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International Journal of Antimicrobial... Aug 2021The dramatic increase in antimicrobial resistance and the limited pharmacological treatment options highlight the urgent need to optimize therapeutic regimens of new and... (Review)
Review
The dramatic increase in antimicrobial resistance and the limited pharmacological treatment options highlight the urgent need to optimize therapeutic regimens of new and available anti-infectives. Several in-vitro and in-vivo infection models are employed to understand the relationship between drug exposure profiles in plasma or at the site of infection (pharmacokinetics) and the time course of therapeutic response (pharmacodynamics) to select and optimize dosage regimens for new and approved drugs. Well-designed preclinical studies, combined with mathematical-model-based pharmacokinetic/pharmacodynamic analysis and in-silico simulations, are critical for the effective translation of preclinical data and design of appropriate and successful clinical trials. Integration with population pharmacokinetic modelling and simulations allows for the incorporation of interindividual variability that occurs in both pharmacokinetics and pharmacodynamics, and helps to predict the probability of target attainment and treatment outcome in patients. This article reviews the role of pharmacokinetic/pharmacodynamic approaches in the optimization of dosage regimens to maximize antibacterial efficacy while minimizing toxicity and emergence of resistance, and to achieve a high likelihood of therapeutic success. Polymyxin B, an approved drug with a narrow therapeutic window, serves as an illustrative example to highlight the importance of pharmacokinetic/pharmacodynamic modelling in conjunction with experimentation, employing static time-kill studies followed by dynamic in-vitro or in-vivo models, or both, to learn and confirm mechanistic insights necessary for translation to the bedside.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 34058336
DOI: 10.1016/j.ijantimicag.2021.106368 -
Frontiers in Immunology 2022The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections... (Review)
Review
The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development. Antimicrobial peptides from the innate immune system represent one promising class that offers a potential solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive peptides. Improving the therapeutic properties of these peptides is a strategy for reducing the clinical limitations and synthetic mimics of antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlight key and recent development in the field of small antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides; Antimicrobial Peptides; Bacteria
PubMed: 35720375
DOI: 10.3389/fimmu.2022.915368 -
International Journal of Molecular... Sep 2021The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a... (Review)
Review
The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.
Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Antiparasitic Agents; Antiviral Agents; Blood Platelets; Humans; Ribonucleases
PubMed: 34638568
DOI: 10.3390/ijms221910230 -
Annual Review of Medicine Jan 2020HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum... (Review)
Review
HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum have the potential to prevent the sexual acquisition of HIV in women and men. Topical microbicides may meet the prevention needs of individuals and groups for whom oral daily forms of pre-exposure prophylaxis (PrEP) have not been acceptable. Microbicides can provide personal control over HIV prevention and offer the possibility of discreet use, qualities that may be particularly important for receptive partners in sexual relationships such as women and transgender women and men, who together account for the clear majority of new HIV infections worldwide. Although the promise of such a product emerged nearly three decades ago, proof of concept has been demonstrated only within the last decade. A robust pipeline of microbicidal gels, films, inserts, and rings has been evaluated in multiple studies among at-risk women and men, and refinement of products for ease of use, reversibility, and high safety is the priority for the field.
Topics: Adult; Anti-HIV Agents; Anti-Infective Agents, Local; Drug Compounding; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Male; Patient Safety; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Rectum; Sexual Partners; Vagina
PubMed: 31613684
DOI: 10.1146/annurev-med-090518-093731 -
Future Microbiology 2015
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides; Humans
PubMed: 26118303
DOI: 10.2217/fmb.15.45 -
Current Medicinal Chemistry 2015
Topics: Anti-Infective Agents; Communicable Diseases; Drug Discovery
PubMed: 26051412
DOI: 10.2174/0929867322666150608093816 -
Journal of Applied Microbiology Nov 2017Silver has attracted a lot of attention as a powerful, broad spectrum and natural antimicrobial agent since the ancient times because of its nontoxic nature to the human... (Review)
Review
Silver has attracted a lot of attention as a powerful, broad spectrum and natural antimicrobial agent since the ancient times because of its nontoxic nature to the human body at low concentrations. It has been used in treatment of various infections and ulcers, storage of water and prevention of bacterial growth on the surfaces and within materials. However, there are numerous medical and health benefits of colloidal or nanosilver apart from its microbicidal ability which as yet has not been fully embraced by the medical community. These include antiplatelet activity, antioxidant effect, anticancer activity, wound healing and bone regeneration, enhancement of immunity, and increase in antibiotic efficiency. Additionally silver also provides protection against alcohol toxicity, upper respiratory tract infections and stomach ailments. Although nanosilver has been proposed for various topical applications, its usage by ingestion and inhalation remains controversial due to the lack of detailed and precise toxicity information. These beneficial properties of silver can be utilized by using silver at very low concentrations which are not harmful to the human body and environment. The following review discusses the diverse medical applications of silver and further recommends human clinical studies for its in vivo usage.
Topics: Animals; Anti-Infective Agents; Dose-Response Relationship, Drug; Humans; Silver
PubMed: 28650591
DOI: 10.1111/jam.13525 -
Chemistry & Biodiversity Sep 2019The natural polyisoprenylated benzophenone derivatives garcinol and isogarcinol are secondary plant metabolites isolated from various Garcinia species including Garcinia... (Review)
Review
The natural polyisoprenylated benzophenone derivatives garcinol and isogarcinol are secondary plant metabolites isolated from various Garcinia species including Garcinia indica. This review takes stock of the recent chemical and biological research into these interesting natural compounds over the last five years. New biological sources and chemical syntheses are discussed followed by new insights into the activity of garcinol and isogarcinol against cancer, pathogenic bacteria, parasite infections and various inflammatory diseases.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Antiprotozoal Agents; Garcinia; Humans; Neoplasms; Terpenes
PubMed: 31386266
DOI: 10.1002/cbdv.201900366 -
The Journal of Antibiotics Feb 2018The advent of modern antibiotics contributed enormously to the dramatic extension of human lifespan since their discovery by virtue of their lethal and selective action... (Review)
Review
The advent of modern antibiotics contributed enormously to the dramatic extension of human lifespan since their discovery by virtue of their lethal and selective action against pathogenic microbes. And yet despite our powerful arsenal of weapons against these pathogens, the war against them has not been won. And it may never be. Drug resistance is still menacing the society with many lives being lost due to deadly infections caused by continuously evolving strains spread beyond our means to eradicate them or prevent their spreading. Herein, the emergence and evolution of antibiotics is briefly reviewed, and a select number of total syntheses of naturally occurring antibiotics from the authors' laboratories are highlighted. The article concludes with a strong endorsement of the current efforts to intensify our fight against these dangerous pathogens with the hope that, this time, these initiatives will be sufficiently focused and serious enough so as to achieve our set goals of, at least, being prepared and ahead of them as part of our drive to improve humanity's healthcare and wellbeing.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Microbial; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Penicillins
PubMed: 28676714
DOI: 10.1038/ja.2017.62 -
Culture, Health & Sexuality Jun 2020Men desire to be involved in their partner's decision-making about vaginal microbicide use. This coincides with women's desire to inform male partners about their...
Men desire to be involved in their partner's decision-making about vaginal microbicide use. This coincides with women's desire to inform male partners about their microbicide use. Educating men about microbicides may enhance acceptability and generate critical support for the female participants of microbicide trials. In this multiphase mixed-methods study, we adapted an educational intervention on vaginal microbicides and tested it among men (n = 45) to determine its effect on men's knowledge regarding HIV/STI, vaginal microbicides and microbicide trials. We also conducted focus group discussions (FGDs) with the female partners (K = 3, n = 43) of the study participants and community representatives (K = 2, n = 24) to obtain their views on male partner microbicide education. We analysed FGD data for key themes using content analysis. HIV and vaginal microbicide knowledge scores increased significantly among men after the educational intervention. Both women and men highly supported male partner microbicide education, in the context of existing gender relations, to increase men's understanding about microbicides, promote adherence and help women gain their partners' trust. Complex gender dynamics should be considered when designing male partner educational interventions to improve acceptability and the use of microbicides and other female-initiated HIV prevention methods.
Topics: Administration, Intravaginal; Adult; Anti-Infective Agents; Anti-Infective Agents, Local; Contraception Behavior; Female; HIV Infections; Health Education; Humans; Kenya; Male; Sexual Partners; Sexually Transmitted Diseases; Surveys and Questionnaires; Vaginal Creams, Foams, and Jellies
PubMed: 31241426
DOI: 10.1080/13691058.2019.1627583