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This book covers intentional design aspects for combinations of drugs, single-molecule hybrids with potential or actual multiple actions, pro-drugs which could yield multiple activity outcomes, and future possibilities. The approach of the book is interdisciplinary, and it provides greater understanding of the complex interplay of factors involved in the medicinal chemistry design and laboratory development of multiply active antibacterials. The scope of the book appeals to readers who are researching in the field of antibacterials using the approach of medicinal chemistry design and drug development.
This book covers intentional design aspects for combinations of drugs, single-molecule hybrids with potential or actual multiple actions, pro-drugs which could yield multiple activity outcomes, and future possibilities. The approach of the book is interdisciplinary, and it provides greater understanding of the complex interplay of factors involved in the medicinal chemistry design and laboratory development of multiply active antibacterials. The scope of the book appeals to readers who are researching in the field of antibacterials using the approach of medicinal chemistry design and drug development. .
Why Antibiotic Resistance? The use of antibiotics in human and veterinary medicine may have consequences beyond their intended applications. The “One Health” concept recognizes that the health of humans is connected to the health of animals and the environment. Progress in molecular genetics is facilitating the rapid evaluation of the essentiality of these targets on a genomic scale. In 2015, a group of researchers established the International Conference on Antibiotic Resistance (IC2AR).The primary objective of this meeting is to bring together scientists involved in antibiotic resistance prevention and control. The IC2AR conducted its inaugural world congress in January 2015 at Caparica (Portugal). Antimicrobial resistance presents a significant challenge to scientists in the field of infectious diseases. The full knowledge of how antibiotics resistance is evolving and being transmitted between hosts in different ecosystems is taking on great importance. Necessary action includes research to define the scope of the problem including its various sources. This eBook comprises a series of original research and review articles dealing with the epidemiology of resistance in animal and zoonotic pathogens, mobile elements containing resistance genes, the omics of antimicrobial resistance, emerging antimicrobial resistance mechanisms, control of resistant infections, establishing antimicrobial use and resistance surveillance systems, and alternatives strategies to overcome the problem of antimicrobial resistance worldwide. Gilberto Igrejas, José Luis Capelo and Patrícia Poeta Scientific Committee of IC2AR, February 20th, 2017
Over the past decade, genome sequencing projects and the associated efforts have facilitated the discovery of several novel disease targets and the approval of several innovative drugs. To further exploit this data for human health and disease, there is a need to understand the genome data itself in detail, discover novel targets, understand their role in physiological pathways and associated diseases, with the aim to translate these discoveries to clinical and preventive medicine. It is equally important to understand the labors and limitations in integrating clinical phenotypes with genomic, transcriptomic, proteomic and metabolomic approaches. T
Historically, the first observation of a transmissible lytic agent that is specifically active against a bacterium (Bacillus anthracis) was by a Russian microbiologist Nikolay Gamaleya in 1898. At that time, however, it was too early to make a connection to another discovery made by Dmitri Ivanovsky in 1892 and Martinus Beijerinck in 1898 on a non-bacterial pathogen infecting tobacco plants. Thus the viral world was discovered in two of the three domains of life, and our current understanding is that viruses represent the most abundant biological entities on the planet. The potential of bacteriophages for infection treatment have been recognized after the discoveries by Frederick Twort and Felix d’Hérelle in 1915 and 1917. Subsequent phage therapy developments, however, have been overshadowed by the remarkable success of antibiotics in infection control and treatment, and phage therapy research and development persisted mostly in the former Soviet Union countries, Russia and Georgia, as well as in France and Poland. The dramatic rise of antibiotic resistance and especially of multi-drug resistance among human and animal bacterial pathogens, however, challenged the position of antibiotics as a single most important pillar for infection control and treatment. Thus there is a renewed interest in phage therapy as a possible additive/alternative therapy, especially for the infections that resist routine antibiotic treatment. The basis for the revival of phage therapy is affected by a number of issues that need to be resolved before it can enter the arena, which is traditionally reserved for antibiotics. Probably the most important is the regulatory issue: How should phage therapy be regulated? Similarly to drugs? Then the co-evolving nature of phage-bacterial host relationship will be a major hurdle for the production of consistent phage formulae. Or should we resort to the phage products such as lysins and the corresponding engineered versions in order to have accurate and consistent delivery doses? We still have very limited knowledge about the pharmacodynamics of phage therapy. More data, obtained in animal models, are necessary to evaluate the phage therapy efficiency compared, for example, to antibiotics. Another aspect is the safety of phage therapy. How do phages interact with the immune system and to what costs, or benefits? What are the risks, in the course of phage therapy, of transduction of undesirable properties such as virulence or antibiotic resistance genes? How frequent is the development of bacterial host resistance during phage therapy? Understanding these and many other aspects of phage therapy, basic and applied, is the main subject of this Topic.
Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.
New drugs are frequently entering into the market along with the existing drugs. The antibacterial agents can be discussed in five major classes, i.e. classification based on the type of action, source, spectrum of activity, chemical structure and function. Resistance of bacteria to antibiotics is an urgent problem of the humanity, which leads us to the lack of therapy for serious bacterial infections. Development of new antibiotics has almost ceased in the last decades - even when a new antibiotic is launched, very soon the resistance of bacteria appears. Industrial textiles exposed as awnings, screens, tents; upholstery used in large public areas such as hospitals, hotels and stations; fabrics for transports; protective clothing and personal protective equipment; bed sheets and blankets; textiles left wet between processing steps; intimate apparel, underwear, socks and sportswear, disinfection of air and water for white rooms, hospitals and operating theatres, food and pharma industries, water depuration, drinkable water supplying and air conditioning systems. Many clinicians recommend alternative approaches to using antimicrobial substances. Moreover, the majority of bioagents demonstrate on antibiotics for treatment of a wide range of diseases in human sectors. However, the misuse and mishandling of drugs lead to microbial, particularly bacterial, resistance as well as result in the difficulty of treating microbial diseases. Hence, the proposed book will give more precise information on novel antibacterial compound(s).
Reports on the emergence and prevalence of resistant bacterial infections in hospitals and communities raise concerns that we may soon no longer be able to rely on antibiotics as a way to control infectious diseases. Effective medical care would require the constant introduction of novel antibiotics to keep up in the “arms race” with resistant pathogens. This book closely examines the latest developments in the field of antibacterial research and development. It starts with an overview of the growing prevalence of resistant Gram-positive and Gram-negative pathogens, including their various resistance mechanisms, prevalence, risk factors and therapeutic options. The focus then shifts to a comprehensive description of all major chemical classes with antibacterial properties, their chemistry, mode of action, and the generation of analogs; information that provides the basis for the design of improved molecules to defeat microbial infections and combat the emerging resistances. In closing, recently developed compounds already in clinical use, those in preclinical or first clinical studies, and a number of promising targets to be exploited in the discovery stage are discussed.