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Background: Bacterial vaginosis (BV) is difficult to eradicate due to BV biofilms protecting BV bacteria (Gardnerella, Prevotella, and other genera). With the growing understanding of biofilms, we systematically reviewed the current knowledge on the efficacy of anti-BV biofilm agents., Methods: We searched literature in the Scopus, Medline, and Embase databases for empirical studies investigating substances for the treatment of BV biofilms or prevention of their recurrence and their efficacy and/or safety., Results: Of 201 unique titles, 35 satisfied the inclusion criteria. Most studies (89%) reported on preclinical laboratory research on the efficacy of experimental antibiofilm agents (80%) rather than their safety. Over 50% were published within the past 5 years. Agents were classified into 7 groups: antibiotics, antiseptics, cationic peptides, enzymes, plant extracts, probiotics, and surfactants/surfactant components. Enzymes and probiotics were most commonly investigated. Earlier reports of antibiotics having anti-BV biofilm activity have not been confirmed. Some compounds from other classes demonstrated promising anti-BV biofilm efficacy in early studies., Conclusions: Further research is anticipated on successful antibiofilm agents. If confirmed as effective and safe in human clinical trials, they may offer a breakthrough in BV treatment. With rising antibiotic resistance, antibiofilm agents will significantly improve the current standard of care for BV management., Competing Interests: Potential conflicts of interest. J. M. and G. W. previously shared research grants covering biofilm-related infections, and both have research agreements with The University of Sydney. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: The present study is a single-centre, randomized, controlled clinical trial aimed to evaluate the effectiveness of the probiotic Lacticaseibacillus rhamnosus TOM 22.8 (DSM 33500) strain, orally administrated, to treat vaginal dysbiosis., Methods and Results: Overall, 80 women, with signs and symptoms of vaginal dysbiosis, were enrolled and allocated to the treatment group (A, n=60), who took 1 capsule of the probiotic strain for 10 consecutive days, or the non-treatment group (B, n=20), who did not receive any treatment. Clinical (vaginal signs and symptoms; pH of the vaginal fluid; Amsel criteria; Nugent score; Lactobacillary grade) and microbiological examinations were performed at baseline (T0), 10 days (T1), and 30 (T2) days after the oral administration of the probiotic TOM 22.8 strain. The latter resulted in a restoration of the physiological pH, accompanied by remission or attenuation of clinical signs and symptoms as well as the improvement of the quality of life (QoL). Microbiological data revealed a significant reduction of potentially pathogenic bacteria., Conclusion: The administration of the L. rhamnosus TOM 22.8 probiotic strain could be proposed as an effective strategy for the treatment of vaginal dysbiosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Bacterial vaginosis (BV) is a common problem in primary care. BV symptoms often have a negative impact on patients' quality of life and may predispose to gynaecological problems. Some patients experience recurring episodes of BV. This study's objective is to identify possible factors that may be associated with BV recurrence and describe the characteristics of these patients and interventions performed by general practitioners., Methods: In this retrospective cohort study, we used data from a primary care registration network in the Netherlands in the period 2015-2020. We analysed differences between patients with recurrent BV and patients with a single episode of BV in terms of characteristics and interventions performed by general practitioners., Results: We found that patients with recently prescribed antibiotics, and a medical history of sexually transmitted infections and/or Candidiasis significantly more often presented with recurrent BV. Patients with recurrent BV had more remote consultations and less in-person consultations than single-episode patients. The reason for encounter was more often a request for medication. Regarding GPs' diagnostic and therapeutic interventions, microbiological tests were more frequently performed in recurrent BV patients. Moreover, most patients in both groups were prescribed oral metronidazole most frequently., Conclusions: Our findings might help GPs to better recognise patients at risk of recurrence. GPs could re-evaluate their approach to the diagnosis and treatment of recurrent BV, opting for in-person consultation and using standardised diagnostic criteria and microbiological testing in patients with recurrent complaints. Antibiotic use for other conditions in these patients may lead to new BV episodes., (© The Author(s) 2023. Published by Oxford University Press.)

Bacterial vaginosis, a type of vaginal inflammation, can be considered the main reason for abnormal discharges of the vagina and vaginal dysbiosis during reproductive years. Epidemiological investigations of females suffering from vaginitis demonstrated that at least 30% to 50% of all women had Bacterial vaginosis (BV). One of the fields of treatment is the use of probiotics, probiotics are commonly defined as viable microorganisms (yeasts or bacteria) that can positively affect the health of their hosts. They are used in foods, notably fermented milk products, and medicine-related products. The development of new probiotic strains is aimed at more active advantageous organisms. Lactobacillus species are the dominant bacteria in a normal vagina that can decrease the pH of the vagina by the production of lactic acid. A number of lactobacilli types can produce hydrogen peroxide as well. The presence of hydrogen peroxide-induced low pH can prevent the growth of several other microorganisms. The vaginal flora of BV cases can modify by replacing the Lactobacillus species with a high density of anaerobic bacteria (i.e. Mobiluncus sp. Bacteroides sp.), Mycoplasma hominis, and Gardnerella vaginalis. More vaginal infections are treated with medications, while there is a possibility of recurrence and chronic infection because of the adverse effects on the indigenous lactobacilli. Probiotics and prebiotics have shown capacities for optimizing, maintaining, and restoring the vaginal microflora. Therefore, biotherapeutics can offer alternative approaches to reduce infections of the vagina and thus promote consumers' health., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Bacterial vaginitis (BV) is a syndrome of increased vaginal discharge, fishy smelling leucorrhea, and itching and burning vulva caused by the microecological imbalance in the vagina induced by mixture of Gardnerella vaginalis (GV) and some anaerobic bacteria. Fenticonazole, an imidazole derivative and antimicrobial compound, has been demonstrated to exert effective therapeutic effects in mixed vaginitis. Accordingly, our study was designed to explore the potential role of fenticonazole in GV-infected BV mouse models. Female C57/BL6 mice were injected intraperitoneally with β-estradiol 3 days before and on the day of GV infection to maintain a pseudoestrus state. On the day of infection, mice were intravaginally inoculated with 20 µl of a suspension of GV (6 × 106 CFU/ml). Fenticonazole was administered as 2% vaginal cream (0.2 mg each mouse) by intravaginal application once a day for 3 days beginning the day of infection. At day 3 postinfection, the mice were sacrificed and vaginal washes were harvested. GV proliferation and Lactobacillus content were calculated in the vaginal lavage. Neutrophil counts in the vaginal lavage were observed through Pap staining. Myeloperoxidase (MPO) activity and proinflammatory cytokine (TNF-α, IL-1β, IL-6, iNOS, COX2, and NF-κB) levels in vaginal tissues were measured by ELISA and western blotting. Vaginal tissues were stained by hematoxylin and eosin (H&E) to examine the exfoliation of vaginal epithelial cells. GV infection increased GV proliferation and neutrophil counts but reduced Lactobacillus content in the vaginal lavage, as well as enhanced MPO activity, proinflammatory cytokine levels, and the exfoliation of vaginal epithelial cells in vaginal tissues of BV mouse models. However, administration of fenticonazole significantly ameliorated the above phenomena. Fenticonazole greatly improves the symptoms of GV-induced BV in mouse models., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Bacterial vaginosis (BV) treatment failures and recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy., Methods: Women with BV (Bronx, New York and Thika, Kenya) received 7 days of oral metronidazole at enrollment (day 0) and underwent genital tract sampling of microbiome (16S ribosomal RNA gene sequencing), transcriptome (RNAseq), and immune mediator concentrations on day 0, 15, and 35., Results: Bronx participants were more likely than Thika participants to clinically respond to metronidazole (19/20 vs 10/18, respectively, P = .0067) and by changes in microbiota composition and diversity. After dichotomizing the cohort into responders and nonresponders by change in α-diversity between day 35 and day 0, we identified that transcription differences associated with chemokine signaling (q = 0.002) and immune system process (q = 2.5 × 10-8) that differentiated responders from nonresponders were present at enrollment. Responders had significantly lower levels of CXCL9 in cervicovaginal lavage on day 0 (P < .007), and concentrations of CXCL9, CXCL10, and monocyte chemoattractant protein 1 increased significantly between day 0 and day 35 in responders vs nonresponders., Conclusions: Response to metronidazole is characterized by significant changes in chemokines and related transcripts, suggesting that treatments that promote these pathways may prove beneficial., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Although vaginal symptoms are common, diagnosis of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis (TV) is not standardized. Diagnostic approaches and appropriateness of treatment were evaluated for women with symptoms of vaginitis who were seeking care at community practice sites., Methods: Three hundred three symptomatic women, across 8 University of Pittsburgh Medical Center-affiliated clinics, were evaluated per standard office-based practice. Four of 5 vaginal swabs (1 cryopreserved) were collected for a US Food and Drug Administration-authorized nucleic acid amplification test (NAAT) for vaginitis/vaginosis diagnosis; Nugent scoring (BV); yeast culture (VVC); and a second NAAT (for TV). Two hundred ninety women had evaluable samples. Medical record extraction facilitated verification of treatments prescribed within 7 days of the index visit and return visit frequency within 90 days., Results: Women had a mean age of 29.4 ± 6.5 years, 90% were not pregnant, 79% were of white race, and 38% reported vaginitis treatment within the past month. Point-of-care tests, including vaginal pH (15%), potassium hydroxide/whiff (21%), and wet mount microscopy (17%), were rarely performed. Of the 170 women having a laboratory-diagnosed cause of vaginitis, 81 (47%) received 1 or more inappropriate prescriptions. Of the 120 women without BV, TV, or VVC, 41 (34%) were prescribed antibiotics and/or antifungals. Among women without infectious vaginitis, return visits for vaginitis symptoms were more common among women treated empirically compared to those not receiving treatment (9/41 vs 5/79, P = .02)., Conclusions: Within a community practice setting, 42% of women having vaginitis symptoms received inappropriate treatment. Women without infections who received empiric treatment were more likely have recurrent visits within 90 days., Clinical Trials Registration: NCT03151928., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

We characterized the composition and structure of the vaginal microbiota in a cohort of 149 women with genital Chlamydia trachomatis infection at baseline who were followed quarterly for 9 months after antibiotic treatment. At time of diagnosis, the vaginal microbiota was dominated by Lactobacillus iners or a diverse array of bacterial vaginosis-associated bacteria including Gardnerella vaginalis. Interestingly, L. iners-dominated communities were most common after azithromycin treatment (1 g monodose), consistent with the observed relative resistance of L. iners to azithromycin. Lactobacillus iners-dominated communities have been associated with increased risk of C. trachomatis infection, suggesting that the impact of antibiotic treatment on the vaginal microbiota could favor reinfections. These results provide support for the dual need to account for the potential perturbing effect(s) of antibiotic treatment on the vaginal microbiota, and to develop strategies to protect and restore optimal vaginal microbiota., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Antibiotic resistance and infection recurrence are critical issues in treating bacterial vaginosis, the most common vaginal disorder in women of reproductive age. Novel alternatives to traditional antibiotics, such as peptidomimetics, have the potential to address this challenge. Previously, two series of cationic amphiphiles (CAms) were developed with both hydrophilic head groups and non-polar domains, giving them the ability to self-assemble into supramolecular nanostructures with membrane-lytic properties. Those CAms were shown to be effective against biofilms of Gardnerella vaginalis while preserving the commensal microbiota. Two new series of CAms were designed with varying levels of flexibility between the hydrophilic head groups and the hydrophobic domains. Activities against the vaginal pathogen G. vaginalis ranged from 1.3 to 18.5 µM, while the tested vaginal lactobacilli were significantly more tolerant of CAms, with minimal inhibitory concentration values as high as 208 µM. Minimal biofilm bactericidal concentrations of the tested CAms ranged from 21.47 to <388.3 µM, and were lowest against resistant forms of G. vaginalis, while Lactobacillus biofilms were tolerant of concentrations ≥687 µM. Safety aspects of the CAms were also investigated, and they were found to be safe for use against vaginal ectocervical tissue., (© FEMS 2019.)

Background: Genital immunology is a key determinant of human immunodeficiency virus (HIV) susceptibility. Both factors are modulated by bacterial vaginosis (BV) and, to some extent, by Lactobacillus iners, the genital Lactobacillus spp. that predominates in African, Caribbean, and other Black (ACB) women. We conducted a clinical trial to assess the impact of oral metronidazole treatment on the genital immune parameters of HIV acquisition risks in Kenyan women with BV., Methods: The primary endpoint was ex vivo cervical CD4+ T-cell HIV susceptibility after 1 month; secondary endpoints included genital cytokine/chemokine levels, cervical immune cell populations, and the composition of the cervico-vaginal microbiota by 16S ribosomal RNA gene amplicon sequencing., Results: BV resolved (Nugent score ≤ 3) at 1 month in 20/45 participants, and cervical CD4+ T-cell HIV entry was moderately reduced in all participants, regardless of treatment outcome. Resolution of BV and reduced abundances of BV-associated gram-negative taxa correlated with reduced genital interleukin (IL)-1α/β. However, BV resolution and the concomitant colonization by Lactobacillus iners substantially increased several genital chemokines associated with HIV acquisition, including interferon-γ inducible protein (IP)-10, macrophage inflammatory protein (MIP)-3α, and monokine induced by gamma interferon (MIG). In an independent cohort of ACB women, most of whom were BV-free, vaginal chemokines were again closely linked with L. iners abundance, though not other Lactobacillus spp., Conclusions: BV treatment reduced genital CD4+ T-cell HIV susceptibility and IL-1 levels, but dramatically increased the genital chemokines that may enhance HIV susceptibility; the latter effect was related to the restoration of an Lactobacillus iners-dominated microbiota. Further studies are needed before treatment of asymptomatic BV can be recommended for HIV prevention in ACB communities., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present serious reproductive health risks and management challenges, with poor control attributed to survival of treatment-resistant biofilm communities. Boric acid is used in various regimens for non-albicans VVC and recurrent BV. We investigated safety and efficacy of a novel boric acid-based vaginal anti-infective with enhanced antibiofilm activity (TOL-463) in treating BV and VVC., Methods: In this phase 2 randomized, investigator-blinded trial conducted at 2 sexual health clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463 vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9-12; safety was assessed at TOC and day 21-30., Results: One hundred six participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval [CI], 41%-75%) for TOL-463 insert and 50% (95% CI, 31%-69%) for TOL-463 gel, and for VVC, 92% (95% CI, 67%-99%) for TOL-463 insert and 81% (95% CI, 57%-93%) for TOL-463 gel. Both products were safe and well tolerated with no secondary cases of VVC; vulvovaginal burning was the most common adverse event (9.6%)., Conclusions: TOL-463, especially in vaginal insert form, is effective and safe in treating BV and VVC. Future studies should assess the potential role of TOL-463 as a biofilm disrupter in enhancing likelihood of cure relative to approved therapies, reducing recurrence rates, and combined with traditional antimicrobials., Clinical Trials Registration: NCT02866227., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Evidence suggests that specific vaginal bacteria associated with bacterial vaginosis (BV) may increase the risk of adverse health outcomes in women. Among women participating in a randomized, double-blinded trial, we assessed the effect of periodic presumptive treatment (PPT) on detection of select vaginal bacteria., Methods: High-risk women from the United States and Kenya with a recent vaginal infection received intravaginal metronidazole 750 mg plus miconazole 200 mg or placebo for 5 consecutive nights each month for 12 months. Vaginal fluid specimens were collected via polyester/polyethylene terephthalate swabs every other month and tested for bacteria, using quantitative polymerase chain reaction (PCR) assays targeting the 16S ribosomal RNA gene. The effect of PPT on bacterium detection was assessed among all participants and stratified by country., Results: Of 234 women enrolled, 221 had specimens available for analysis. The proportion of follow-up visits with detectable quantities was lower in the PPT arm versus the placebo arm for the following bacteria: BVAB1, BVAB2, Atopobium vaginae, Leptotrichia/Sneathia, and Megasphaera. The magnitude of reductions was greater among Kenyan participants as compared to US participants., Conclusions: Use of monthly PPT for 1 year reduced colonization with several bacteria strongly associated with BV. The role of PPT to improve vaginal health should be considered, and efforts to improve the impact of PPT regimens are warranted., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Unlabelled: Bacterial vaginosis is a frequent dysbiosis, where the normal lactobacillus-dominated flora is replaced by an anaerob/aerob polymicrobial flora. Bacterial vaginosis increases the risk of acquiring sexually transmitted infections (STI) including the most frequent Chlamydia trachomatis infections. Intravaginal antiseptics are part of the bacterial vaginosis treatment, and ideally they should also inhibit the bacterial vaginosis-related STI. Therefore, we tested the antichlamydial activity of four antiseptics: iodine aqueous solution, povidone-iodine, chlorhexidine and borax. First, we measured the impact of antiseptics on the viability of the HeLa cervical epithelial cells, and calculated the maximum nontoxic concentrations. Next, we infected the cells with C. trachomatis preincubated for 1 h with the particular antiseptic. The chlamydial growth was measured by direct quantitative PCR (qPCR) of the infected cells. The minimal inhibitory concentrations (MIC) of chlorhexidine and povidone-iodine were 3·91 and 97 μg ml(-1) respectively; however, the MIC of chlorhexidine was close to its maximum nontoxic concentration. The iodine aqueous solution and the borax showed no antichlamydial activity. Our in vitro studies showed that chlorhexidine and particularly povidone-iodine are potentially able to limit the bacterial vaginosis-related C. trachomatis infection., Significance and Impact of the Study: We measured the antichlamydial effects of various antiseptics. These antiseptics are being used for the treatment of bacterial vaginosis, but their effect on the bacterial vaginosis-related sexually transmitted infections, particularly the most frequent Chlamydia trachomatis (C. trachomatis) infections has not been investigated. We showed that povidone-iodine (Betadine) inhibited the chlamydial growth in concentrations that was not toxic to the epithelial cells. We concluded that due to its additional antichlamydial effect, povidone-iodine could be a preferable antiseptic in bacterial vaginosis treatment., (© 2016 The Society for Applied Microbiology.)

Practitioners and patients alike widely recognize the limitations of current therapeutic approaches to the treatment of bacterial vaginosis (BV). Options remain extremely limited, and our inability to prevent the frequently, often relentless symptomatic recurrences of BV and to reduce serious sequelae such as preterm delivery, remains an acknowledged but unresolved shortcoming. Our incomplete understanding of the pathophysiology of this unique form of vaginal dysbiosis has been a significant impediment to developing optimal treatment and prevention approaches. New drugs have not been forthcoming and are not likely to be available in the immediate future; hence, reliance on the optimal use of available agents has become essential as improvised often unproven regimens are implemented. In this review, we will explore the limitations of currently recommended therapies, with a particular focus on the contribution of reinfection and pathogen persistence to BV recurrence, and the development of interventions that target these mechanisms. Ultimately, to achieve sustained cure and effectiveness against BV-associated sequelae, it is possible that we will need approaches that combine antimicrobials with biofilm-disrupting agents and partner treatments in those at risk of reinfection., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

This article summarizes the highlights of the expert technical consultation on bacterial vaginosis (BV), sponsored by the National Institute of Allergy and Infectious Disease and held in Washington, DC, on 8-9 April 2015. Many issues touched on in this article are discussed in much greater detail in the 6 preceding articles in this supplement to The Journal of Infectious Diseases There was a consensus among the meeting attendees concerning the most important research issues in the field: the pathogenesis of the syndrome, way to optimize treatment, and the relative roles of sexual transmission and endogenous infection in BV epidemiology. This article concludes with a listing of BV and genitourinary tract research priorities that were discussed and agreed on by attendees. The most important of these included better characterization of vaginal microbiome community state subtypes, application of advanced "-omic" technologies to improve understanding of BV pathogenesis, further investigation of the relationships between the male and female genitourinary tract microbiomes, and the development of new drugs for BV treatment., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Longitudinal studies have consistently found a significant association between bacterial vaginosis (BV) and acquisition of sexually transmitted diseases. However, there are limited prospective data to confirm these findings., Methods: We conducted a prospective, randomized, open-label trial of home screening and treatment of young women with asymptomatic BV who were also at high risk for sexually transmitted diseases. These women were screened every 2 months for 12 months and randomized to treatment with oral metronidazole 500 mg twice daily for 7 days or observation alone. The primary outcome was the incidence of gonorrhea and/or chlamydia., Results: A total of 1365 subjects were enrolled in the study across 10 sites. Adherence with mailing specimens obtained at home was excellent in both groups (84%-88%). The incidence of gonorrhea and/or chlamydia was 19.1 per 100 person-years (95% confidence interval, 15.1-22.1) for the treatment group and 18.5 per 100 person-years (15.1-22.8) for the observation arm, a difference that was not statistically significant., Conclusions: Young women were very amenable to home screening for BV, gonorrhea, and chlamydia. Treatment of asymptomatic BV with 1 week of oral metronidazole did not decrease the incidence of gonorrhea and/or chlamydia., Clinical Trials Registration: NCT00667368., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Bacterial vaginosis (BV) is a common polymicrobial disease associated with numerous negative reproductive health outcomes, including an increased risk of human immunodeficiency virus acquisition. BV is treatable with antibiotics, but relapse is common. A more detailed understanding of bacterial dynamics during antibiotic therapy for BV could identify conditions that favor establishment, maintenance, and eradication of BV-associated bacterial species, thereby improving treatment outcomes., Methods: We used mathematical models to analyze daily quantitative measurements of 11 key bacterial species during metronidazole treatment for 15 cases of BV., Results: We identified complete reorganization of vaginal bacterial composition within a day of initiating therapy. Although baseline bacterial levels predicted a longer time to clearance, all anaerobic species were eliminated rapidly within a median of 3 days. However, reemergence of BV-associated species was common following treatment cessation. Gardnerella vaginalis, a facultative anaerobe, was cleared more slowly than anaerobic BV-associated species, and levels of G. vaginalis often rebounded during treatment. We observed gradual Lactobacillus species growth, indicating that untargeted microbes fill the transient vacuum formed during treatment., Conclusions: Under antibiotic pressure, the human microbiome can undergo rapid shifts on a scale of hours. When treatment is stopped, BV-associated bacteria quickly reemerge, suggesting a possible role for intermittent prophylactic treatment., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Biofilms are microbial communities of surface-attached cells embedded in a self-produced extracellular matrix. They are of major medical significance because they decrease susceptibility to antimicrobial agents and enhance the spread of antimicrobial resistance. Biofilm-associated bacterial and fungal microorganisms have increasingly been recognized to play a role in multiple infectious diseases, particularly in their persistence and recurrence. More recently, biofilms have also been implicated in vaginal infections, notably bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), particularly in the setting of treatment failure and recurrence. The purpose of this review is to discuss the impact of biofilms on the management and treatment of BV and recurrent VVC and highlight the need for additional research and development of novel therapeutics targeting pathogenic vaginal biofilms., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study was designed to characterize the proteome of vaginal fluid (VF) from women with bacterial vaginosis (BV) in comparison with that from healthy women, and to evaluate the effect exerted by rifaximin vaginal tablets., Methods: Women with BV (n = 39) and matched healthy controls (n = 41) were included in the study. BV patients were distributed among four groups receiving different doses of rifaximin. Vaginal rinsings were collected at the screening visit from all the participants and at a follow-up visit from BV-affected women. The VF proteome was analysed by tandem mass spectrometry using an Orbitrap mass analyser., Results: A large number of human proteins were differentially expressed in women with BV in comparison with healthy women (n = 118) and in BV-affected women treated with rifaximin (n = 284). In both comparisons, a high proportion of the dysregulated proteins (∼20%) were involved in the innate immune response. Twenty-one of 24 proteins increased in abundance in women with BV versus healthy women and 31/59 proteins decreased after rifaximin treatment, suggesting a general reduction of the immune response resulting from the therapy. Major changes in protein abundance were found following treatment with 25 mg of rifaximin once daily for 5 days., Conclusions: BV is associated with a massive change in the VF proteome, mainly regarding the abundance of proteins involved in the innate immune response. Rifaximin at a dosage of 25 mg for 5 days modulated the vaginal proteome, counteracting the alterations associated with the BV condition.

Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate >10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.

Background: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection (STI) that is potentially associated with reproductive tract sequelae in women. This study aimed to estimate MG incidence and treatment failure and provide estimates of organism load in infection., Methods: 1110 women aged 16-25 years were recruited from primary care clinics in Australia. Women were tested for MG at baseline, 6 months, and 12 months, and MG organism load was measured by quantitative polymerase chain reaction (PCR). MG-positive cases were screened for MG 23S ribosomal RNA (rRNA) gene point mutations shown to confer azithromycin resistance using high-resolution melt following PCR., Results: MG incidence rate was 1.3 per 100 person-years (n=14; 95% confidence interval [CI], .8-2.3); women reporting 3 or more sex partners in the last 12 months had an increased rate of incident infection (rate ratio [RR], 5.1; 95% CI, 1.3-19.6]). There were 3 cases of MG reinfection (0.8 per 100 person-years [95% CI, .1-.9]. Organism load was higher for prevalent than incident infection (P=.04). There were 3 cases of treatment failure (9.4% [95% CI, 2.0-25.0]); organism load was higher in cases with treatment failure than in successfully treated cases (P<.01). An MG 23S rRNA mutation was detected in 5 cases (3 cases of treatment failure and 2 successfully treated)., Conclusions: Although MG incidence was relatively low, testing should be recommended for women considered to be at increased risk based on sexual history. Our results also suggest that organism load might be important in azithromycin treatment failure.

Background: Bacterial vaginosis (BV) recurrence posttreatment is common. Our aim was to determine if behaviors were associated with BV recurrence in women in a randomized controlled trial (RCT)., Methods: Symptomatic 18- to 50-year-old females with BV (≥3 Amsel criteria and Nugent score [NS] = 4-10) were enrolled in a 3-arm randomized double-blind RCT Melbourne Sexual Health Centre, Australia, in 2009-2010. All 450 participants received oral metronidazole (7 days) and were equally randomized to vaginal clindamycin, lactobacillus-vaginal probiotic or vaginal placebo. At 1, 2, 3, and 6 months, participants self-collected vaginal smears and completed questionnaires. Primary endpoint was NS = 7-10. Cox regression was used to estimate hazard ratios (HRs) for risk of BV recurrence associated with baseline and longitudinal characteristics., Results: Four hundred four (90%) women with postrandomization data contributed to analyses. Cumulative 6-month BV recurrence was 28% (95% confidence interval [CI], 24%-33%) and not associated with treatment. After stratifying for treatment and adjusting for age and sex frequency, recurrence was associated with having the same pre-/posttreatment sexual partner (adjusted HR [AHR] = 1.9; 95% CI, 1.2-3.0), inconsistent condom use (AHR = 1.9; 95% CI, 1.0-3.3), and being non-Australian (AHR = 1.5; 95% CI, 1.0-2.1), and halved with use of an estrogen-containing contraceptive (AHR = 0.5; 95% CI, .3-.8)., Conclusions: Risk of BV recurrence was increased with the same pre-/posttreatment sexual partner and inconsistent condom use, and halved with use of estrogen-containing contraceptives. Behavioral and contraceptive practices may modify the effectiveness of BV treatment., Clinical Trials Registration: ACTRN12607000350426.

Aims: To determine the mechanism of action of antimicrobial protein, lactosporin, against Gardnerella vaginalis and to evaluate its safety in vitro., Methods and Results: Bacillus coagulans ATCC 7050 was grown at 37°C for 18 h. The cell-free supernatant was concentrated 10-fold and screened for antimicrobial activity against indicator strain Micrococcus luteus. The mode of action of lactosporin was determined by measuring the potassium release and monitoring the changes in transmembrane potential (Δψ) and transmembrane pH (ΔpH) of the sensitive cells. Lactosporin caused the efflux of potassium ions from M. luteus cells and dissipation of ΔpH in G. vaginalis, while it had no effect on the Δψ. The safety of lactosporin was evaluated by using EpiVaginal(™) ectocervical (VEC-100) tissue model. Over 80% of the cells in the vaginal tissue remained viable after exposure to lactosporin for 24 h., Conclusions: Lactosporin potentially exerts its antimicrobial activity by selective dissipation of ΔpH and/or by causing leakage of ions from the sensitive cells. Safety studies suggest that lactosporin is a noncytotoxic antimicrobial for vaginal application., Significance and Impact of the Study: This study revealed that lactosporin is an effective and safe antimicrobial preparation with potential application for the control of bacterial vaginosis., (No claim to US Government works Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.)

Background: Bacterial vaginosis (BV) is the most common cause of vaginitis worldwide. Currently recommended treatments have poor efficacy and are associated with high rates of BV recurrence. We examined whether a longer duration of treatment with metronidazole or combination therapy with metronidazole and azithromycin would enhance the cure rates for BV. In addition, we examined factors other than drug therapy associated with cure., Methods: Women with symptomatic BV (defined by a modified Amsel criteria) were enrolled in a 4-arm study that compared metronidazole for 7 days versus 14 days, plus or minus azithromycin on days 1 and 3. Data regarding interim behaviors were also obtained, as were vaginal specimens for Gram staining., Results: At the first follow-up visit (7 days after the completion of therapy), there was a significant difference in cure rates among patients who received 7 days of metronidazole therapy, compared with those who received 14 days of therapy, combined across azithromycin therapy (P=.0003). There was no effect associated with azithromycin therapy. There were no differences in cure rates between any of the treatment groups at 21 days after completion of therapy. Abstinence or protected sex, refraining from douching, and a lower baseline Nugent score for the vaginal Gram stain were all significantly associated with cure., Conclusions: Cure rates for BV were significantly improved by 14 days of metronidazole treatment (compared with 7 days of treatment), but the effects were not sustained, suggesting that relapse or reinfection occurred. Combination therapy with the addition of azithromycin had no benefit. Lower baseline Nugent scores--presumably reflecting less complex vaginal flora--were significantly associated with cure, as was refraining from unprotected sex and from douching.

Background: We investigated associations between Atopobium vaginae and bacterial vaginosis (BV) and the role that A. vaginae plays in recurrent BV after oral metronidazole therapy., Methods: Women with abnormal vaginal discharge or odor were enrolled in a cross-sectional study (n=358); the proportion of those infected with Gardnerella vaginalis and A. vaginae was determined by polymerase chain reaction. Women with BV (Nugent score [NS] 7-10 or 4-6 with > or =3 Amsel criteria; n=139) were treated with oral metronidazole (400 mg twice a day for 7 days) and examined at 1, 3, 6, and 12 months or until they reached an NS of 7-10 and recurrence of A. vaginae and G. vaginalis infection was established., Results: A. vaginae and G. vaginalis were highly sensitive for BV--96% (95% confidence interval [CI], 91%-98%) and 99% (95% CI, 97%-100%), respectively. However, A. vaginalis was more specific for BV (77% [95% CI, 71%-82%]) than was G. vaginalis (35% [95% CI, 29%-42%]). G. vaginalis was detected in 100% and A. vaginae in 75% of women with recurrent BV; higher organism loads were present in women with recurrent BV. A. vaginae was rarely detected without G. vaginalis, and women in whom both organisms were detected had higher rates of recurrent BV (83%) than women infected with G. vaginalis only (38%) (P<.001)., Conclusions: Infection with A. vaginae is more specific for BV than infection with G. vaginalis. The higher recurrence rates in women in whom both A. vaginae and G. vaginalis were detected suggest that A. vaginae makes a significant contribution to BV. However, its etiological role remains unclear.

Background: We wished to determine recurrences of bacterial vaginosis (BV) after treatment over the course of 12 months and to establish factors associated with recurrence., Methods: Women with symptomatic BV (a Nugent score [NS] of 7-10 or of 4-6 with >or=3 Amsel criteria) were enrolled. BV was treated with 400 mg of oral metronidazole twice a day for 7 days. Participants completed a questionnaire and vaginal swabs were collected at 1, 3, 6, and 12 months; the study end point was an NS of 7-10., Results: A total of 121 (87%) women with an NS of 7-10 and 18 (13%) with an NS of 4-6 and >or=3 Amsel criteria were enrolled; 130 (94%) returned >or=1 vaginal samples. Sixty-eight women (58% [95% confidence interval {CI}, 49%-66%]) had a recurrence of BV (NS 7-10), and 84 (69% [95% CI, 61%-77%]) had a recurrence of abnormal vaginal flora (NS 4-10) by 12 months. A past history of BV, a regular sex partner throughout the study, and female sex partners were significantly associated with recurrence of BV and abnormal vaginal flora by multivariate analysis; the use of hormonal contraception had a negative association with recurrence., Conclusion: Current recommended treatment is not preventing the recurrence of BV or abnormal vaginal flora in the majority of women; factors associated with recurrence support a possible role for sexual transmission in the pathogenesis of recurrent BV.

Background: Chlamydia trachomatis and/or Neisseria gonorrhoeae account for approximately one-third to one-half of pelvic inflammatory disease (PID) cases. Thus, up to 70% of cases have an unknown, nongonococcal/nonchlamydial microbial etiology., Methods: We investigated the associations of N. gonorrhoeae, C. trachomatis, bacterial vaginosis, anaerobic bacteria, facultative bacteria, and lactobacilli with endometritis among 278 women with complete endometrial histology and culture from the PID Evaluation and Clinical Health Study., Results: Women with acute endometritis were less likely to have H(2)O(2)-producing Lactobacillus species (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01-0.8) and more likely to be infected with C. trachomatis (OR, 16.2; 95% CI, 4.6-56.6), N. gonorrhoeae (OR, 11.6; 95% CI, 4.5-29.9), diphtheroids (OR, 5.0; 95% CI, 2.1-12.2), black-pigmented gram-negative rods (OR, 3.1; 95% CI, 1.4-7.0), and anaerobic gram-positive cocci (OR, 2.1; 95% CI, 1.0-4.3) and to have bacterial vaginosis (OR, 2.4; 95% CI, 1.3-4.3)., Conclusions: We conclude that bacterial vaginosis-associated organisms are frequent among women with PID. Because these organisms were strongly associated with endometritis, we recommend that all women with PID be treated with regimens that include metronidazole.

Accumulating evidence has associated bacterial vaginosis (BV) with serious medical complications such as premature delivery. The present article synthesizes available data on the treatment of nonpregnant and pregnant women with BV to prevent preterm delivery. A literature search identified articles published since 1976 that evaluated treatment of BV. An intention-to-treat sensitivity analysis was performed, to better compare studies. Studies that evaluated therapy efficacy varied with regard to diagnostic criteria, patient characteristics, clinicians, and laboratories. Therapies varied in efficacy for cure 4 or more weeks after therapy, from 48% to 85%. Intervention studies to reduce BV-related adverse outcomes of pregnancy differed in populations studied, medication used, type of therapy (oral or intravaginal), and timing of treatment. The benefit of treating women at high risk with oral metronidazole has been shown in several studies; however, the effect of treating women without a history of premature delivery is unclear. The use of intravaginal clindamycin therapy, especially during the latter half of the second trimester and thereafter, appears to increase infections during the neonatal period.

To assess the effect of treatment of vaginal infections on vaginal shedding of cell-free human immunodeficiency virus type 1 (HIV-1) and HIV-1-infected cells, HIV-1-seropositive women were examined before and after treatment of Candida vulvovaginitis, Trichomonas vaginitis, and bacterial vaginosis. For Candida (n=98), vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10) copies/swab (P<.001), as did the prevalence of HIV-1 DNA (36% to 17%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.5). For Trichomonas vaginitis (n=55), HIV-1 RNA decreased from 3.67 to 3.05 log(10) copies/swab (P<.001), but the prevalence of HIV-1 DNA remained unchanged (22%-25%; OR, 0.8; 95% CI, 0.3-2.2). For bacterial vaginosis (n=73), neither the shedding of HIV-1 RNA (from 3.11 to 2.90 log(10) copies/swab; P=.14) nor the prevalence of DNA (from 21% to 23%; OR, 0.8; 95% CI, 0.3-2.0) changed. Vaginal HIV-1 decreased 3.2- and 4.2-fold after treating Candida and Trichomonas, respectively. These data suggest that HIV-1 transmission intervention strategies that incorporate diagnosis and treatment of these prevalent infections warrant evaluation.

There is growing evidence that the pathogenic effects of bacterial vaginosis may not be confined to the lower genital tract. Possible associations with infertility and effects on fertilization and implantation were studied in patients undergoing in-vitro fertilization (IVF) treatment. High vaginal swabs taken at the time of oocyte collection were assessed by Gram staining. The prevalence of bacterial vaginosis and of intermediate and normal flora in 301 patients was 25.6, 14.0 and 60.4% respectively. Bacterial vaginosis was more prevalent in patients with tubal (31.5%, n = 149) compared with non-tubal (19.7%, n = 152) infertility (odds ratio (OR) 1.87, CI 1.11-3.18, P = 0.02). Bacterial vaginosis did not have an adverse effect on fertilization rate. Further, no significant difference in implantation rates was seen when comparing bacterial vaginosis (15. 8%, OR 1.03, CI 0.66-1.61) and intermediate flora (13.1%, OR 0.82, CI 0.45-1.52) with normal flora (15.5%). Though confidence intervals around the observations were relatively wide, the findings suggest that routine screening for bacterial vaginosis in the hope of improving the success of IVF treatment is not justified. The prevention of complications in pregnancy associated with bacterial vaginosis might be a more relevant indication for screening at the time of IVF treatment, in particular patients with tubal disease, if treatment were shown to be effective for that particular purpose. However, antibiotic treatment before IVF has been shown to be positively disadvantageous for IVF by encouraging other organisms.

We reviewed data on the treatment of bacterial vaginosis published from 1993 through 1996. For nonpregnant women, we recommend use of metronidazole (500 mg orally twice daily for 7 days), clindamycin vaginal cream (2%, once daily for 7 days), or metronidazole vaginal gel (0.75%, twice daily for 5 days) as the preferred treatment for bacterial vaginosis. For pregnant high-risk women (women with a prior preterm birth), the objective of the treatment is to prevent adverse outcomes of pregnancy, in addition to relief of symptoms. Thus, systemic therapy for possible subclinical upper tract infection as well as medication that has been studied in pregnant women are preferable. Therefore, we recommend metronidazole (250 mg orally three times a day for 7 days). For pregnant low-risk women (women without a prior preterm birth) with symptomatic disease, the main objective of the treatment is to relieve symptoms. We recommend metronidazole (250 mg orally three times a day for 7 days). Data do not support routine treatment of male sex partners.

Several in vitro studies have shown nonoxynol-9 (N-9) to be toxic to lactobacilli, especially to strains that produce H2O2. Data from a randomized, double-blind, placebo-controlled crossover trial that investigated the safety and toxicity of 2 weeks of daily vaginal application of an N-9 gel were analyzed, to examine the effect of N-9 use on vaginal lactobacilli and bacterial vaginosis. In vivo, N-9 promoted sustained colonization by H2O2-producing lactobacilli among women already colonized (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2-2.7). In addition, use of N-9 for 2 weeks reduced the likelihood of bacterial vaginosis (RR, 0.5; 95% CI, 0.3-1.0). In contrast, N-9 use by women initially colonized only by non-H2O2-producing lactobacilli resulted in loss of vaginal lactobacilli (RR, 2.5; 95% CI, 1.2-5.3). These data suggest that daily use of N-9 does not adversely affect vaginal colonization by H2O2-producing lactobacilli but that such use may promote loss of non-H2O2-producing strains.

The in vitro activity of DU-6859a, a new fluoroquinolone, was compared with those of other fluoroquinolones against clinical isolates of anaerobic bacteria and Gardnerella vaginalis. DU-6859a was the most active agent; it inhibited 90% of isolates of almost all species tested, including Bacteroides fragilis at < or = 0.39 micrograms/mL. Although the other quinolones tested were active against gram-positive anaerobes, inhibiting their growth at < or = 1.56 micrograms/mL, these agents were less active against the B. fragilis group and Prevotella bivia (90% of which were inhibited at > or = 6.25 micrograms/mL). Mobiluncus species and G. vaginalis, which are well associated with bacterial vaginosis, were inhibited by DU-6859a at 0.1 microgram/mL. These results suggest that DU-6859a is a promising oral agent for the treatment of bacterial infections due to anaerobic bacteria; however, further studies, including determination of vaginal levels of this compound, should be performed to study the role of DU-6859a in the treatment of bacterial vaginosis.

Purpuromycin and its semi-synthetic derivative MDL 63,604 had in-vitro activity similar to that of amphotericin B against isolates of Candida albicans. MDL 63,604 had activity similar to that of metronidazole against Trichomonas vaginalis. Both compounds were very active against most species of Gram-positive and Gram-negative anaerobes and against Gardnerella vaginalis. MDL 63,604 had significantly lower MICs than purpuromycin against T. vaginalis and most of the bacteria, probably due to antagonism of purpuromycin's activity by medium supplements (blood or serum). Purpuromycin or related compounds may have a potential role in the topical treatment of vaginitis and vaginosis.

The minimum inhibitory concentrations (MIC) of clindamycin for 62 consecutive isolates of Neisseria gonorrhoeae were found to be 0.03-4 mg/L; the MIC50 and MIC90 were 0.125 and 2.0 mg/L respectively. Seven women treated with clindamycin vaginal cream had cervical mucus samples taken after seven days treatment. The concentrations of clindamycin achieved in the cervical mucus were 30-150 times higher (141-337 mg/L) than the highest MIC of the 62 N. gonorrhoeae isolates. Clindamycin vaginal cream is being used increasingly in Genitourinary Medicine clinics and General Practice for the treatment of bacterial vaginosis. This study shows that clindamycin vaginal cream achieves intra cervical concentrations that are high enough to inhibit N. gonorrhoeae. Empirical use of this therapy should be preceded by urethral and cervical swabs for N. gonorrhoeae in any woman at risk of gonorrhoeae.

In recent clinical studies, clindamycin phosphate cream administered intravaginally has been shown to be efficacious in the treatment of bacterial vaginosis (BV). In support of the safety profile for this dosage form, a study assessing the systemic absorption of clindamycin was undertaken in five BV patients and six healthy volunteers who were dosed with 5 mL (100 mg) clindamycin phosphate 2% cream intravaginally once daily in the evening for 7 days. Two weeks later, a single 100 mg dose of clindamycin phosphate sterile solution was administered as a 4 min iv infusion. Serial blood samples were collected on days 1, 4, and 7 after dosing with the cream and over a 16 h period after the iv treatment. Clindamycin concentrations in serum samples were assayed by capillary gas chromatography. After treatment with the cream, steady-state serum clindamycin concentrations were reached by 24 h in all but one subject in each group. Mean absolute bioavailability was 2.7%-4.3% in the BV group and 2.7%-4.7% in the healthy group. These results indicate that systemic exposure to clindamycin from intravaginal administration of clindamycin phosphate cream is minimal.