Peripartum Uterine Clostridial Myonecrosis: A Report of Two Fatal Cases.

INTRODUCTION: Uterine clostridial myonecrosis is a rare infection associated with a high mortality rate. This report presents 2 cases of maternal mortality resulting from peripartum clostridial myonecrosis of the uterus. CASE PRESENTATION: Case 1 is a 30-year-old woman (nullipara) who presented in labor at term with an intra-amniotic infection and fetal demise. She rapidly developed septic shock, and cesarean hysterectomy was performed for a suspected necrotizing uterine infection later identified to be Clostridium septicum. Case 2 is an adolescent who presented in septic shock following first trimester medication abortion and died during emergent exploratory laparotomy; cultures grew Clostridium sordellii. Both patients expired within 18 hours of hospital admission. DISCUSSION: Given the rapidly progressive course of clostridial infections, maintaining a high index of suspicion is imperative for ensuring timely diagnosis and effective treatment. Prompt recognition of clinical features associated with clostridial myonecrosis - abdominal pain, tachycardia, leukocytosis and hyponatremia - is essential in preventing mortality. The utilization of point-of-care ultrasound may expedite the diagnosis of uterine myonecrosis. When uterine myonecrosis is suspected, immediate initiation of penicillin-based antibiotics, alongside clindamycin, and aggressive surgical intervention including hysterectomy are essential for ensuring survival. Although the decision to perform a hysterectomy can be challenging, especially in cases involving child-bearing-aged patients, it is a vital step to avert a fatal outcome. CONCLUSIONS: By presenting these cases, we aim to raise awareness of this uncommon, but highly lethal infection to expedite diagnosis and treatment to improve patient outcomes.

Localized Provoked Vulvodynia-An Ignored Vulvar Pain Syndrome.

Localized provoked vulvodynia (LPV) causes dyspareunia among reproductive aged women. We review the pathogenesis of LPV and suggest that LPV is an inflammatory pain syndrome of the vestibular mucosa triggered by microbial antigens in a susceptible host. Tissue inflammation and hyperinnervation are characteristic findings which explain symptoms and clinical signs. Education of health care providers of LPV is important since this condition is common, often unrecognized, and patients often become frustrated users of health care. Research is needed on the antigen triggers of the syndrome. Randomized clinical trials are needed to evaluate treatment modalities.

Diagnosis and Management of Vulvovaginal Lichen Planus.

IMPORTANCE: Genital lichen planus is a debilitating disorder that lacks definitive recommendations regarding diagnosis and treatment. OBJECTIVE: The aim of this study was to present best practices from available evidence for the diagnosis and treatment of genital lichen planus. EVIDENCE ACQUISITION: We conducted a narrative review of the literature on genital lichen planus by searching PubMed using the following search terms: "vulvar lichen planus" OR (vulvar diseases[mesh] OR vulva[mesh]) AND lichen planus[mesh] OR vulvar[ti] AND "lichen planus"[ti]. We included all languages and years in the search. RESULTS: The search resulted in 273 citations that we reviewed for relevancy and selected 60 as the foundation for this review that focuses on genital sites. Diagnosis can be made without biopsy, and when a biopsy is taken, the pathologic findings may be nonspecific. Topical ultrapotent corticosteroids are most commonly used as first-line treatment of genital lichen planus. CONCLUSIONS AND RELEVANCE: When patients present with genital lichen planus, a complete review of systems and a thorough physical examination should be performed because of the prevalence of extragenital sites. Treatment of genital disease should start with a topical, ultrapotent steroid, and follow-up visits should occur to ensure improvement and to monitor for adverse drug reactions and malignancy.

High Prevalence of Sexual Dysfunction in a Vulvovaginal Specialty Clinic.

OBJECTIVE: Our study evaluated the presence and predictors of sexual dysfunction in a vulvovaginal specialty clinic population. MATERIALS AND METHODS: Women who presented to a vulvovaginal specialty clinic were eligible to enroll. The participants completed a questionnaire, including Female Sexual Function Index to assess sexual dysfunction and Patient Health Questionnaire (PHQ)-9 depression screen, and underwent a standardized physical examination, with vaginal swabs collected for wet mount and culture. Logistic regression assessed the relationship between sexual dysfunction and clinical diagnosis. RESULTS: We enrolled 161 women, aged 18 to 80 years (median, 36 years), presenting with vulvovaginal complaints. Median symptom duration was 24 months; 131 women (81%) reported chronic symptoms (≥12 months). By PHQ-9, 28 women (17%) met depression criteria. In the month before assessment, 86 women (53%) experienced sexual dysfunction. Women had a primary diagnosis of vaginitis (n = 46 [29%]), vestibulodynia/vulvitis (n = 70 [43%]), lichen planus or lichen sclerosus (n = 24 [15%]). Controlling for age, we found that sexual dysfunction did not correlate with chronic symptoms (incidence rate ratio [IRR], 0.86; 95% confidence interval [CI], 0.50-1.48), depression (IRR, 1.24; 95% CI, 0.59-2.58), or presence of any of the 3 main diagnoses (IRR, 1.16; 95% CI, 0.47-2.88). DISCUSSION: Sexual dysfunction is present in more than half of women presenting to a vulvovaginitis referral clinic, more than twice the rate in the wider population.

Treating spontaneous and induced septic abortions.

Worldwide, abortion accounts for approximately 14% of pregnancy-related deaths, and septic abortion is a major cause of the deaths from abortion. Today, septic abortion is an uncommon event in the United States. The most critical treatment of septic abortion remains the prompt removal of infected tissue. Antibiotic administration and fluid resuscitation provide necessary secondary levels of treatment. Most young physicians have never treated septic abortion. Many obstetrician-gynecologists experience, or plan to experience, global health activities and will likely care for women with septic abortion. Thus, updated knowledge of the pathophysiology, clinical presentation, microbes, and proper treatment is needed to optimally treat this emergency condition when it exists. The pathophysiology of septic abortion involves infection of the placenta, especially the maternal villous space that leads to a high frequency of bacteremia. Symptoms and signs range from mild to severe. The microbes involved are usually common vaginal bacteria, including anaerobes, but occasionally potentially very serious and lethal infection is caused by bacteria that produce toxins. The primary treatment is early curettage to remove infected and devitalized tissue even in the face of continued fetal heart tones. Important secondary treatments are the administration of fluids and antibiotics. Updated references of sepsis and septic shock are reviewed.

Identification of a gene in Mycoplasma hominis associated with preterm birth and microbial burden in intraamniotic infection.

OBJECTIVE: Microbial invasion of the amniotic cavity is associated with spontaneous preterm labor and adverse pregnancy outcome, and Mycoplasma hominis often is present. However, the pathogenic process by which M hominis invades the amniotic cavity and gestational tissues, often resulting in chorioamnionitis and preterm birth, remains unknown. We hypothesized that strains of M hominis vary genetically with regards to their potential to invade and colonize the amniotic cavity and placenta. STUDY DESIGN: We sequenced the entire genomes of 2 amniotic fluid isolates and a placental isolate of M hominis from pregnancies that resulted in preterm births and compared them with the previously sequenced genome of the type strain PG21. We identified genes that were specific to the amniotic fluid/placental isolates. We then determined the microbial burden and the presence of these genes in another set of subjects from whom samples of amniotic fluid had been collected and were positive for M hominis. RESULTS: We identified 2 genes that encode surface-located membrane proteins (Lmp1 and Lmp-like) in the sequenced amniotic fluid/placental isolates that were truncated severely in PG21. We also identified, for the first time, a microbial gene of unknown function that is referred to in this study as gene of interest C that was associated significantly with bacterial burden in amniotic fluid and the risk of preterm delivery in patients with preterm labor. CONCLUSION: A gene in M hominis was identified that is associated significantly with colonization and/or infection of the upper reproductive tract during pregnancy and with preterm birth.

Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women.

OBJECTIVE: The objective of the study was to evaluate the upper genital tract (UGT) presence of vaginal bacterial species using sensitive molecular methods capable of detecting fastidious bacterial vaginosis (BV)-associated bacteria. STUDY DESIGN: Vaginal swabs were collected prior to hysterectomy. The excised uterus was sterilely opened and swabs collected from the endometrium and upper endocervix. DNA was tested in 11 quantitative polymerase chain reaction (PCR) assays for 12 bacterial species: Lactobacillus iners, L crispatus, L jensenii, Gardnerella vaginalis, Atopobium vaginae, Megasphaera spp, Prevotella spp, Leptotrichia/Sneathia, BVAB1, BVAB2, BVAB3, and a broad-range16S ribosomal ribonucleic acid gene assay. Endometrial fluid was tested with Luminex and an enzyme-linked immunosorbent assay for cytokines and defensins and tissue for gene expression of defensins and cathelicidin. RESULTS: We enrolled 58 women: mean aged 43±7 years, mostly white (n=46; 79%) and BV negative (n=43; 74%). By species-specific quantitative PCR, 55 (95%) had UGT colonization with at least 1 species (n=52) or were positive by 16S PCR (n=3). The most common species were L iners (45% UGT, 61% vagina), Prevotella spp (33% UGT, 76% vagina) and L crispatus (33% UGT, 56% vagina). Median quantities of bacteria in the UGT were lower than vaginal levels by 2-4 log10 ribosomal ribonucleic acid gene copies per swab. There were no differences in the endometrial inflammatory markers between women with no bacteria, Lactobacillus only, or any BV-associated species in the UGT. CONCLUSION: Our data suggest that the endometrial cavity is not sterile in most women undergoing hysterectomy and that the presence of low levels of bacteria in the uterus is not associated with significant inflammation.

Synergy and interactions among biological pathways leading to preterm premature rupture of membranes.

Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. Impact of PPROM is greatest in low- and middle-income countries where prematurity-related deaths are most common. Recent investigations identify cytokine and matrix metalloproteinase activation, oxidative stress, and apoptosis as primary pathways to PPROM. These biological processes are initiated by heterogeneous etiologies including infection/inflammation, placental bleeding, uterine overdistention, and genetic polymorphisms. We hypothesize that pathways to PPROM overlap and act synergistically to weaken membranes. We focus our discussion on membrane composition and strength, pathways linking risk factors to membrane weakening, and future research directions to reduce the global burden of PPROM.

Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) has been linked to human immunodeficiency virus type 1 (HIV-1) acquisition. METHODS: Vaginal microbiota of women using DMPA for up to 2 years were cultured. Mucosal immune cell populations were measured by immunohistological staining. RESULTS: Over 12 months, the proportion with H2O2-positive lactobacilli decreased (n = 32; 53% vs 27%; P = .03). Median vaginal CD3(+) cells also decreased (n = 15; 355 vs 237 cells/mm(2); P = .03), as did CD3(+)CCR5(+) cells (195 vs 128 cells/mm(2); P = .04), HLA-DR(+) cells (130 vs 96 cells/mm(2); P = .27), and HLA-DR(+)CCR5(+) cells (18 vs 10 cells/mm(2); P = .33). CONCLUSIONS: DMPA contraception does not increase vaginal mucosal CCR5(+) HIV target cells but does decrease CD3(+) T lymphocytes and vaginal H2O2-producing lactobacilli.

Group A streptococcal infections in obstetrics and gynecology.

Group A streptococcal (GAS) infections continue to be an infrequent, but potentially lethal infections in women despite the victory over childbed fever in the 1800s. Invasive group A streptococcal infection still causes 40% of septic deaths among patients with postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome. Many times symptoms and signs of this infection are nonspecific, but laboratory evaluation can suggest serious infection. The prudent combination of antibiotic and surgical therapy can be lifesaving.

A standardized template for clinical studies in preterm birth.

BACKGROUND: Preterm birth is a major societal and economic problem accounting for 80 to 90% of neonatal morbidity and mortality worldwide. It is recognized as a complex multifactorial condition comprising several distinct clinical phenotypes with different underlying etiologies. As animal models are expensive and fail to mimic the biology of spontaneous preterm birth in humans, understanding the pathophysiology requires detailed clinical studies. Meta-analyses and clinical translation of data, however, are limited by heterogeneity of study design and size, publication and reporting biases, definition of patient groups, and a lack of standard universal definitions. This article provides a harmonized open-source template for designing clinical studies addressing preterm birth. METHODS: Recommendations are made for clinical definitions, choice and assignment to preterm birth phenotypes, selection of enriched populations and control pregnancies, and potential confounding factors. In addition, recommendations are made for study design, sample size and power calculations, the minimal data sets needed for any study of preterm birth, and the optimal data set of an ideal study. RESULTS: Recommended patient phenotypes are infection, uterine overdistension, hemorrhage, stress (either maternal or fetal), and idiopathic. Confounding factors include medical conditions, obesity, antenatal glucocorticoids, multifetal pregnancies, and fetal sex. Guidelines regarding study design, sample size, and clinical data acquisition are provided to serve as a universal template for preterm birth studies. CONCLUSIONS: Adoption of a harmonized template will allow generation of protocols and studies with a basic degree of compatibility and will allow data to be compared, and samples and data sets to be combined for meaningful meta-analyses.

The emergence of Clostridium difficile infection among peripartum women: a case-control study of a C. difficile outbreak on an obstetrical service.

OBJECTIVE: An outbreak of 20 peripartum Clostridium difficile infections (CDI) occurred on the obstetrical service at the University of Washington Medical Center (UWMC) between April 2006 and June 2007. In this report, we characterize the clinical manifestations, describe interventions that appeared to reduce CDI, and determine potential risk factors for peripartum CDI. METHODS: An investigation was initiated after the first three peripartum CDI cases. Based on the findings, enhanced infection control measures and a modified antibiotic regimen were implemented. We conducted a case-control study of peripartum cases and unmatched controls. RESULTS: During the outbreak, there was an overall incidence of 7.5 CDI cases per 1000 deliveries. Peripartum CDI infection compared to controls was significantly associated with cesarean delivery (70% versus 34%; P=0.03), antibiotic use (95% versus 56%; P=0.001), chorioamnionitis (35% versus 5%; P=0.001), and the use of the combination of ampicillin, gentamicin, and clindamycin (50% versus 3%; P<0.001). Use of combination antibiotics remained a significant independent risk factor for CDI in the multivariate analysis. CONCLUSIONS: The outbreak was reduced after the implementation of multiple infection control measures and modification of antibiotic use. However, sporadic CDI continued for 8 months after these measures slowed the outbreak. Peripartum women appear to be another population susceptible to CDI.

Determinants of condom use among female sex workers in Kenya: a case-crossover analysis.

BACKGROUND: We evaluated predictors of consistent condom use among female sex workers (FSWs), a core group for controlling the spread of HIV. METHODS: In an analysis of data collected in 2004-2005 from 140 Kenyan FSWs who completed questionnaires administered during a baseline study visit and three bimonthly follow-up visits, we used a case-crossover design to identify predictors of consistent condom use during all coital acts in the preceding 2 weeks, overall and by partner type. RESULTS: Participants (n=140) completed the baseline visit and 390 bimonthly follow-up visits. Alcohol use during sex was negatively associated with consistent condom use with helping partners (defined as regular sex partners to whom the woman could go for help or support if needed) (adjusted odds ratio [AOR], 2.6, 95% confidence interval [CI] 1.0-6.5) but not associated with condom use with other partners. Coital frequency was associated with condom use with other partners only. Women who reported 1-5 (AOR 11.0, 95% CI 4.3-28.3) or 6-9 recent coital acts (AOR 3.8, 95% CI 1.7-8.8) with other partners were more likely to report consistent condom use with those partners than were women who reported ≥10 acts. Having a recent partner delay payment was inversely associated with consistent condom use with helping, other, or all partners. CONCLUSIONS: Correlates of consistent condom use differed by partner type. By using a case-crossover design, we were able to identify potentially modifiable factors associated with consistent condom use by FSWs who used condoms consistently with a given partner type during some periods but not others.

Assessment of changes in condom use among female sex workers in a prospective cohort study introducing diaphragm use for disease prevention.

Changes in the rates of condom use and number of sexual partners were evaluated among 140 female sex workers in Kibera, Kenya, participating in a 6-month study of diaphragm safety and acceptability for prevention of sexually transmitted infections conducted in 2004-2005. Analyses were stratified by partner type. Multivariable Tobit regression modeling was used to assess the association between study visit and proportion of acts protected. Participants completed 140 baseline visits and 390 bimonthly follow-up visits. The mean percentage of coital acts reported as protected by a condom increased from 56% at baseline to 68% at the 6-month visit (P < 0.01). Similar increases were observed for condom use by all partner types. Additionally, the mean number of sexual partners decreased over the study. Furthermore, consistent (i.e., 100%) diaphragm use during follow-up was associated with a higher proportion of coital acts protected by a condom in analyses adjusted for study visit and coital frequency. These findings suggest that, despite concerns that introduction of the diaphragm would result in more risky sexual behaviors, reported condom use increased and number of partners decreased.

Diaphragm for STI and HIV prevention: is it a safe method for women at high risk?

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).

Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid.

OBJECTIVE: We analyzed the vaginal fluid proteome to identify biomarkers of intraamniotic infection among women in preterm labor. STUDY DESIGN: Proteome analysis was performed on vaginal fluid specimens from women with preterm labor, using multidimensional liquid chromatography, tandem mass spectrometry, and label-free quantification. Enzyme immunoassays were used to quantify candidate proteins. Classification accuracy for intraamniotic infection (positive amniotic fluid bacterial culture and/or interleukin-6 >2 ng/mL) was evaluated using receiver-operator characteristic curves obtained by logistic regression. RESULTS: Of 170 subjects, 30 (18%) had intraamniotic infection. Vaginal fluid proteome analysis revealed 338 unique proteins. Label-free quantification identified 15 proteins differentially expressed in intraamniotic infection, including acute-phase reactants, immune modulators, high-abundance amniotic fluid proteins and extracellular matrix-signaling factors; these findings were confirmed by enzyme immunoassay. A multi-analyte algorithm showed accurate classification of intraamniotic infection. CONCLUSION: Vaginal fluid proteome analyses identified proteins capable of discriminating between patients with and without intraamniotic infection.