RESUMO
There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman's lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease.
Assuntos
Interações entre Hospedeiro e Microrganismos/fisiologia , Metabolômica/métodos , Microbiota/fisiologia , Mucosa/microbiologia , Vagina/microbiologia , Feminino , Humanos , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Mucosa/imunologia , Mucosa/metabolismo , Vagina/imunologia , Vagina/metabolismoRESUMO
Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a novel avenue to modulate and protect the vaginal microbiota.
Assuntos
Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Sistemas de Liberação de Medicamentos/efeitos adversos , Ácido Láctico/administração & dosagem , Ácido Láctico/efeitos adversos , Microbiota/efeitos dos fármacos , Vagina/microbiologia , Administração Intravaginal , Adulto , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Mucosa/microbiologia , Pré-Menopausa/efeitos dos fármacos , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/microbiologia , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to identify the aerobic bacteria of the preputial and vaginal microbiota in owl monkeys that have been raised in captivity and to evaluate the antimicrobial susceptibility of these bacteria by gender and social organization. METHODS: Thirty clinically healthy Aotus azarai infulatus were used. A total of 134 samples were collected, 60 from the preputial mucosa and 74 from the vaginal mucosa. An automated system of bacterial identification was used. RESULTS AND CONCLUSIONS: Staphylococcus intermedius and Proteus mirabilis were the microorganisms that were most frequently identified according to gender and social organization. The antimicrobial susceptibility of the isolated gram-positive bacteria was similar in both sexes. However, the gram-negative strains had some differences. The aerobic bacterial population of the vaginal and preputial microbiota is similar in owl monkeys, and there are no differences in the number and bacterial species according to sex and social organization.
Assuntos
Aotidae/microbiologia , Pênis/microbiologia , Vagina/microbiologia , Animais , Feminino , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Masculino , Metagenoma , Testes de Sensibilidade Microbiana , Modelos Animais , Mucosa/microbiologia , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/isolamento & purificação , Comportamento Sexual Animal , Staphylococcus intermedius/efeitos dos fármacosRESUMO
BACKGROUND: Menstrual tampons are available in a range of absorbencies to allow women to use the product most appropriate to their needs. This study assessed the safety of an ultra absorbency (15 g to 18 g) tampon compared with a currently marketed super-plus absorbency (12 g to 15 g) tampon as a control. METHODS: Healthy women age 18-45 years (n = 95) were enrolled in this single-blind, crossover study. Subjects used, in random order, the experimental tampon during one menstrual cycle and the control tampon during the other. Subjects were also randomly assigned to receive either vaginal microbial assessments for determination of the presence and density of Staphylococcus aureus (n = 35) or colposcopic examinations for assessment of changes in the vaginal mucosa (n = 60). Data on comfort and acceptability of the tampons were collected by using diaries and questionnaires completed by the subjects in both groups. RESULTS: Twenty-eight women in the microbial assessment group and 43 in the colposcopic examination group completed the study; these subjects made up the primary analysis population. No differences in isolation frequency or cell density of S. aureus or in vaginal mucosal changes were observed with the experimental tampon in comparison with the control tampon. No reported adverse events were attributed to the experimental tampon. Both tampons received positive comfort ratings. CONCLUSIONS: Based upon microbial assessments, colposcopic examinations, adverse events, and subject reporting of comfort, the ultra absorbency tampon is similar in safety profile to the currently marketed super plus absorbency tampon.
Assuntos
Qualidade de Produtos para o Consumidor , Produtos de Higiene Menstrual/normas , Adulto , Colposcopia , Estudos Cross-Over , Feminino , Humanos , Ciclo Menstrual/fisiologia , Produtos de Higiene Menstrual/efeitos adversos , Produtos de Higiene Menstrual/classificação , Pessoa de Meia-Idade , Mucosa/microbiologia , Satisfação Pessoal , Método Simples-Cego , Staphylococcus aureus/isolamento & purificação , Inquéritos e Questionários , Vagina/microbiologia , Adulto JovemRESUMO
We report on the correlation of the outcomes for two cohorts of patients who had been treated for candidemia (126 episodes) or oropharyngeal candidiasis (110 episodes) with various doses of fluconazole and the MIC of fluconazole obtained by using the EUCAST standard for fermentative yeasts. Of 145 episodes caused by an isolate with a fluconazole MIC < or =2 mg/liter, 93.7% (136 of 145) responded to fluconazole treatment. The response for those infected with a strain with a MIC of 4 mg/liter was 66% but reached 100% when the dose was greater than 100 mg/day, whereas the response for those infected with strains with MICs > or =8 mg/liter was only 12%. Hence, a MIC of 2 mg/liter or 4 mg/liter was able to predict successful treatment. A cure rate of 93.9% (140 of 149) was achieved when the dose/MIC ratio was > or =100 but fell to 14.6% (16 of 109) when the ratio was less. The dose/MIC required to achieve a response rate of 50% (the 50% effective concentration) was 43.7 for the cohort of patients with oropharyngeal candidiasis. Classification and regression analysis indicated that a dose/MIC of 35.5 was the threshold for the prediction of cure or failure. However, an increase in exposure above this threshold further increased the probability of cure, and all patients were cured when the dose/MIC exceeded 100. Monte Carlo simulations showed a probability of target attainment of 99% at MICs < or =2 mg/liter and a pharmacodynamic target of a dose/MIC ratio of 100, which was equivalent to an unbound fraction of the fluconazole area under the curve versus the MIC of 79.
Assuntos
Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacocinética , Área Sob a Curva , Candidíase/microbiologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Fluconazol/farmacocinética , Fungemia/microbiologia , Infecções por HIV/complicações , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Mucosa/microbiologia , Orofaringe/microbiologia , Análise de Regressão , Espanha , Resultado do TratamentoRESUMO
Certain respiratory tract infections can be transmitted by hand-to-mucous-membrane contact, inhalation, and/or direct respiratory droplet spray. In a room occupied by a patient with such a transmissible infection, pathogens present on textile and nontextile surfaces, and pathogens present in the air, provide sources of exposure for an attending health-care worker (HCW); in addition, close contact with the patient when the latter coughs allows for droplet spray exposure. We present an integrated model of pertinent source-environment-receptor pathways, and represent physical elements in these pathways as "states" in a discrete-time Markov chain model. We estimate the rates of transfer at various steps in the pathways, and their relationship to the probability that a pathogen in one state has moved to another state by the end of a specified time interval. Given initial pathogen loads on textile and nontextile surfaces and in room air, we use the model to estimate the expected pathogen dose to a HCW's mucous membranes and respiratory tract. In turn, using a nonthreshold infectious dose model, we relate the expected dose to infection risk. The system is illustrated with a hypothetical but plausible scenario involving a viral pathogen emitted via coughing. We also use the model to show that a biocidal finish on textile surfaces has the potential to substantially reduce infection risk via the hand-to-mucous-membrane exposure pathway.