The anti-HIV microbicide candidate RC-101 inhibits pathogenic vaginal bacteria without harming endogenous flora or mucosa.

PROBLEM: Vaginal microbicides represent a promising approach for preventing heterosexual HIV transmission. However, preclinical evaluation should be conducted to ensure that microbicides will be safe for human cells and healthy microflora of the female reproductive tract. One microbicide candidate, RC-101, has been effective and well tolerated in preliminary cell culture and macaque models. However, the effect of RC-101 on primary vaginal tissues and resident vaginal microflora requires further evaluation. METHOD OF STUDY: We treated primary vaginal tissues and vaginal bacteria, both pathogenic and commensal, with RC-101 to investigate effects of this microbicide. RESULTS: RC-101 was well tolerated by host tissues, and also by commensal vaginal bacteria. Simultaneously, pathogenic vaginal bacteria, which are known to increase susceptibility to HIV acquisition, were inhibited by RC-101. CONCLUSIONS: By establishing vaginal microflora, the specific antibacterial activity of RC-101 may provide a dual mechanism of HIV protection. These findings support advancement of RC-101 to clinical trials.

[Evaluation of efficacy of ketoconazole 800 mg-clindamycin 100 mg tablets vaginal against ketoconazole 800 mg- clindamycin 100 mg vaginal capsules in candida vaginitis and vaginosis]. / Evaluación de la eficacia de ketoconazol 800 mg-clindamicina 100 mg tabletas vaginales, contra ketoconazol 800 mg-100 mg de clindamicina cápsulas vaginales en vaginitis candidiásica y vaginosis.

BACKGROUND: pharmaceutical forms (presentations) influence treatment compliance and therefore the effectiveness. Here we present the results in the relief of vaginitis and vaginosis with two different dosage forms. OBJECTIVE: To compare the efficacy and safety of a combination of ketoconazole 800 mg + clindamycin in soft vaginal gel capsules 100 mg (vaginal capsules) against ketoconazole 800 mg + 100 mg clindamycin vaginal tablets (TV) in the management of vaginitis by C. albicans and/or vaginosis. MATERIAL AND METHOD: In a randomized, multicenter, comparative open label study, patients between 18 and 60 years with a diagnosis of vaginitis by C. albicans and/or vaginosis were included. Patients were evaluated clinically and direct exam of genital discharge and culture were performed. Patients were randomized to one of two treatments vaginal tablets or vaginal capsules, for 3 days. RESULTS: one hundred an sitxty nine patients were included, 85 in TV Group and 84 in vaginal capsules group. We found significant statistical difference in clinical response for tablet group at day three for burning p = 0.032 and itching p = 0.043. Microbiological cure was observed in patients with vaginitis by C. albicans, 92.5% in Group TV vs. 90.47% vaginal capsules group, all patients with G. vaginalis at baseline were negative for the organism at the end of the study, cure in patients with mixed infections were 78.94% for TV group vs. 78.26% vaginal capsules; group no adverse events were reported during treatment. CONCLUSIONS: Treatment of vaginitis/vaginosis with vaginal tablets is clinically better than vaginal soft gelatin capsules both treatments were well tolerated.

In vitro inhibitory activity of human vaginal lactobacilli against pathogenic bacteria associated with bacterial vaginosis in Kenyan women.

Lactobacilli have been shown to inhibit in vitro growth of many pathogens and have been used as probiotics to treat a broad range of gastrointestinal and/or vaginal disorders. We sought to determine the in vitro inhibitory potential of lactobacilli of vaginal origin to some bacteria associated with bacterial vaginosis (BV), to characterize the inhibitory substances produced by these lactobacilli and to assess H2O2 production. Vaginal specimens were obtained by swabbing the lateral vaginal walls from 107 women two months following BV treatment. One hundred and fifty eight Lactobacillus spp. were isolated in 82 of the 107 women. Lactobacillus jensenii was the predominant strain isolated among these women (29/158; 18.4%). Among 158 culture supernatants tested for antibacterial activity against BV-associated bacteria, none inhibited the growth of Bacteroides fragilis while 23% (37/158), 28% (45/158) and 29% (46/158) inhibited the growth of Prevotella bivia, Gardnerella vaginalis and Mobiluncus spp. respectively. The lactobacilli produced supernatants with a pH range between 2.62 and 6.71; the highly acidic (pH 2-3.99) supernatants were more inhibitory to the indicator strains. There was significant reduction in the mean zones of inhibition following chemical and physical treatment of the supernatants (p = 0.0025). Acid, bacteriocins and H2O2 demonstrated potential for antagonism of the bacterial pathogens. These substances may augment each other rather that each working independently on the pathogens.

The effects of intravaginal clindamycin and metronidazole therapy on vaginal mobiluncus morphotypes in patients with bacterial vaginosis.

OBJECTIVE: The objective of this study was to compare the effects of treatments for bacterial vaginosis (BV) on vaginal Mobiluncus morphotypes. STUDY DESIGN: Analyses were performed on Mobiluncus scores from similarly conducted studies evaluating clindamycin vaginal single-dose cream (CVSDC) or metronidazole vaginal gel (MVG) in 55 patients with BV and with Mobiluncus morphotypes at baseline. RESULTS: Both treatment groups demonstrated significant reductions in Mobiluncus score. However, the Mobiluncus score at test-of-cure was lower in the CVSDC than in the MVG group (P=0.0471). More patients in the CVSDC group than in the MVG group achieved microbiologic (57.5% vs. 26.7%; P=0.04), clinical (57.5% vs. 26.7%; P=0.04), and therapeutic cures of BV (45.0% vs. 20.0%; P=0.09). CONCLUSION: Clindamycin reduces vaginal Mobiluncus morphotypes to a greater extent than metronidazole in patients with BV; this correlates with a higher BV cure rate.

Mobiluncus species in gynaecological and obstetric infections: antimicrobial resistance and prevalence in a Turkish population.

The purpose of this study was to determine the prevalence and antimicrobial resistance of Mobiluncus species isolated from specimens collected from Turkish women with gynaecological infections. Mobiluncus species were isolated on enriched Schaedler agar and RLK agar plates under anaerobic conditions. The MICs of various antibiotics were evaluated using an agar dilution procedure. The prevalence of Mobiluncus species isolated from vulvo-vaginal abscesses, endometrial smears, salpingitis and bacterial vaginosis was 2%, 4.7%, 3.8% and 49%, respectively. Mobiluncus isolates were only resistant to metronidazole (81% resistance). The isolation rate of M. curtisii was higher than M. mulieris in Turkish women with bacterial vaginosis, vulvo-vaginal abscesses, endometritis or salpingitis.

Activity of Novispirin G-10, a novel antimicrobial peptide against Chlamydia trachomatis and vaginosis-associated bacteria.

We tested the activity of Novispirin G-10, a novel antimicrobial alpha-helical octadecapeptide structurally related to cathelicidins and other innate immunity peptides, against Chlamydia trachomatis serovars L2, D, and E and three organisms associated with bacterial vaginosis (BV). The peptide's activity against C. trachomatis was measured in 48-h shell vial assays with McCoy cell targets. Exposure to 100 micro g/ml of Novispirin G-10 reduced the infectivity of serovars D and E by 99.4-100% and serovar L2 by 91.7-99.1%. At the same concentration of 100 micro g/ml, Novispirin G-10 rapidly killed >99% of Mobiluncus curtisii, Gardnerella vaginalis, and Prevotella bivia, in standard colony-forming unit (CFU) assays. Given its simple structure and relative lack of cytotoxic and hemolytic activity, Novispirin G-10 may be a useful component of microbicide preparations designed to prevent chlamydial infection and/or remediate the abnormal vaginal flora associated with BV.

Isolation of Mobiluncus species from the human vagina.

We report the results of a study concerning the characteristics of 52 strains of Mobiluncus spp. isolated from 982 vaginal secretions from patients with suspected bacterial vaginosis. 158 of these women presented the features of this bacterial infection. Of the strains isolated, 39 belonged to the species Mobiluncus curtisii, (25 of these which to M. curtisii subsp. curtisii and 14, to M. curtisii subsp. holmesii), and 13, to Mobiluncus mulieris. The vaginal isolates of Mobiluncus spp. were identified by comparing their biochemical profiles with those of the type strains M. curtisii subsp. holmesii (ATCC 35,242), M. curtisii subsp. curtisii (ATCC 35,241) and M. mulieris (ATCC 35,243). All strains of M. mulieris proved to be sensitive to the antimicrobial agents assayed, while strains of M. curtisii were seen to be resistant only to metronidazole.

Extragenital infection due to Mobiluncus mulieris. Case report and review.

Mobiluncus species are uncommonly isolated from nongenital sites. We report a case of abdominal abscess with associated Mobiluncus mulieris bacteremia and review the literature on extragenital infections due to Mobiluncus species.

Effects of Cetyltrimethylammonium naproxenate on the adherence of Gardnerella vaginalis, Mobiluncus curtisii, and Lactobacillus acidophilus to vaginal epithelial cells.

BACKGROUND AND OBJECTIVES: A decreased concentration or total disappearance of Lactobacillus acidophilus in the vagina constitutes a frequent observation in bacterial vaginosis. GOAL OF THE STUDY: Cetyltrimethylammonium naproxenate has been evaluated in vitro to detect antiadhesive properties at subinhibitory concentrations for Gardnerella vaginalis and Mobiluncus curtisii to vaginal epithelial cells (VEC). STUDY DESIGN: Bacterial strains 14C- and or 3H-labeled were tested for adherence and competition to binding sites in VECs before and after treatment at sub-MIC with cetyltrimethylammonium naproxenate. RESULTS: In control tests of adherence, G. vaginalis and M. curtisii had their maximal adhesion at pH 5.4, L. acidophilus at pH 4.4. Preincubation of G. vaginalis and M. curtisii with cetyltrimethylammonium naproxenate 2.5 mg/mL (subinhibitory concentration) at pH 5.4 reduced adherence to VECs respectively by 48.3% and 34.1%. The same treatment of L. acidophilus showed no statistically significant difference. Treatment of VECs alone did not modify adherence. Competition tests between L. acidophilus and G. vaginalis and between L. acidophilus and M. curtisii showed that, in small quantities, L. acidophilus could compete with G. vaginalis and M. curtisii for binding sites in VECs at pH 4.4, when pretreated with cetyltrimethylammonium naproxenate. At a higher pH (4.8 and 5.4), L. acidophilus in higher quantities did not compete for binding sites occupied by G. vaginalis and M. curtisii. CONCLUSIONS: Cetyltrimethylammonium naproxenate at subinhibitory concentrations modifies the adhesiveness of G. vaginalis and M. curtisii to VECs, reducing it by 48.3% and 34.1%, respectively. Adhesion of L. acidophilus to VECs is not impaired by pretreatment with cetyltrimethylammonium naproxenate at pH 4.4, even if they are in low number and compete for binding sites against pathogens. At higher pH levels, L. acidophilus did not compete for binding sites occupied by G. vaginalis and M. curtisii.