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This protocol is a prospective, interventional, randomized, double-blind, placebo controlled longitudinal study designed to investigate the microbiomic and immunologic perturbations that lead to vulvovaginal candidiasis (VVC) in women who receive antibiotics. VVC is the most common fungal infection affecting women. Although asymptomatic vaginal Candida colonization occurs in ~10-20% of healthy women, ~75% of women will experience at least one episode of symptomatic VVC during their lifetime. Nonetheless, the local mucosal factors that allow Candida to convert from a commensal organism to an opportunistic pathogen are not well defined. Antibiotic use (particularly beta-lactams) is a well-recognized risk factor for the development of VVC in healthy women, suggesting that alterations in the endogenous vaginal microbial flora results in deregulation of local mucosal anti-Candida immune responses. However, which commensal vaginal microbiota are important for protection against Candida infection, and the mechanism(s) whereby vaginal microbiota influence the local mucosal immune response against Candida, remain unknown.
To address these questions, healthy women of reproductive age will receive a 10-day course of amoxicillin (a broad-spectrum, beta-lactam antibiotic) or a placeboand will undergo vaginal sampling for microbiomic and immunologic analyses before, during and after antibiotic administration over a 90-day period. The hypothesis of this study is that women who develop amoxicillin-associated VVC will have a characteristic microbiomic profile (as compared to women with absent or asymptomatic Candida colonization) with associated impairment in local mucosal anti-Candida immune responses. The aim of this study is to elucidate the vaginal microbiomic and immunologic perturbations that allow Candida to transition from commensal to pathogen in the context of antibiotic administration. A better understanding of the role of specific microbiota and mucosal immune factors in averting Candida infection may lead to the design of targeted preventive and/or therapeutic interventions against VVC.
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Inclusion and exclusion criteria
Females 18-40 years of age must meet the following criteria to be eligible for participation in this study:
Participation of Women:
Contraception:
Because menstruation is known to affect the vaginal microbiome and because oral contraceptives produce predictable menstrual cycles, subjects must be on oral contraceptives in order to be eligible for the study. Additionally, since amoxicillin may theoretically reduce the efficacy of oral contraceptives, subjects must agree to use an additional form of contraception (barrier method, abstinence) while receiving the study drug.
EXCLUSION CRITERIA:
A subject will not be eligible if she has any of the following:
Pregnancy
Breastfeeding
Known allergy to beta-lactam antibiotics (e.g., penicillin)
Body mass index (BMI) greater than or equal to 35 or less than or equal to 18 at screening visit
Vital signs outside of acceptable range at screening visit (i.e. blood pressure > 160/100, oral temperature > 100 degrees F, pulse > 100)
Primary or acquired immunodeficiency, including Human Immunodeficiency Virus (HIV) (diagnosed via an FDA-approved test)
Hepatitis C seropositivity or positive Hepatitis B surface antigen
Chronic, clinically significant (requiring on-going medical management or medication) pulmonary, cardiovascular, dermatologic, endocrine, gastrointestinal, hepatic or renal functional abnormality, as determined by medical history and physical examination and/or laboratory testing (Complete blood count [CBC] with differential, Acute Care Panel, Hepatic Panel)
Active malignancy or history of malignancy for which there is not reasonable assurance of sustained cure
Major surgery of the gastrointestinal tract, including any major bowel resection at any time, with the exception of cholecystectomy and appendectomy, in the past five years
Genitourinary/Gynecologic conditions, including:
Chronic smokers and subjects who use smokeless tobacco products (due to known effects of tobacco on the oral microbiome)
Exposures to the following agents (which could affect the microbiome) within 6 months prior to sampling:
Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent
Creatinine clearance < 50 mL / min
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Data sourced from clinicaltrials.gov
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