Preclinical Evaluation of Pharmaceutical Compositions and Their Components for Urinary Health

Background: The need for products that treat or prevent urinary tract infections without resort to antibiotics that may select for resistant bacterial strains has created a need to develop antibiotic-free therapeutics. Objective: To conduct an exploratory evaluation of intrinsic antimicrobial activity of a panel of compounds alone or in combination against urinary pathogens and probiotic organisms as well as their effect on biofilm formation and immune activity in infected cultured bladder epithelial cells. Results: Of the compounds tested, 1% citric acid was most consistently inhibitory to urinary pathogens as were combinations containing citric acid. Two combinations of compounds were tested and both showed antimicrobial activity when challenged with 1 × 105 bacteria/mL. The two combination products and D-mannose did not inhibit probiotic microorganisms and one composition increased the inhibitory potential of probiotic organisms. Results obtained with biofilm studies were variable, but probiotic biofilm was enhanced under some circumstances. Biofilms of some urinary pathogens were reduced by antimicrobial mixtures. A strong cytokine response was elicited when T24 bladder epithelial cells were infected for one hour with urinary pathogens and a modest reduction in cytokine response was recorded with some combinations of test compounds. Conclusion: Citric acid alone and mixtures of various compositions containing citric acid inhibited the growth and biofilm formation by 4 uropathogens. Probiotic organisms grew in the presence of mannose and citric acid-containing combinations. One of the combinations enhanced probiotic activity of Lactobacilli against uropathogens. When infecting T24 cell monolayers with uropathogens, potential modulation of inflammatory activity was demonstrated.

Current Concepts of <i>Gardnerella vaginalis</i>Biofilm: Significance in Bacterial Vaginosis

Gardnerella vaginalis (GV) has been implicated in BV development. Further, biofilm is accepted as one, if not the principle reason, for recurrent or recalcitrant BV. GV has defined virulence factors that contribute to biofilm, though more may be discovered within genomic information. Key players in genital tract microecology include GV, other species of the microbiome, and the epithelial base on which microbial interactions occur. The epithelium is influenced by various forces such as douching, smoking, diet, and estrogen: other potential factors are yet unidentified. All of these factors may contribute to bacterial vaginosis. Further, biofilms usually contain microbial species in addition to GV, and the mechanisms for supporting roles of these other species provide an opportunity for elucidation. Gaps in knowledge still exist in effective therapeutics aimed at biofilm, and better understanding of the process of bacterial quiescence, persistence, and biofilm formation is a key step in future research. Purpose: This review examines current literature for information about biofilm significance in relation to GV and bacterial vaginosis. Methods: Structured literature review.

Navigating the Third Frontier of Antimicrobial Therapy to Support Women’s Health

This paper explores one of the underappreciated reasons for lack of efficacy in certain cases of antimicrobial therapy, namely the occurrence of a non-genetic resistance to antimicrobial drugs due to a metabolic quiescence of microorganisms. This review has centered on those microorganisms of particular importance in obstetrics and gynecology and accordingly has reviewed the nature and extent of the persister phenotype in relation to infectious agents affecting women’s health. We show how the quiescent persister microbial phenotype represents the next significant issue that could compromise successful antibiotic therapy. A brief history of antimicrobial therapy is provided as context for the problem posed by the persister phenotype. This review has been focused on the current literature having relevance for physicians concerned with women’s health. The study of this phenotype has led to increasing understanding of the molecular mechanisms for this state which also provides ideas for rational development of drug candidates to interdict these organisms in human disease and explores the possibility of developing specifically targeted molecules to address persisters, research on screening botanicals, existing drugs and chemicals to discover novel approaches to the clinical consequence of microbial persisters. Of interest in this review, is the return to naturally occurring botanical substances, first to be used as anti-infectives, now being considered as possible agents to address persister microorganisms. Overall this paper aims to provide information tailored especially to the obstetrics and gynecology specialists.

Effects of Farnesol on Drug-Resistant and Non-Resistant <i>Candida albicans</i>: Implications for Cosmetic and Pharmaceutical Applications

Background: Farnesol is added to numerous consumer products that intentionally, or inadvertently come in contact with tissues that may harbor the opportunistic yeast, Candida albicans. Objective: This study explores biological consequences of the exposure of Candida albicans from community infections or from a panel of antifungal drug resistant organisms on growth and survival of these organisms when exposed to farnesol. Methods: ATCC supplied Candida albicans from the MP8 drug resistance panel and an additional 12 strains of community-acquired Candida albicans were cultured in the presence of farnesol. With standard micobiologic techniques and flow cytometry evaluation, a series of experiments considered growth, morphology, viability and entrance into the quiescent persister phenotype of Candida with emphasis on differences between drug resistant and community organisms. Results: Differences growth yield, relative cell size and heat susceptibility distinguished the community organisms from the drug-resistant organisms. Using a subset of these organisms, exposure to farnesol resulted in diminished growth, inhibited hyphal growth, diminished cell membrane integrity and increased heat stress susceptibility. Data provided suggest that exposure to farnesol pushes cultures of Candida albicans toward the quiescent persister phenotype. Conclusion: Exposure of drug resistant and community strains of Candida albicans are modestly affected by farnesol in ways that may lessen their pathogenic potential. In contrast, the tendency of farnesol to engender greater numbers of quiescent organisms could support persistence of Candida.