of 90 patients with RBV were given SOC and tracked 74 for up to 9 months. Refractory or recurrent patients (57) with symptomatic BV were given HDM and followed for up to 8 months. Patients were evaluated by Amsel criteria, Nugent score, and a qPCR assay that assesses the Lactobacillus content. RESULTS: HDM achieved at least short-term remission in 68% of the patients who were refractory to or recurred after SOC and provided a 10-day increase in the mean duration of remission among patients who eventually recurred (p=0.027). Patients with prolonged dysbiosis (pH >5 or Amsel 4) before symptomatic recurrence were more likely to recur after subsequent HDM. Most recurrence happened within 10 days of menses, but sex in this cohort was not associated with clinical outcome. Mean diagnostic BV scores of African American patients in remission were inferior to scores of a small cohort of Caucasian patients in remission. CONCLUSION: Encouraging results obtained with HDM justify a prospective, randomized study to determine if follow-up HDM is beneficial among a broader cohort of women failing conventional oral metronidazole therapy.

Prognostic Indicators of Recurrence of Bacterial Vaginosis.

Following all forms of therapy for bacterial vaginosis (BV), recurrence rates are extremely high. Many diagnostic tests are available that differentiate bacterial vaginosis from other types of vaginal disorders, but none predict recurrence after treatment, nor are any vetted for monitoring ongoing responses to treatment. Our goal was to determine which tests, and at what optimal times, have prognostic value in predicting recurrence. This prospective cohort study monitored 74 highly recurrent BV patients for up to 9 months. Symptomatic BV patients were treated with oral metronidazole and were evaluated at cessation of treatment and monthly. Index tests included Amsel, Nugent, BV Blue, and Affirm VPIII, as well as a quantitative PCR (qPCR)-based test under initial evaluation here. The qPCR-based LbRC ( LactobacillusRelative Composition) assay predicted BV recurrence when performed shortly after oral metronidazole treatment, with both 90% positive predictive values (PPV) and 74% negative predictive values (NPV); the Nugent scores had 93% PPV but poor NPV (57%). No test, at any other visit, was prognostic. The LbRC assay and, to a lesser extent, Nugent tests scored a week after oral metronidiazole predicted recurrence, suggesting that the recurrence in this cohort was predominantly by relapse due to incomplete restoration of eubiosis soon after therapy. This is the first study in an under evaluated population of recurrent BV patients that emphasizes the need for and a pathway to a possible prognostic modality. Given the high recurrence rates of BV, prognostic tests that could influence individualized treatment alternatives are urgently needed.

Development and Validation of a Highly Accurate Quantitative Real-Time PCR Assay for Diagnosis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most common gynecological infection in the United States. Diagnosis based on Amsel's criteria can be challenging and can be aided by laboratory-based testing. A standard method for diagnosis in research studies is enumeration of bacterial morphotypes of a Gram-stained vaginal smear (i.e., Nugent scoring). However, this technique is subjective, requires specialized training, and is not widely available. Therefore, a highly accurate molecular assay for the diagnosis of BV would be of great utility. We analyzed 385 vaginal specimens collected prospectively from subjects who were evaluated for BV by clinical signs and Nugent scoring. We analyzed quantitative real-time PCR (qPCR) assays on DNA extracted from these specimens to quantify nine organisms associated with vaginal health or disease:Gardnerella vaginalis,Atopobium vaginae, BV-associated bacteria 2 (BVAB2, an uncultured member of the orderClostridiales),Megasphaeraphylotype 1 or 2,Lactobacillus iners,Lactobacillus crispatus,Lactobacillus gasseri, andLactobacillus jensenii We generated a logistic regression model that identifiedG. vaginalis,A. vaginae, andMegasphaeraphylotypes 1 and 2 as the organisms for which quantification provided the most accurate diagnosis of symptomatic BV, as defined by Amsel's criteria and Nugent scoring, with 92% sensitivity, 95% specificity, 94% positive predictive value, and 94% negative predictive value. The inclusion ofLactobacillusspp. did not contribute sufficiently to the quantitative model for symptomatic BV detection. This molecular assay is a highly accurate laboratory tool to assist in the diagnosis of symptomatic BV.

Successful laparoscopic management of ruptured tubal pregnancy with an ipsilateral ectopic pelvic kidney.

Objective. To report a case of successful laparoscopic management of a left ruptured tubal pregnancy in the setting of an ipsilateral ectopic pelvic kidney. Method. Case report was prepared at Wayne State University/Detroit Medical Center. The patient is a young woman gravida 2 para 0 in her twenties who presented with severe abdominal pain and vaginal bleeding. She had a plateaued beta HCG and ultrasonographic findings suggestive of ectopic left tubal pregnancy along with an ectopic ipsilateral pelvic kidney. The IRB approval is not needed, as this is a case report. The informed consent could not be obtained, as the patient was not reachable. Result. Multiple intraperitoneal adhesions, left ruptured ampullary ectopic pregnancy and left retroperitoneal pelvic mass consistent with ipsilateral ectopic pelvic kidney. Conclusion. Laparoscopic management of tubal pregnancy can be safely performed in the setting of an ipsilateral ectopic pelvic kidney.

High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

High-dose vaginal metronidazole for recurrent bacterial vaginosis--a pilot study.

OBJECTIVE: The purpose of this study was to evaluate high-dose intravaginal metronidazole, with or without miconazole, in enhancing cure rates in women with recurrent BV. MATERIALS AND METHODS: A total of 43 women with symptomatic recurrent BV were enrolled in a 4-arm study comparing 500 mg versus 750 mg of metronidazole, with or without miconazole, intravaginally for 7 days. Test of cure by saline wet mount and 10% potassium chloride microscopy, pH, Gram stain for Nugent score, and yeast culture were performed 3 times after treatment: 3 to 7 days, 30 to 35 days, and 60 to 70 days. RESULTS: Overall cure rate for the entire group was 92.6% at visit 2, 62.1% at visit 3, and 51.4% at visit 4. At visit 2, there was no difference in cure rates among patients who received metronidazole 750 mg ± miconazole daily (90.5%) compared with metronidazole 500 mg ± miconazole daily (85%). At visit 3, there was a significant improvement in cure rates among patients who received metronidazole 750 mg ± miconazole daily (78.9%) compared with metronidazole 500 mg ± miconazole daily (44.4%) (p < .05). At visit 4, a significant difference in clinical cure rates persisted among patients who received metronidazole 750 mg ± miconazole daily (68.4%) compared with of metronidazole 500 mg ± miconazole daily (33.3%; p < .05). Poor responses (Nugent score > 4 or pH > 4.4) at the first visit alter treatment-predicted recurrence. The addition of miconazole did not enhance BV response rates. CONCLUSIONS: Cure rates for BV were high in this refractory cohort and seemed dose dependent.

Does cerclage improve neonatal outcomes in a molar pregnancy and a coexistent fetus? A case report.

BACKGROUND: Complete hydatiform mole and coexistent viable fetus is very rare. The use of a cervical cerclage for cervical indications in the presence of this condition has never been reported. Although the diagnosis was made postnatal, the objective is to present a case with good neonatal outcome. CASE PRESENTATION: A patient presented with vaginal spotting around 23 weeks. She has a history of four preterm deliveries. Her cervix was dilated and a cerclage was placed. She presented again with PPROM around 25 weeks. She went into spontaneous preterm labor and delivered a viable fetus that is a healthy girl today. Eventually the pathology of the placenta showed a complete hydatidiform mole. CONCLUSION: It is necessary to inform patients about the potential risks and poor outcomes of this condition. For those who desire all potential interventions, cerclage placement could be considered.

Amniotic fluid inflammation with negative culture and outcome after cervical cerclage.

OBJECTIVE: To determine whether amniotic fluid (AF) inflammation, in the absence of infection, is associated with adverse pregnancy outcomes in nonelective cervical cerclage patients. METHODS: A retrospective case-control study was carried out. The patient population included 82 singleton pregnancies with negative AF cultures. The variables used to define AF inflammation were white blood cell count (WBC) >50 cell/mm(3), glucose <14 mg/dl or interleukin-6 (IL-6) >11.3 ng/ml. The study group consisted of cases with intra-amniotic inflammation. Sub-analysis was performed for the groups in which IL-6 concentrations were measured. Adverse outcomes were evaluated with variables such as gestational age at delivery, interval from cerclage to delivery, chorioamnionitis and cumulative neonatal morbidity. RESULTS: Elevated AF WBC was correlated with severe and extreme preterm delivery (p < 0.05). Decreased AF glucose was associated with histological chorioamnionitis and a decreased cerclage to delivery interval (p < 0.05). Elevated AF IL-6 correlated significantly with decreased gestational age at delivery (p < 0.012) and decreased cerclage to delivery interval (p < 0.001). Elevated IL-6 concentrations were associated with severe, extreme preterm delivery (p < 0.001) and neonatal death (p < 0.001). CONCLUSION: Elevated AF IL-6, elevated WBC and low AF glucose, in the absence of a positive AF culture, are significantly associated with adverse pregnancy outcomes in patients undergoing nonelective cerclage.