Accurate 16S Absolute Quantification Sequencing Revealed Vaginal Microecological Composition and Dynamics During Mixed Vaginitis Treatment With Fufang FuRong Effervescent Suppository.

Background: The diagnosis and treatment of mixed vaginitis are more complicated than single pathogenic infections, and there may be adverse reactions and several contraindications to conventional antibiotic therapy. Therefore, this study aimed to evaluate the preliminary effects of Fufang Furong Effervescent Suppository for the management of aerobic vaginitis (AV) mixed with bacterial vaginosis (BV) using Accurate 16S absolute quantification sequencing (Accu16S). Methods: In the present randomized, blind, multi-center clinical trial, women (20 to 55 years) who had received a diagnosis of AV+BV were randomly assigned into clindamycin positive control (n = 41) and Fufang Furong Effervescent Suppository (n = 39) groups. The follow-up occurred in three time periods (V1: -2~0 days; V2: 15-17 days; V3: 40 ± 3 days). At each visit, two vaginal swabs, one for clinical evaluation and one for laboratory examination, were taken from each patient. The Nugent score, Donders' score, drug-related complications, recurrence rates, and microecological changes of vaginal swabs were assessed in the time three periods. Results: At baseline, the two groups were similar in frequency of presentation with vaginal burning, odor, abnormal discharge, and itching. No meaningful differences in Nugent and Donders' scores were detected between the two groups at stage V2 (Nugent: p = 0.67; Donders': p = 0.85) and V3 (Nugent: p = 0.97; Donders: p = 0.55). The Furong group presented fewer complications compared to the Clindamycin group. However, this difference was not statistically significant (p = 0.15). Additionally, Accu16S indicated that the total abundance of bacteria in both groups sharply decreased in stage V2, but slightly increased in V3. In stage V3, the absolute abundance of Lactobacillus in the Furong group was considerably higher compared to untreated samples (p < 0.05). On the other hand, no momentous increase was detected in the Clindamycin group (p > 0.05). Conclusion: Fufang Furong Effervescent Suppository can be as effective as clindamycin cream in the management of AV+BV while may restore the vagina microecosystem better.

Vaginitis: Review on Drug Resistance.

Female genital tract infections have a high incidence among different age groups and represent an important impact on public health. Among them, vaginitis refers to inflammation of the vulva and/or vagina due to the presence of pathogens that cause trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Several discomforts are associated with these infections, as well as pregnancy complications and the facilitation of HIV transmission and acquisition. The increasing resistance of microorganisms to drugs used in therapy is remarkable, since women report the recurrence of these infections and associated comorbidities. Different resistant mechanisms already described for the drugs used in the therapy against Trichomonas vaginalis, Candida spp., and Gardnerella vaginalis, as well as aspects related to pathogenesis and treatment, are discussed in this review. This study aims to contribute to drug design, avoiding therapy ineffectiveness due to drug resistance. Effective alternative therapies to treat vaginitis will reduce the recurrence of infections and, consequently, the high costs generated in the health system, improving women's well-being.

Systematic analysis of bacteriostatic mechanism of flavonoids using transcriptome and its therapeutic effect on vaginitis.

The flavonoids in Ageratum conyzoides L. have been used in traditional medicine due to its anti-inflammatory and antibacterial properties. However, the specific mechanism of its antibacterial effect, and the potential therapeutic effect on vaginitis have not been well explained. The growth curves of E. coli, S. aurues, and P. aeruginosa after treatment with flavonoids were measured. The influences of flavonoids on the conductivity of bacterial culture medium and exudation of bacterial nucleic acid were also detected. Transcriptomics analysis was applied to analyze the potential mechanism of flavonoids. Flavonoids significantly suppressed the growth curves of E. coli, S. aurues, and P. aeruginosa, and increased the conductivity of bacteria and nucleic acid exudation. Transcriptomics analysis indicated that flavonoids could suppress bacteria by affecting the transcription and metabolism pathways. The obvious therapeutic effect of flavonoids on bacterial vaginitis was also observed. This study systematically analyzed the bacteriostatic mechanism of flavonoids, which should be helpful to develop new drugs based on the bacteriostatic effect of flavonoids.

Use of probiotics in medical devices applied to some common pathologies.

Probiotics, defined as "living microorganisms that, whether ingested in useful amount, may have beneficial effects on human body", are widely used in various products for human use, such as dietary supplements, medical devices and pharmaceutical products. The European Directive on medical devices (MDs) (DDM 93/42), also includes those MDs containing live microorganisms, particularly probiotics, that may have various destinations of use, including that of assisting the therapy of several human pathologies. In this brief note we analyzed the use of probiotics in MDs and how probiotics administration could represent one of the new frontiers of scientific research on the prevention and treatment of various diseases. We'll analyze the literature on probiotics based MDs, to review their major targets in the therapy of some of the most common human pathologies: bacterial vaginosis and vaginitis, atopic dermatitis, infantile colic, obesity, type 2 diabetes, and pharyngotonsillitis.

Effect of pea protein plus grape seed dry extract on a murine model of Candida albicans induced vaginitis.

AIM: The objective of this research was to evaluate the antifungal properties of the association between grape seed and pea by using a nonpharmacological medical device that contains them. MATERIALS & METHODS: A murine model of vulvovaginal candidiasis, induced by Candida albicans infection, was used. RESULTS: We showed that topical treatment with the device significantly reduced the fungal burden in vagina and preserved vagina tissue architecture from C. albicans infection. CONCLUSION: We can support the potential beneficial effect of the association between grape and pea extract present in the medical device. Together these results supported this device as a favorable antifungal agent and a promising synergist with fluconazole in the clinical management of vulvovaginal candidiasis caused by C. albicans biofilms.

A Designed Tryptophan- and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis.

New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV-NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs.

Photodynamic therapy has antifungal effect and reduces inflammatory signals in Candida albicans-induced murine vaginitis.

BACKGROUND: Vaginal candidiasis (VC) is a disease that affects thousands of women of childbearing age, mainly caused by Candida albicans fungus. Photodynamic therapy (PDT) uses photosensitizing substances that are nontoxic in the dark, but able to produce reactive oxygen species when they are subjected to a light source. In this work our purpose was to investigate PDT effects on fungal burden and inflammatory cells in a murine model of C. albicans-induced vaginal candidiasis. METHODS: Female BALB/c mice 6-10 weeks were estrogenized and maintained in this state during all experiment. After 72h, mices were inoculated intravaginally (IV) with 20µL of 2×10(5)C. albicans cells suspension. Mice were separated into 5 groups after five days: H (healthy), PBS (control), laser, MB (methylene blue) and PDT. PDT and MB groups received IV 20µL solution with 1mM of MB, others received PBS. PDT and laser groups were irradiated with a red laser (100mW, 660nm) in one (36J, 6min) or two sessions (18J, 3min). After the end of treatment, mice were submitted to microbiological and histomorphometric analysis with ImageJ software. Data were plotted by mean values and standard deviations of CFU/mL and percentage of inflammatory cells area. ANOVA and Bonferroni post-test were used and data were considered significant when p<0.05. RESULTS: PDT significantly reduced C. albicans after the two tested protocols, however, percentage area of inflammatory cells was significantly reduced just with two sessions of PDT. CONCLUSIONS: PDT with MB and red laser is a promising therapy for VC. It is able to reduce fungal infection in biofilm and inflammatory signals associated with VC in a murine model of vaginitis.

A comprehensive review of vaginitis phytotherapy.

To overview phytotherapy of vaginitis in order to identify new approaches for new pharmacological treatments. All related literature databases were searched for herbal medicinal treatment in vaginitis. The search terms were plant, herb, herbal therapy, phytotherapy, vaginitis, vaginal, anti-candida, anti-bacterial and anti-trichomonas. All of the human, animal and in vitro studies were included. Anti-candida, anti-bacterial and anti-trichomonas effects were the key outcomes. The plants including carvacrol, 1,8-cineole, geranial, germacrene-D, limonene, linalool, menthol, terpinen-4-ol and thymol exhibited anti-candida effects. A very low concentration of geranium oil and geraniol blocked mycelial growth, but not yeast. Tea tree oil including terpinen-4-ol, alpha-terpinene, gamma-terpinene and alpha-terpineol showed anti-bacterial, anti-fungal and anti-protozoal properties against trichomonas. Allium hirtifolium (persian shallot) comparable to metronidazole exhibited anti-trichomonas activity due to its components such as allicin, ajoene and other organosulfides. The plants having beneficial effects on vaginitis encompass essential oils that clear the pathway that future studies should be focused to standardize theses herbs.

Determining the cause of vulvovaginal symptoms.

Both patients and clinicians may incorrectly diagnose vulvovaginitis symptoms. Patients often self-treat with over-the-counter antifungals or home remedies, although they are unable to distinguish among the possible causes of their symptoms. Telephone triage practices and time constraints on office visits may also hamper effective diagnosis. This review is a guide to distinguish potential causes of vulvovaginal symptoms. The first section describes both common and uncommon conditions associated with vulvovaginitis, including infectious vulvovaginitis, allergic contact dermatitis, systemic dermatoses, rare autoimmune diseases, and neuropathic vulvar pain syndromes. The focus is on the clinical presentation, specifically 1) the absence or presence and characteristics of vaginal discharge; 2) the nature of sensory symptoms (itch and/or pain, localized or generalized, provoked, intermittent, or chronic); and 3) the absence or presence of mucocutaneous changes, including the types of lesions observed and the affected tissue. Additionally, this review describes how such features of the clinical presentation can help identify various causes of vulvovaginitis.

A universal combination treatment for vaginitis.

BACKGROUND: We compared a novel vaginal tablet consisting of 100 mg of clotrimazole and 100 mg of metronidazole ('Clo-Met') to a 100-mg clotrimazole tablet in the treatment of vaginitis. METHODS: A multicenter, double-blind, randomized controlled study. Women with vaginal discharge and diagnosed as suffering from vaginitis caused by Trichomonas vaginalis, bacterial vaginosis or Candida albicans, or any combination of the three, and who had not received treatment for vaginitis during the previous month, were studied. RESULTS: 165 patients were enrolled into the study--84 into the combined therapy group, and 81 into the clotrimazole group. In women with Candida vaginitis, Clo-Met was more effective than clotrimazole treatment (p < 0.012 and p < 0.05, respectively). CONCLUSION: A combination vaginal tablet consisting of clotrimazole and metronidazole is therapeutically effective in candidal vaginitis. The effectiveness of Clo-Met on bacterial vaginosis, T. vaginalis infection as well as on vaginal infections due to a combination of these microorganisms should be studied further.

[Etiologic role of Corynebacterium non diphtheriae in patients with different pathology].

Bacteriologic examination of 1589 patients showed that, aside from C. diphtheriae, 11% of acute upper respiratory tract infections were caused by other Corynebacterium species. Such bacteria can cause infections of various localizations (bronchitis, pyelonephritis, urethritis, colpitis, dermatitis, arthritis, etc.). C. pseudodiphtheriticum and C. xerosis were isolated from clinical specimens most frequently. Corynebacterium spp. have adhesive, hemolytic, hemagglutinating, and neuraminidase activity; some of them are highly pathogenic. The most virulent, were following species: C. diphtheriae, C. pseudotuberculosis, C. urealyticum, and C. ulcerans. Corynebacterium non diphtheriae were frequently isolated from clinical specimens in association with staphylococci and streptococci. In such cases, factors of pathogenicity and resistance to antibiotics were more pronounced. Strains isolated with association with other bacteria have lost susceptibility to tetracycline, oleandomycin, penicillin, and erythromycin. It is important to be vigilant about bacteria from Corynebacterium genus in clinical settings, and thoroughly study their biologic characteristics, especially in immunocompromised patients.

Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy.

Twelve women with vaginal Candida krusei infection were evaluated. In vitro antifungal susceptibility testing and molecular typing were performed. Patients infected with C. krusei frequently had refractory vulvovaginal signs and symptoms that were otherwise indistinguishable from vaginitis due to other yeasts. Patients were 32-63 years old and had previously received multiple courses of antimycotic agents, including fluconazole and miconazole. The most active azole in vitro was clotrimazole, with a 90% minimum inhibitory concentration of 0.25 microg/mL. Four of 6 patients treated with boric acid had clinical and mycological cure. Two dominant genotypes of C. krusei were identified via contour-clamped homogenous electrical field analysis. No major genotypic change was observed in successive isolates from the same patient in most cases, suggesting that these refractory cases were relapses. C. krusei is a rare but important cause of refractory vaginitis and is unique because of its intrinsic resistance to fluconazole.

[Antifungal susceptibility testing in chronically recurrent vaginal candidosis as basis for effective therapy]. / Resistenzbestimmungen bei Erregern chronisch rezidivierender Vaginalcandidosen als Voraussetzung für eine effektive Therapie.

The chronically recidivist vulvo-vaginal candidiasis is one of the most stubborn problematic diagnosis in the dermatology and gynaecology ward. Prognosis and therapy are primarily determined by the causative micro-organism and the interaction of the fungal species with the currently available antifungal agents. Objective of the study was the investigation of vaginal yeast isolates from patients with chronically recidivist vaginal candidiasis against 8 antifungal agents with the aim of optimising the standard therapy with azole antifungal agents and assessment of alternative therapy schemes. 55 clinical isolates (Dermatology, Charité) of 40 patients were tested by microdilution according to DIN 58940-84. Species differentiation and identification was performed by Fourier-Transform Infrared Spectroscopy (FTIR). In the result Candida glabrata was the predominant causative agent for the recidivist vaginal candidiasis. MIC-mode values for C. glabrata were: fluconacole 32 micrograms/ml, itraconacole 1 microgram/ml, ketoconacole 1 microgram/ml, amphotericine B, voriconacole 0.03 microgram/ml, amphotericin B 0.5 microgram/ml, terbinafine 128 micrograms/ml, cicloproxolamine 4 micrograms/ml, 5-fluorocytosine 0.03 microgram/ml. Some strains of Patients with suboptimal introductory low doses of fluconacole showed increasing of MIC in course of therapy. Parallel resistance with itraconacole was observed in all these cases. Consecutively isolated strains could be clearly and reliably identified by FTIR. In conclusion of most importance is the initial dose adapatation of the drug used, e.g. for fluconacole 800/d p.o., when C. glabrata is the causative agent. Low dose fluconacole therapy is always unsuccessful in recurrent vaginal candidiasis and induces secondary resistance. Demonstrated high susceptibility of voriconacole, amphotericine B an 5-fluorocytosine particularly for C. glabrata may indicate of an anitmycotic therapy potential unconsidered regarding to dermatological indication up to now.

Efficacy of D0870 treatment of experimental Candida vaginitis.

In this study, oral administration of the triazole D0870 was compared to oral administration of fluconazole in the treatment of experimental vaginal candidiasis. With an estrogen-dependent murine model of Candida albicans vaginal infection, the effects of D0870 on several isolates, including fluconazole-susceptible and -resistant isolates, were tested. D0870, at doses of 0.5 and 2.5 mg/kg of body weight given once over the course of a 10-day infection, was effective in eradicating vaginitis caused by fluconazole-susceptible laboratory and clinical isolates, respectively. In contrast, a stricter treatment regimen (every 24 to 48 h) with 10 and 25 mg of fluconazole per kg was required to achieve similar reductions in vaginal fungal titers induced by the same isolates. Whereas fluconazole was consistently ineffective in infections induced by fluconazole-resistant isolates, as predicted by in vitro susceptibility tests, D0870 was effective, although a daily regimen of 25 mg/kg was required. Additional studies showed that despite the in vitro activity of D0870 against two clinical Candida glabrata isolates, neither D0870 nor fluconazole was effective at daily doses as high as 100 and 125 mg/kg, respectively. Taken together, although D0870 failed to show efficacy against experimental C. glabrata vaginitis, D0870 was superior to fluconazole in the treatment of experimental C. albicans vaginitis caused by isolates that were either susceptible or resistant to fluconazole.

Vaginitis due to Saccharomyces cerevisiae: epidemiology, clinical aspects, and therapy.

Vaginitis due to Saccharomyces species is extremely rare. Nine patients with 20 vaginal isolates of Saccharomyces cerevisiae who presented with either asymptomatic vaginal colonization or symptomatic vaginitis indistinguishable from that caused by Candida albicans are described. All patients had a history of chronic or recurrent vaginitis, and all but two had systemic or local predisposing factors. In vitro tests of antimycotic sensitivity revealed reduced susceptibility of S. cerevisiae to the majority of available azole agents, with outright resistance to fluconazole. In accordance with these findings, the clinical response to conventional topical and oral antimycotic drugs was frequently suboptimal and incomplete. Electrophoretic karyotyping of strains revealed several distinct types of S. cerevisiae; this information permitted both longitudinal follow-up and differentiation of relapse from reinfection. In three patients with recurrent vaginitis, a unique epidemiological relationship was documented between S. cerevisiae and Torulopsis glabrata, another unusual and resistant vaginal pathogen. Isolation of S. cerevisiae from the vagina of symptomatic patients should not be ignored; treatment of vaginal infection with this yeast requires selected, often prolonged therapy.