Treatment patterns and economic burden of bacterial vaginosis among commercially insured women in the USA.

Aim: Bacterial vaginosis (BV) is a common vaginal dysbiosis associated with adverse clinical sequelae, most notably, increased risk of sexually transmitted infections (STIs). The aims of this study were to estimate the frequency of BV recurrence, treatment patterns, other gynecological (GYN) conditions, and the associated healthcare resource utilization (HCRU) and costs among commercially insured patients in the USA. Patients & methods: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication (fungal treatment only excluded) were selected from the Merative™ MarketScan commercial database (2017-2020). During a minimum 12-month follow-up, additional treatment courses, treatment patterns, frequency of other GYN conditions, and HCRU and costs were assessed. Generalized linear models were used to identify baseline predictors of total all-cause healthcare costs and number of treatment courses. Results: The study population included 140,826 patients (mean age: 31.5 years) with an incident vaginitis diagnosis and ≥1 BV medication claim. During the follow-up, 64.2% had 1 treatment course, 22.0% had 2, 8.1% had 3, and 5.8% had ≥4; 35.8% had a BV recurrence (≥2 BV medication claims). The most commonly prescribed BV medication was oral metronidazole (73.6%). Approximately 12% (n = 16,619) of patients had a new diagnosis of another GYN condition in the follow-up; 8.2% had a new STI, which were more common among patients with ≥4 treatment courses (12.9%). During follow-up, total all-cause healthcare costs averaged $8987 per patient per year (PPPY) of which $470 was BV-related. BV-related healthcare costs increased from $403 PPPY among those with 1 treatment course to $806 PPPY among those with ≥4 with nearly half the costs attributed to outpatient office visits. Conclusion: BV recurrence among this population represented a substantial clinical and healthcare economic burden warranting improvements in women's healthcare.

[Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis].

This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

A Phase 1 pharmacokinetic study of a single-dose bioadhesive clindamycin 2% gel for bacterial vaginosis.

OBJECTIVES: To evaluate pharmacokinetics (PK) of a single dose of an investigational 2% clindamycin phosphate vaginal gel in healthy women by assessment of plasma and vaginal clindamycin concentrations over 7 days, and assess safety. METHODS: Single-centre, Phase 1, single-dose PK study. Blood and vaginal samples were collected daily and safety was evaluated through to Day 7. RESULTS: Twenty-one subjects were enrolled; 20 completed the study. Plasma clindamycin concentrations demonstrated quantifiable values in all subjects through to 24 h post-dose, remaining above the limits of quantification (LOQ) through to 48 h for the majority of subjects. Systemic exposure (AUC0-t) was 1179 (range 62-3822) h·ng/mL. Arithmetic mean AUC0-24 was 818 (range 51-3287) h·ng/mL. Vaginal clindamycin phosphate levels were relatively high 24 h following administration in 15/21 subjects (6 subjects had values >400 µg/g and 9 had values of 100-400 µg/g). The levels dropped in most participants to below the LOQ 2 days following dosing. In a few participants, levels remained elevated for several days. Maximal amounts of vaginal clindamycin occurred on Day 2 with a mean value of 30.3 µg. One treatment-emergent adverse event (TEAE) of moderate-severity headache not related to study drug was reported and resolved on Day 1. No TEAEs were related to physical examinations, pelvic examinations, laboratory values or vital signs. CONCLUSIONS: The vaginal concentrations of clindamycin phosphate plus the clindamycin plasma profile over time are consistent with release of drug from the investigational gel over 24 to 72 h. A single dose was well tolerated.

Secnidazole for Trichomoniasis in Women and Men.

INTRODUCTION: Secnidazole (SEC), newly FDA-approved for trichomoniasis, is a potent 5-nitroimidazole with selective toxicity against various infections. It has been used internationally to treat trichomoniasis, bacterial vaginosis, and other infections for decades. Trichomoniasis is the most common non-viral sexually transmitted infection worldwide and is associated with significant morbidity. In comparison to the only other approved treatments for trichomoniasis in the U.S.-metronidazole and tinidazole-SEC has favorable pharmacokinetics, including a longer half-life, and a lower minimal lethal concentration against Trichomonas vaginalis. OBJECTIVES: Provide an updated, comprehensive review of the literature evaluating SEC as a treatment for trichomoniasis in women and men. METHODS: We conducted a search to identify existing research on SEC and trichomoniasis. On August 6, 2021, we searched MEDLINE using the terms "secnidazole" and "trichomon.*" We excluded reviews, editorials, case reports, and small case series. RESULTS: We identified 29 articles; 14 of which were included: 5 reported in vitro pharmacologic data on SEC, 6 were observational studies, and 4 were controlled clinical trials (1 observational study also reported in vitro pharmacologic data). Six studies reported data on women only, 1 on men only, and 3 on women and men. These studies showed that SEC-as a single dose or 3-day course-had comparable efficacy to multi-dose metronidazole for treating trichomoniasis in women and men, was generally well tolerated by patients, and had a favorable pharmacokinetic profile. A single 2-g dose of SEC also led to a microbiologic cure rate of 92.2% in the first randomized, double-blind, placebo-controlled study of trichomonas-infected US-based women. CONCLUSION: SEC is an efficacious and safe treatment for women and men with trichomoniasis. Single-dose administration makes it a favorable treatment option for patients, especially in cases where adherence to other multi-dose treatment regimens could be problematic. Christina A. Muzny and Olivia T. Van Gerwen. Secnidazole for Trichomoniasis in Women and Men. Sex Med Rev 2022;10:255-262.

Hormonal Contraception and Vaginal Infections Among Couples Who Are Human Immunodeficiency Virus Serodiscordant in Lusaka, Zambia.

OBJECTIVE: To examine the relationship between hormonal contraception and vaginal infections with bacterial vaginosis, vaginal candidiasis, or trichomoniasis. METHODS: Couples who were human immunodeficiency virus (HIV) serodiscordant in Zambia were enrolled in a longitudinal cohort study. From 1994 to 2002, both partners were seen quarterly and received physical exams including genital examinations. Separate rates for three outcome infections of interest (bacterial vaginosis, vaginal candidiasis, and trichomoniasis) were calculated. Bivariate associations between baseline and time-varying covariates and outcome infections of interest were evaluated using unadjusted Anderson-Gill survival models. Adjusted hazard ratios (aHRs) were generated using multivariable Anderson-Gill survival models that included demographic and clinical factors associated with both hormonal contraceptive use and each infection of interest. RESULTS: There were 1,558 cases of bacterial vaginosis, 1,529 cases of vaginal candidiasis, and 574 cases of trichomoniasis over 2,143 person-years of observation. Depot medroxyprogesterone acetate (DMPA) users had significantly lower rates of trichomoniasis and bacterial vaginosis. In adjusted models, DMPA was protective for bacterial vaginosis (aHR=0.72; 95% CI 0.54-0.95), candidiasis (aHR 0.75, 95% CI 0.57-1.00) and trichomoniasis (aHR=0.43, 95% CI 0.25-0.74). Oral contraceptive pills were protective for candidiasis (aHR=0.79, 95% CI 0.65-0.97). CONCLUSION: We confirm that DMPA use was associated with reduced rates of the three most common causes of vaginitis, and oral contraceptive pill use was associated with reduced rates of candidiasis among women in couples who were HIV discordant.

The two-sided role of the vaginal microbiome in Chlamydia trachomatis and Mycoplasma genitalium pathogenesis.

Sexually transmitted infections (STI) can have major consequences for the reproductive health of women. Mycoplasma genitalium is a STI that is not as well studied but causes pelvic inflammatory disease (PID) among other complications. Another well-known STI is Chlamydia trachomatis, notorious for its capability to cause infertility. Both C. trachomatis and M. genitalium share some of the same clinical aspects. Parts of the pathogenesis of C. trachomatis and M. genitalium infections are unclear but potential factors are the microbiome and other STIs. The healthy vaginal microbiome is dominated by Lactobacillus spp; these bacteria protect the host against invading bacteria like C. trachomatis and M. genitalium by producing antibacterial compounds and providing a mechanical barrier. A dysbiosis of the vaginal microbiome is characterized by a non-Lactobacillus spp. dominated microbiome, also known as bacterial vaginosis (BV). BV and BV associated bacteria play a role in the pathogenesis of STIs such as C. trachomatis and M. genitalium. The different species of BV associated bacteria have distinct characteristics that could play a role in C. trachomatis and M. genitalium infections. Host factors should also be considered when analysing the interaction of C. trachomatis and M. genitalium and the microbiome. One important factor is the hormonal homeostasis. Oral hormonal contraception influences the vaginal milieu and could influence the infection process of STIs. Overall, this review attempts to give an overview of the pathogenesisof C. trachomatis and M. genitalium infections and the relationship between M. genitalium, C. trachomatis, and the vaginal microbiome.

The effect of antifungal treatment on the vaginal flora of women with vulvo-vaginal yeast infection with or without bacterial vaginosis.

Antibacterial therapy may enhance the risk of symptomatic vulvo-vaginal candidosis in susceptible women. We addressed the question whether oral antifungal treatment for vulvo-vaginal candidosis also influences the bacterial vaginal microflora. One hundred and forty-two patients with a culture-proven acute episode of recurrent vulvo-vaginal candidosis (RVC) were treated with fuconazole according to the ReCiDiF regimen (induction dose of 600 mg orally per week followed by 200 mg per week) or with a single dose of 200 mg pramiconazole, a new potent oral triazole. At inclusion, 1 week and 1 month after the end of antifungal treatment, the bacterial microflora was assessed by microscopy of vaginal fluid to detect lactobacillary grades and bacterial vaginosis (BV). The presence of BV was studied in these patients with vulvo-vaginal candidosis after treatment with antifungal medication. At the start of oral antifungal treatment, 6.3% of women with Candida were co-infected with BV. Of the BV-negative women, 10 out of 133 (8%) developed BV after 1 week and after 1 month 8 of them (7%) were still BV-positive. Although no patients received antibacterial treatment at any moment of the study, 6 out of 9 (66%) of the women with Candida and BV at inclusion no longer had BV 1 week after antifungal treatment and 6 out of 7 (86%) lacked BV after 1 month. Treatment with antifungals may have a beneficial effect on women with concurrent BV, but does not prevent BV from occurring in BV-negative women with Candida vaginitis.

The safety of candidate vaginal microbicides since nonoxynol-9: a systematic review of published studies.

OBJECTIVE: To gain a greater understanding of published safety data for candidate vaginal microbicides. DESIGN: A systematic review of human safety trials of candidate vaginal microbicides - agents designed to protect women against HIV and other sexually transmitted infections. METHODS: Trials were published in peer-reviewed journals, and publication cut-off was August week 4, 2008. Trials of nonoxynol-9 were excluded, as were trials without a control group, trials that enrolled only male participants or reported on the investigation of a product for the treatment of a genital infection. RESULTS: Twenty-one trials of 11 products, involving 1465 women, satisfied review criteria. Most trials reported on genital epithelial findings and urogenital symptoms and a number reported a range of other local and systemic toxicity endpoints. Trials were generally of short duration (2 weeks or less) with small sample sizes. There were few findings of significant difference between women in active and control arms. Among the products assessed in more than one study, there were significantly more genital findings with intact epithelium in recipients of PRO2000 [relative risk (RR) 1.68, 95% confidence interval (CI) 1.08-2.60] and a lower incidence of bacterial vaginosis in dextrin sulphate recipients (RR 0.61, 95% CI 0.42-0.88). CIs were generally very wide, and most studies were unable to exclude differences of a substantial magnitude between treated and control women. CONCLUSION: Larger and longer safety studies are necessary to detect clinically important toxicities, including those that indicate a potential increase in HIV risk, and provide assurance that agents are ready for large-scale effectiveness trials.

Changes in the vaginal flora after two percent clindamycin vaginal cream in women at high risk of spontaneous preterm birth.

OBJECTIVE: To analyse alterationS in the vaginal flora after 2% clindamycin vaginal cream or placebo administered for the prevention of preterm delivery in high risk women. DESIGN: Observational study during a randomised multicentre double-blind placebo controlled trial. SETTING: Twelve city hospitals in The Netherlands. PARTICIPANTS: One hundred and sixty-eight women were enrolled. Alterations in the vaginal flora could be analysed in one hundred and twenty-four women by comparing the Nugent score on entry to the trial and at 31 weeks' gestation. The Nugent score was classified into normal, intermediate and bacterial vaginosis. INTERVENTIONS: Two percent clindamycin vaginal cream or placebo cream administered daily for seven days at week 26 of pregnancy. MAIN OUTCOME: Changes in the vaginal flora at week 31 of pregnancy. RESULTS: The placebo group consisted of 64 women and the clindamycin group of 60 women. At week 31 the vaginal flora was similar to week 26 with placebo cream but changed from normal vaginal flora to intermediate or bacterial vaginosis with 2% clindamycin vaginal cream. CONCLUSION: Obstetricians should not prescribe 2% clindamycin vaginal cream to pregnant women with normal vaginal flora in order to reduce the incidence of preterm birth. because it has no beneficial effects and is actually harmful. 2% Clindamycin vaginal cream encourages the presence of bacterial vaginosis which is epidemiologically associated with preterm birth.

Induction of vaginal Lactobacillus phages by the cigarette smoke chemical benzo[a]pyrene diol epoxide.

Because smoking increases a woman's risk of contracting bacterial vaginosis (BV), which is manifested by a reduction of vaginal lactobacilli and an overgrowth of anaerobic bacteria, chemicals contained in cigarette smoke were analyzed in vitro to determine their role in reducing lactobacilli. The result showed that trace amounts of benzo[a]pyrene diol epoxide (BPDE), which can be found in vaginal secretion of women who smoke, significantly increased phage induction in lactobacilli. This finding implies that smoking may reduce vaginal lactobacilli by promoting phage induction.

Cephadroxil promotes vaginal colonization with Escherichia coli.

The aim of this study was to examine whether a vaginal Escherichia coli colonization, mimicking the one seen in UTI-prone females, could be induced by local cephadroxil administration. When five adult cynomolgus monkeys were given a vaginal flush with a P-fimbriated E. coli strain, none became persistently colonized. When such colonization attempts were preceded by cephadroxil administration a persistent colonization occurred in 9/10 experiments. Cephadroxil also promoted a spread of fecal E. coli strains to the vagina. Reduction of the anaerobic vaginal flora can explain the breakdown of the colonization resistance. Clinical observations suggest that accumulation of E. coli around the urethral orifice increases the risk of UTI. Therefore antibiotics which promote such colonization may increase the risk for UTI in susceptible patients. From this point of view antibiotics such as cephadroxil may be less suitable for treatment of UTI-susceptible patients.