Observational prospective study on Lactobacillus plantarum P 17630 in the prevention of vaginal infections, during and after systemic antibiotic therapy or in women with recurrent vaginal or genitourinary infections.

We performed a prospective cohort parallel observational study on the use of Lactobacillus plantarum P 17630 in the prevention of vaginal infections. Eligible were women with a diagnosis of bacterial vaginosis (<15 days) and documented history of recurrent vaginal infections; and/or cystitis (<15 days); and/or treatment with antibiotics for bacterial respiratory tract infections during the week before the study entry. Study subjects were prescribed Lactobacillus plantarum P 17630 > 100.000.000 UFC one vaginal capsule per day for 6 days, then a capsule per week for 16 weeks. Eligible subjects were enrolled in two parallel cohorts: 85 women using (group A) and 39 not using (group B) Lactobacillus plantarum P 17630. The risk of recurrent infection within 4 months from the study entry, was higher among untreated women: multivariate OR 2.6 (95%CI 0.7-9.4). The modification of presence/intensity or symptoms was significant in both the study groups (p < .001). Impact statement What is already known on this subject? The Lactobacillus plantarum P 17630 has been shown to be active in the treatment of bacterial vaginosis and vaginal candidiasis. No data are available on its efficacy in the prevention of recurrent vaginal or urological infection or as a prevention strategy during systemic treatment with antibiotics. What do the results of this study add? This observational study suggests that Lactobacillus plantarum given for 4 months may lower the risk of recurrent infection in women with recurrent vaginal or genitourinary infection or after antibiotic systemic treatment for bacterial respiratory tract infection. The finding, however, is not statistically significant, possibly due to the lower than expected rate of infection observed in our population and consequently the limited power of the study. What are the implications of these findings for clinical practice and/or further research? New studies are needed in order to evaluate in different populations the role of Lactobacillus plantarum in lowering the risk of recurrent infection in a high-risk populations.

Evaluation of safety margins of Chenopodium album seed decoction: 14-day subacute toxicity and microbicidal activity studies.

BACKGROUND: Sperm immobilizing activity and plausible mechanism of action of Chenopodium album seed decoction (CAD) have been elucidated in our earlier studies. The present study has been carried out to explore the safety standards of CAD along with microbicidal properties as prerequisite for its use as a topically applicable vaginal contraceptive. METHODS: The safety standards of CAD were assessed by a) Hemolytic index determination using rabbit erythrocytes, to set the doses of the other experiments, b) Dermal irritancy test using refined version of Draize scoring system on rabbits, c) Possible effect on local tissues and reproductive performance in female rats after fourteen daily single dose application, d) PCNA staining- to evaluate the effect of CAD on vaginal tissue proliferation, e) TUNEL assay- to examine its ability to induce in situ apoptosis in the vaginal tissue sections of the treated animals, and f) Microbicidal activity- to explore the effect of CAD on the growth of Lactobacillus acidophilus and Candida albicans. RESULTS: In vitro irritation studies on rabbit erythrocytes revealed the hemolytic index of CAD to be 8.2 mg/ml. The dermal irritation test showed it to be a non-irritant even at higher doses. Intra vaginal application of CAD in rat vagina for 14 consecutive days caused slight reversible inflammation on vaginal epithelial cells at doses as high as 82 mg/ml. However, at this dose level it neither had any adverse effect on vaginal tissue proliferation nor did it cause in situ apoptosis as evident from PCNA staining and TUNEL assay. Fertility and fecundity were restored 4-15 days after withdrawal of CAD application. At dose level 10 times that of its spermicidal MEC (minimum effective concentration), CAD did not block the growth of Lactobacillus, although the size of individual colony was marginally reduced. However, growth of the pathogenic fungus Candida albicans was completely inhibited with 20 mg/ml of CAD. CONCLUSION: The overall result evolved from the study strengthens the candidature of CAD as a safe microbicidal spermicide. It is almost non-irritant to rabbit skin and rat vaginal tissues at doses 10 fold higher than its hemolytic index. The effect of CAD on Lactobacillus culture was not highly encouraging but it prevented the growth of the fungal pathogen Candida albicans at 20 mg/ml of CAD.

Qualification of a non-animal vaginal irritation method admitted as nonclinical assessment model (NAM) in the Incubator Phase of the United States Food and Drug Administration (US FDA) Medical Devices Development Tool (MDDT).

The U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) classifies personal lubricants as Class II medical devices. Because of this status and the nature of body contact common to personal lubricants, CDRH reviewers routinely recommend a standard biocompatibility testing battery that includes: an in vivo rabbit vaginal irritation (RVI) test; an in vivo skin sensitization test, such as the guinea pig maximization test (GPMT); and an in vivo acute systemic toxicity test using mice or rabbits. These tests are conducted using live animals, despite the availability of in vitro and other non-animal test methods that may be suitable replacements. The only test included in the biocompatibility battery currently conducted using in vitro assay(s) is cytotoxicity. FDA's recently launched Predictive Toxicology Roadmap calls for the optimization of non-animal methods for the safety evaluation of drugs, consumer products and medical devices. In line with these goals, a Consortium comprising the Institute for In Vitro Sciences, Inc. (IIVS), industry, the Consumer Healthcare Products Association (CHPA), and the PETA International Science Consortium (PETA-ISC) is qualifying the use of an in vitro testing method as replacement for the RVI test. Participating companies include manufacturers of personal lubricants and those interested in the advancement of non-animal approaches working collaboratively with the FDA CDRH to develop an in vitro testing approach that could be used in place of the RVI in pre-market submissions. Personal lubricants and vaginal moisturizers with diverse chemical and physical properties (e.g., formulation, viscosity, pH, and osmolality) in their final undiluted form will be the focus of the program. In vitro vaginal irritation data generated using commercially available human reconstructed vaginal tissue model(s) will be paired with existing in vivo RVI data and analyzed to develop a Prediction Model for the safety assessment of these products. This research plan has been accepted into the FDA CDRH Medical Device Development Tools (MDDT) program as a potential non-clinical assessment model (NAM). The proposed NAM aligns with the goals of the recently launched FDA Roadmap to integrate predictive toxicology methods into safety and risk assessment with the potential to replace or reduce the use of animal testing.

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.

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

BACKGROUND: The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit. OBJECTIVE: To see if a higher dose of amoxicillin will lead to more rapid improvement. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines. INTERVENTIONS: Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR). MAIN MEASURE: The primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment. KEY RESULTS: Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048). CONCLUSIONS: Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02340000.

Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis.

Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10-12 (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10-12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.

Vulvar fixed drug eruption. A report of 13 cases.

BACKGROUND: The fixed drug eruption (FDE) is an uncommon adverse event related to drug ingestion that presents with a recurrent eruption occurring on the same site with each drug exposure. The genital area is a well-recognized site for the so-called nonpigmenting fixed drug eruption. Most of the medical literature has focused on the male genitalia. In the female, FDE may present as acute, recurrent or chronic vulvitis that resolves rapidly when the offending drug is ceased. CASES: Thirteen women aged 15-84 were seen with vulvitis related to drug ingestion. Four of those patients experienced 1 acute episode related to diverse medications. Two presented with acute recurrent vulvitis related to ingestion of ibuprofen. Seven women, aged 58-77, presented with chronic erosive vulvitis, nonspecific on biopsy and unresponsive to all therapeutic measures other than the cessation of the offending drug, most often HMG Co-A or COX-2 inhibitors. CONCLUSION: In younger women, FDE may present as recurrent acute vulvitis often related to analgesic ingestion. In older patients, FDE presents as a perplexing, unresponsive erosive vulvitis. Genital FDE is characteristically nonpigmenting, erosive, bilaterally symmetric and nonspecific on biopsy. A drug history is imperative in any patient with chronic unresponsive vulvitis.

[Anti-infectious defense of vagina during use of low-dose monophasic contraceptives].

Increase in incidence of candidal colpitis has been observed during use of contraceptive drugs. Elimination of staphylococci from genital tract after use of contraceptives was detected in 34,7% of patients. Composition of other aerobic microflora did not change. Nonspecific immune reaction was characterized by intensified phagocytosis, increase of results of NBT reduction test and level of proinflammatory cytokines. Conclusion about inappropriateness of using low-dose oral contraceptives in patients with recurrent vulvovaginal candidosis was made. Such contraceptives can be recommended to women with prolonged inflammatory diseases of reproductive system.

Impact of a progesterone-releasing intravaginal device and inflammatory reaction on ovarian activity in embryo-recipient anestrus mares.

This study aimed to correlate the inflammatory reaction (IR) caused by a progesterone-releasing intravaginal device (P4) with ovarian activity and pregnancy rate (PR) in embryo-recipient anestrus mares (to decrease the spring transitional period). 50 animals were assigned to three groups: GP4 (P4 group; n = 16), GP4OH (P4 + oxytetracycline hydrochloride and hydrocortisone sprayed onto the device; n = 14), and GNP4 (no intravaginal P4; n = 20). The administration protocol for GP4 was: Day 0, 750 mg P4 + ovarian examination by ultrasonography (US) + vaginal sample collection; Day 8, US; Day 11, P4 removal + 7.5 mg PGF2α + US + second vaginal sample collection; Days 13 to 16, US; Days 17 to 21, US + 750 IU hCG to mares with follicles 35 mm or more in diameter; Days 19 to 23 US (ovulation check); Days 24 to 28, embryo transfer + intravenous flunixin meglumine; and Days 30, US pregnancy diagnosis. The GP4OH and GNP4 mares received the same administration protocol as GP4, except that no P4 device was administered to the GNP4 group on Day 0. Although neutrophil-mediated IR occurred in the GP4 and GP4OH groups, the IR was significantly reduced in GP4OH as compared with that in GP4 (P < 0.0001). From Day 0 to Day 17, the GP4 and GP4OH mares developed a greater number of follicles per animal than did the GNP4 mares (P < 0.05), and the average diameter of the follicles was larger in the GP4 and GP4OH mares. The ovulation rates in GP4, GP4OH, and GNP4 mares were, respectively, 43.7%, 64.3%, and 30.0%, and ovulation occurred at 6.8, 6.5, and 23 days after P4 removal (P < 0.05). On Day 17, endometrial edema was verified in 50%, 64.2%, and 35.0% of the GP4, GP4OH, and GNP4 mares, and the PRs after embryo transfer were 80%, 100%, and 66.6%, respectively. Although intravaginal devices caused IR in both the device-recipient groups (P = 0.0001), IR and vaginitis had no negative impact on follicle diameter, ovulation rate, period to ovulation after the removal of P4, endometrial edema, or PR. In addition, P4 reactivated the ovarian function and the IR eliminated a large percentage of bacteria (Bacillus spp., Enterobacter spp., Proteus spp., Pseudomonas spp., and Staphylococcus spp.), especially in GP4; the application of oxytetracycline hydrochloride and hydrocortisone on the devices reduced the severity of vaginitis.

Evaluation of immunological markers of ovine vaginal irritation: Implications for preclinical assessment of non-vaccine HIV preventive agents.

The presence of genital inflammatory responses and a compromised vaginal epithelial barrier have been linked to an increased risk of HIV acquisition. It is important to assure that application of candidate microbicides designed to limit HIV transmission will not cause these adverse events. We previously developed high resolution in vivo imaging methodologies in sheep to assess epithelial integrity following vaginal application of a model microbicide, however characterization of genital inflammation in sheep has not been previously possible. In this study, we significantly advanced the sheep model by developing approaches to detect and quantify inflammatory responses resulting from application of a nonoxynol-9-containing gel known to elicit vaginal irritation. Vaginal application of this model microbicide resulted in foci of disrupted epithelium detectable by confocal endomicroscopy. Leukocytes also infiltrated the treated mucosa and the number and composition of leukocytes obtained by cervicovaginal lavage (CVL) were determined by differential staining and flow cytometry. By 18h post-treatment, a population comprised predominantly of granulocytes and monocytes infiltrated the vagina and persisted through 44h post-treatment. The concentration of proinflammatory cytokines and chemokines in CVL was determined by quantitative ELISA. Concentrations of IL-8 and IL-1ß were consistently significantly increased after microbicide application suggesting these cytokines are useful biomarkers for epithelial injury in the sheep model. Together, the results of these immunological assessments mirror those obtained in previous animal models and human trials with the same compound and greatly extend the utility of the sheep vaginal model in assessing the vaginal barrier and immune microenvironment.

A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia.

A phase I trial was conducted of the vitamin A derivative beta-all-trans-retinoic acid (vitamin A acid; TRA), delivered via a collagen sponge and cervical cap for mild or moderate intraepithelial cervical neoplasia. On the basis of known skin and mucosal membrane toxicity, a concentration of 0.05% TRA in a cream-based vehicle was selected as the starting dose and was escalated later with the use of a modified Fibonacchi scale. The delivery device and the TRA were changed daily for 4 days, and side effects were assessed on days 1, 2, 3, 4, 8, and 30 by clinical and colposcopic examination. Vaginal, cervical, and systemic toxicity were evaluated in 35 patients. No dose-related systemic effects were found; mild cervical inflammation increased in many patients at higher doses. Unacceptably high vaginal toxicity was reached at a TRA concentration of 0.484%. A concentration of 0.372% TRA is recommended for use in phase II trials in mild and moderate cervical intraepithelial neoplasia.

Safety and tolerability of chlorhexidine gluconate (2%) as a vaginal operative preparation in patients undergoing gynecologic surgery.

BACKGROUND: The use of chlorhexidine gluconate (CHG) as an intraoperative vaginal preparation has been shown to be more effective than vaginal povidone-iodine (PI) in decreasing vaginal bacterial colony counts. However, PI remains the standard vaginal preparation because of concerns of CHG's potential for vaginal irritation. The primary outcome of this study is a comparison of the rate of patient-reported vaginal irritation between 2% CHG and PI. METHODS: Consecutive patients were enrolled in a pre-post study. Group 1 consisted of consecutive patients who received PI as a vaginal preparation. Group 2 consisted of consecutive patients who received 2% CHG as a vaginal preparation. Patients used a standardized instrument to report irritation to trained nurse practitioners 1 day after surgery. RESULTS: A total of 117 patients received vaginal operative preparation during the course of the study, with 64 patients in group 1 and 53 patients in group 2. Of the patients in group 1, 60 (93.7%) reported no vaginal irritation, 3 (4.69%) reported mild irritation, and 1 (1.56%) reported moderate irritation. In group 2 (2% CHG vaginal preparation), all of the patients (100%) reported no vaginal irritation (P = .38). CONCLUSIONS: The use of 2% CHG as a vaginal operative preparation is not associated with increased vaginal irritation compared with PI in gynecologic surgery. It can safely be used, taking advantage of its efficacy in reducing vaginal bacterial colony counts.

Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur &61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.

Abuse of antibiotics. A study of patients attending a university clinic.

Self-treatment with antibiotics was evaluated among patients at a university health service in an 18-month period. Sixty-two students ingested antibiotics, usually tetracycline (40%) or penicillin (21%), for varying intervals before seeking medical care. Respiratory symptoms were the most common reason (40%). The most frequent drug source was residual medication obtained by prescription from a private physician for a prior illness (43%). Although self-therapy was of short duration, the negative bacteriologic cultures obtained on our evaluation in all but four patients challenged precise diagnosis. The findings indicate that inappropriate use of antibiotics by patients would be curtailed by prescribing only the exact amount needed for a given illness and by emphasizing the need for completion of the course of therapy.

Anti-Human Immunodeficiency Virus Activity of Thiol-Ene Carbosilane Dendrimers and Their Potential Development as a Topical Microbicide.

The concept of a "microbicide" was born out of the lack of a vaccine against HIV and the difficulty of women in ensuring the use of preventive prophylaxis by their partners, especially in developing countries. Approaches using polyanionic carbosilane dendrimers have shown promise in the development of new microbicides. We have developed and evaluated two anionic carbosilane dendrimers with sulfonate and carboxylate terminal groups, G2-STE16 and G2-CTE16. Both dendrimers showed high biosafety in human epithelial cell lines derived from the vagina and in primary blood human cells (PBMCs). The dendrimers not only have a greater capacity to block the entry of different X4- and R5-HIV-1 isolates into epithelial cells but also prevent the HIV-1 infection of activated PBMCs. The treatment of epithelial cells with different carbosilane dendrimers did not produce changes in the activation or proliferation of PBMCs or in the expression of CD4, CCR5 or CXCR4. Computational modeling showed significantly higher affinities for the complexes G2-STE16/gp120 and G2-CTE16/gp120. Moreover, no irritation or vaginal lesions were detected in female BALB/c mice after vaginal administration of the dendrimers. Summing up, G2-STE16 and G2-CTE16 are easy to synthesize and compatible with functional groups, and the purification steps are easy and short. Our results have clearly demonstrated that these dendrimers have high potency as a topical microbicide against HIV-1 infection.

A comparative clinical trial of the contraceptive sponge and Neo Sampoon tablets.

Neo Sampoon, a foaming vaginal tablet containing 60 mg of the spermicide menfegol, and the Collatex sponge (now marketed in the United States as the Today sponge), a dome-shaped polyurethane device that contains 1 g of nonoxynol-9, were compared in terms of effectiveness, safety, and acceptability. Both methods were new to the Maribor General Hospital, Yugoslavia, where the trial was conducted among 450 volunteers randomly assigned to one of the two methods. At 12 months, the life-table pregnancy rate per 100 women for the Neo Sampoon group was 12.8, compared with a rate of 10.4 among the sponge users (P greater than .10). After pregnancy, the second most frequent reason for termination was discomfort, with a 12-month termination rate due to this cause of 6.9 per 100 women in the Neo Sampoon group and 6.2 in the sponge group. Although fewer than a quarter of the volunteers had any experience with barrier methods before this trial, the life-table continuation rate was high in both groups, with more than 70% using their assigned method for the full 12 months. Also, upon conclusion of the study, 41% of the volunteers chose another barrier contraceptive method. Although the effectiveness of the sponge and Neo Sampoon is not comparable to that of the pill or IUD, both vaginal methods appear to be safe and acceptable additions to the range of contraceptive choices.

Effects of the spermicide nonoxynol-9 on the pregnant uterus and the conceptus of rat.

In a series of experiments the embryotoxic potential of nonoxynol-9 (N-9) was investigated in adult female rats given a single per vaginam application of 5 mg/100 g (0.1 ml/100 g) of this spermicide on day 3 (pre-implantation period) or 7 (postimplantation period) of gestation. Control rats were given physiologic saline (0.1 ml/100 g) intravaginally. The vulvar labia were apposed for 24 h by metallic clips to prevent leakage of the solution. Groups of dams treated on pregnancy days 3 and 7 were killed by CO2 inhalation on gestational days 6, 9, 12 and 15, and 8, 9, 10, 12 and 15, resorption and total resorption of the conceptus, embryonal and placental resorption and total resorption of the conceptus, embryonal and placental necrosis, placentitis, endometritis, multicystic endometrium, and diffuse or segmental dilatation of the uterine horns. Generally, the incidence of these lesions varied with the length of time after N-9 was administered and it was consistently higher in the females treated on pregnancy day 3 than in those treated on day 7. Acute vaginitis waned with time after the application of N-9. It was concluded that under the conditions of this study, N-9 is embryocidal/fetocidal in the rat if administered during the first week of gestation. The impairment of embryonal/fetal development was attributed to the N-9-induced changes in the endometrium, the placenta and/or the embryo.

Morphologic evidence for vaginal toxicity of Delfen contraceptive cream in the rat.

The morphologic effects of Delfen contraceptive cream on the female genital tract were evaluated in young female rats given a single per vaginum application (0.1 g/100 g) of this spermicidal agent. Control rats received intravaginal instillates of 0.1 ml/100 g of physiological saline. Immediately after dosing, the vulvas of one-half of the treated and control females were shut by metallic clips to prevent leakage of the material. The females were killed 24 h post-treatment. The genital tracts of all control females were unremarkable. Treated females, with or without vulvar labial apposition, developed acute cervico-vaginitis of varied intensity, but as many as half of those without labial apposition failed to develop any pathologic changes. It was concluded that Delfen cream is capable of causing genital tract injury in rats similar to that induced by an aqueous solution of the active ingredient, nonoxynol-9, and that the incidence of this effect is enhanced if leakage of the cream is prevented by application of vulvar clips.

A randomized Phase I vaginal safety study of three concentrations of C31G vs. Extra Strength Gynol II.

BACKGROUND: C31G is an antimicrobial and spermicidal agent that contains two surface-active compounds, cetyl betaine and myristamine oxide. It is being developed as a vaginal microbicide and contraceptive. METHOD: Three C31G concentrations (0.5%, 1.0% and 1.7%) were tested and compared with Extra Strength Gynol II(R), a marketed spermicide containing 3% nonoxynol-9 (N-9), in a randomized, double-blinded, Phase I, dose-escalation study to assess genital irritation (by subject report, visual examination at pelvic examination and colposcopy), plasma and vaginal lavage levels of C31G, product leakage, systemic safety and acceptability. Women were randomized to use 3.5 mL of one of the three C31G products or the N-9 gel at night for 7 days then twice daily for another 7 days. Pelvic and colposcopic evaluations were performed after 7 and 14 days of product use. RESULTS: The percent of women experiencing irritation in the 0.5% and 1.0% C31G groups in the study were similar to each other and were lower than the percent experiencing irritation in the 1.7% and N-9 groups, which were also similar to each other. Differences were statistically significant between 1.0% C31G vs. N-9 at 7 days and between 0.5% C31G and 1.0% C31G vs. N-9 at 14 days. There was no significant difference between groups in leakage or acceptability. No C31G was detected in the plasma of any volunteer. CONCLUSIONS: These results suggest that 0.5% and 1.0% C31G are less irritating to the female genital tract than 1.7% C31G or Extra Strength Gynol II.