Assessing the Efficacy of Clotrimazole and Metronidazole Combined Treatment in Vaginitis: A Meta-Analysis.

Objective: This meta-analysis aims to assess the efficacy of combining clotrimazole and metronidazole in the treatment of mixed infectious vaginitis (VA). The goal is to provide clinical guidance for future medication strategies. Methods: We conducted a comprehensive search of the literature database for studies involving the use of clotrimazole combined with metronidazole in the treatment of mixed infectious VA. After rigorous screening, eligible studies were subjected to meta-analysis using RevMan 5.3 software. Outcome measures included cure rates, recurrence rates, and the incidence of adverse reactions. Results: Six randomized controlled trials (RCTs) were included, comprising 160 patients in the test group (treated with clotrimazole combined with metronidazole) and 160 patients in the control group (treated with alternative regimens). All selected studies were of high quality and possessed significant reference value. Meta-analysis results indicated that, in comparison to the control group, the test group exhibited a comparable incidence of adverse reactions (P > .05), higher cure rates, increased treatment satisfaction, and a lower recurrence rate (P < .05). Conclusions: The combination of clotrimazole and metronidazole is an effective treatment option for mixed infectious vaginitis, thus warranting recommendation.

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.

Inhibition of Candida albicans and induced vaginitis by sapindus water extract.

In this study, water extract of Sapindus mukorossi Gaertn. pericarps against Candida albicans was evaluated through in vitro and in vivo studies. The most abundant active ingredient was triterpenoid saponins determined by UPLC-TOF-MS analysis. The minimum inhibitory concentration (MIC) was 0.039 mg/mL by using agar double dilution methods. The percentage of inhibition was 93.07% when C. albicans was treated for 4 h using a 1 mg/mL in vitro dose. A vaginitis model was developed by infecting mice with C. albicans. The fungal burden was tracked, which indicated that 10 mg/mL triterpenoid saponins reduced fungal quantity ranging from 3.0 to 1.84 Log CFU/100 µL. Moreover, the subsequent studies regarding four biomarkers with an enzyme-linked immunosorbent assay were conducted. It was confirmed that interleukin IL-1ß, IL-6, IL-8, and lactate dehydrogenase (LDH) were lower than untreated group, and vaginal pathology was significantly improved in tissue sections.

Efficacy and safety of three plant extracts based formulations of vagitories in the treatment of vaginitis: a randomized controlled trial.

Aim There are more and more herbal preparations that are used for the purpose of treatment and improvement of the clinical manifestation of vaginitis not only by patients themselves, but also by healthcare professionals. Plant species, St. John's wort, chamomile, calendula, yarrow, shepherd's purse and tea tree oil are all well known for their anti-inflammatory, antimicrobial and wound healing activity. This paper presents the results of a clinical study in which three herbal formulations/vagitories, based on extracts of St. John's wort, chamomile, calendula, yarrow, shepherd's purse and tea tree oil, were investigated for their effectiveness on vaginitis. Methods This was a randomized controlled clinical study that included 210 women with diagnosed vaginitis. Patients were divided into two basic groups, women in reproductive period and postmenopausal period. Three subgroups including 30 patients each received one of the three vagitorie formulations for 5 days, after which the effects on subjective and objective symptoms were monitored. Results Three types of vagitories based on plant extracts had a positive effect in the treatment of vaginitis. Vagitories based on tea tree oil showed better efficiency compared to vagitories with St. John's wort and vagitories based on extracts of five plants. Women in postmenopausal group reported better tolerability of St. John's wort-based and five herbs-based vagitories compared to tea tree oil based vagitories. Conclusion Investigated vagitories showed a positive effect on both objective and subjective symptoms of vagitnis. No serious side effects were reported.

Effect of a novel herbal vaginal suppository containing myrtle and oak gall in the treatment of vaginitis: a randomized clinical trial.

BACKGROUND: Uncomplicated infections such as candidiasis, bacterial vaginosis (BV), or trichomoniasis are easy to diagnose and treat. However, about 8% of patients will have a more complicated course with failure to respond to treatment or rapid recurrence of symptoms. There are many suggestions in Traditional Persian Medicine like myrtle (Myrtus communis L.) and oak gall (Quercus infectoria G.Olivier) for treatment of vaginitis. OBJECTIVES: A clinical trial was designed to assess the efficacy of a novel herbal suppository, containing myrtle and oak gall (MOGS) in treatment of vaginitis. METHODS: In a parallel randomized clinical trial, 120 women with vaginitis were randomly assigned to MOGS, metronidazole, or placebo. Formulation was simulated from traditional Persian manuscripts and MGOS was prepared after pharmaceutical optimization processing as well as quantification of gallic acid by HPLC. The study was double-blind for MOGS and placebo and single-blind for metronidazole group. RESULTS: MOGS effectively improved vaginal discharge (p = 0.024 for BV and 0.018 for trichomoniasis) and pH (compared to placebo (p = 0.013) and metronidazole (p = 0.001)). Both MOGS and metronidazole could reverse whiff test. Metronidazole was the best medication for making Nugent score negative (p = 0.005) as well as the best therapy according to laboratory findings to treat BV in comparison with placebo (p = 0.021). While for trichomoniasis, MOGS could improve the disease more successfully (p = 0.001). Both MOGS and metronidazole treated mixed vaginitis (p = 0.002). CONCLUSION: MOGS would be a chance for developing new treatment for trichomoniasis.

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.

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.

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.

Antimicrobial Potential of Rosmarinus officinalis Commercial Essential Oil in the Treatment of Vaginal Infections in Pregnant Women.

Treating inflammatory conditions .such as vaginosis, vaginitis, and vulvovaginitis in pregnancy is- a special problem due to limitations. of available drugs. However, possible treatment options can be found also in naturally originated products, such as essential oils (EOs) of different plants. The aim of this study was to evaluate in -vitro antimicrobial and toxic activities of the commercial EO of Rosmiarinus officinalis L. (Lamiaceae) against five Gram-positive and Gram-negative bacterial strains and two Candida strains obtained from pregnant women with Vaginal infection. Gas chromatography-mass spectrometry of the tested EO revealed oxygenated monoterpenes to be the major ingredients, while microdilution assay showed the highest activity on Staphylococcus aureus II strain at 6.2 mg/mL. After 24 hours, toxicity was determined at 19.4 mg/mL on Artemia salina nauplii. The obtained results show this EO to be a promising alternative therapy for vaginal infections, although further toxicity and safety research is required.

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.

New strategies for local treatment of vaginal infections.

Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route.

[Clinical observation on treatment of mycotic vaginitis with Sophora gel combined with Fluconazole capsules].

Mycotic vaginitis is a common and frequently-occurring gynaecopathia and easy to attack repeatedly, so painful to patients. In this study, the authors observed the clinical efficacy of Sophora gel combined with Fluconazole capsules in treating mycotic vaginitis, in order to seek an effective method for treating mycotic vaginitis. Totally 85 patients with mycotic vaginitis treated in our hospital between December 2012 and July 2014 were randomly divided into the treatment group (43 patients) and the control group (42 patients). The treatment group was given vaginally Sophora gel (one piece every night for 14 days) and orally Fluconazole capsules (150 mg, once every three days, four times in total); The control group was only administered with Fluconazole capsules. The total efficacy, cure rate, recurrence rate and clinical symptom improvements of the two groups were observed. The results show that the total efficacy, the cure rate and the recurrence rate of the treatment group vs. the control group were respectively 97.7%, 90.7% and 2.6% vs. 83.3%, 71.4% and 20.0%, with statistical significance in their differences (P < 0.05). The treatment group showed reduced leucorrhea, pruritus vulvae disappearance and earlier mucosal hyperemia disappearance than the control group, with statistical significance in their differences (P < 0.05). In conclusion Sophora gel combined with Fluconazole capsules can improve antifungal activity of drugs, relieve clinical symptoms, shorten the course of disease, enhance the cure rate and reduce the recurrence rate; So this therapy can be widely applied in clinic.

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.

[The pharmacodynamic research on fuxiye, a Chinese herbal lotion for external wash].

OBJECTIVE: To observe antisepsis, anti-swelling, and therapeutic effects of Fuxiye (FXY), a Chinese medical lotion for external wash in treating vaginitis model rats. METHODS: The cervicitis rat model was induced by agar plate diffusion, ear auricle swelling induced by dimethylbenzene, and chemical stimulus. The in vitro antibiotic actions of FXY were observed. Besides, its effects on the swelling and inflammation in model rats were also observed. RESULTS: FXY at 25 mg/mL could completely inhibit the growth of Pseudomonas aeruginosa, Escherichia coli, pyogenic Streptococcus, and Streptococcus agalactiae. FXY at 50 mg/mL could completely inhibit the growth of Staphylococcus aureus and Candida albicans. It obviously restrained dimethylbenzene induced ear auricle swelling. It significantly alleviated cervicitis induced by chemical stiumli. CONCLUSION: FXY showed better effects on antisepsis, anti-inflammation, and treating cervicitis.

Arginine inactivates human herpesvirus 2 and inhibits genital herpesvirus infection.

Arginine, among the amino acids, has demonstrated unique properties, including suppression of protein-protein interactions and virus inactivation. We investigated the effects of arginine on the infectivity of human herpesvirus 2 (HHV-2) and the potential application of arginine as a chemotherapeutic agent against genital herpes. Arginine directly inactivated HHV-2 and characterization of the inactivation demonstrated that 1 M arginine at pH 4.3 inactivated the virus more efficiently compared to 0.1 M citrate or 1 M sodium chloride, indicating that neither acidic pH nor ionic strength alone is sufficient for virus inactivation. The effect of arginine was rapid and concentration-dependent. Although virus inactivation was efficient at an acidic pH, arginine inactivated the virus even at a neutral pH, provided that a higher arginine concentration and prolonged incubation time were used. In addition, arginine suppressed the multiplication of HHV-2 under the conditions at which its effect on cell viability was insignificant. Pilot mouse model studies revealed a marked suppression of death by arginine when the mice were infected with HHV-2 through the vaginal route, followed by an intermittent application of acidic arginine by vaginal instillation.

The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause.

PURPOSE: The quality of life in postmenopause is seriously affected by the symptoms related to vaginal atrophy. To evaluate in a 3-month, prospective, randomized, double blind, study whether vaginal suppositories containing genistein might improve genital symptoms, colposcopical and cytologic findings or modify DNA cytometric features in postmenopausal women affected by vaginal atrophy, in comparison with vaginal suppositories containing hyaluronic acid (HA). METHODS: A total of 62 postmenopausal women were randomly assigned to receive intravaginally 97 µg of genistein (group A, n = 31) or 5 mg of HA (group B, n = 31) daily for 15 days continuously/month for 3 months. Vaginal and cervical smear, colposcopy, vaginal biopsy were performed before and at the end of the study. Maturation value (MV) was calculated. Flow cytometric analysis of DNA ploidy (DI) and S-phase fraction (SPF) were performed. RESULTS: After 90 days of study, a significant improvement was obtained in genital symptoms, colposcopy scores and MV (p < 0.001) in both groups; the improvement obtained by genistein was more effective especially regarding genital score (p value between groups 0.001). No significant change was found in SPF value and DI. CONCLUSION: Both treatments improved genital symptoms, colposcopical features and MV, although genistein was more effective on genital score. Both treatments did not significantly influence flow cytometry parameters, although genistein showed slight decrease in DI, with a normalization of the aneuploid content present in some cases that could represent an additional application of intravaginal phytoestrogen therapy, providing an alternative therapy of vaginal atrophy in postmenopausal patients. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.

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.

Synergistic anti-candidal activity of tetrandrine on ketoconazole: an experimental study.

With the widespread use of azoles, drug resistant Candida albicans strains are increasing. The study examined the synergism of tetrandrine (TET) on ketoconazole (KCZ) candidacidal activity. The protocol M27-A2 of the Clinical and Laboratory Standards Institute (CLSI) was adopted and the minimum inhibitory concentrations (MICs) were determined for KCZ alone and in combination with a TET level that was noncytotoxic for C. albicans strains CA-1 through CA-17, with no CA-10. Colony counting techniques were used to construct time-kill curves. CA-15 was used to build the mouse candidal vaginitis model. After randomization, drugs were administered vaginally once daily from days 3-10 (both KCZ and TET were 26 mg/kg/day and 13 mg/kg/day, respectively, administered in different combinations). Mouse vaginal lavage fluid was obtained at days 2, 6, and 11 after inoculation for fungal load analysis, and vaginal tissue was obtained for pathological examination. MICs of KCZ alone and combined with 30 microg/mL TET for the C. albicans strains were 1-32 microg/mL and 0.0038-0.2500 microg/mL, respectively ( T = 24.624, p = 0.000). Time-kill curves showed that at 48 h the viable cell counts of strains treated with KCZ + TET were at least 2 log(10) CFU/mL lower compared to strains treated with corresponding doses of KCZ (p = 0.000). At day 6, the fungal load in the KCZ 26 mg/kg/day + TET 26 mg/kg/day mice was significantly lower than the KCZ 26 mg/kg/day mice (1.17 +/- 1.17 x 10(4) CFU/mL and 9.33 +/- 3.08 x 10(4) CFU/mL, respectively, p = 0.000). Mucosal and submucosal fungal clearances were complete and vaginal mucosal edema was slight with minimal inflammatory cell infiltration. We conclude that noncytotoxic doses of TET synergistically enhance KCZ candidacidal activity in vitro and in vivo.