Polymyxin Antibiotics From Laboratory Bench To Bedside

This volume is the first-ever complete treatise on polymyxins and presents the most comprehensive and up-to-date reviews of all major research and clinical topics from chemistry, microbiology, pharmacology, clinical use, to drug discovery. All chapters were written by internationally leading researchers and clinicians in the field. It is our wish that readers discover the importance of polymyxin structure in relation to the mechanisms of activity, resistance and toxicity. We emphasized that reliable analytic methods for polymyxins are critical when investigating their pharmacokinetics (PK) and pharmacodynamics (PD). The complicated dose definitions and different pharmacopoeial standards have already compromised the safe use of polymyxins in patients. Therefore, informed by the latest pharmacological information, scientifically-based dosing recommendations have been proposed for intravenous polymyxins. Considering the PK/PD limitations and potential development of resistance, polymyxin combinations are encouraged; however, the current literature has not shown definite microbiological benefits, possibly because most clinical studies to date overlooked key PK/PD principles. Nephrotoxicity is the major dose-limiting factor and it is imperative to elucidate the mechanisms and develop novel approaches to minimize polymyxin-associated toxicities. In addition, the anti-endotoxin effect of polymyxins supports their clinical use to treat Gram-negative sepsis. Fortunately, the discovery of new-generation polymyxins with wider therapeutic windows has benefited from the latest achievements in polymyxin research. This book provides extensive pharmacological information on polymyxins to infectious diseases clinicians, pharmacists, clinical microbiologists, antimicrobial pharmacologists, and pharmaceutical scientists, and is an essential read for those who aim to develop novel polymyxins and improve their clinical use as a last-line defense against Gram-negative ‘superbugs’.

Antimicrobial resistance (AMR) is a global public health threat that needs immediate attention and action from the scientific community. This book compiles and presents the latest and most important aspects of AMR, including the biology involved, its persistence and spread, and novel approaches to tackle this threat. The book first describes the mechanisms and spread of AMR, and then discusses the various approaches and strategies for combating it. Important topics include, microbial pathogenesis, AMR traits and major mechanisms underlying drug-resistance and the emerging strategies and technologies for combating AMR. Emphasis has been given on current developments about natural products including potent phyto-molecules, antimicrobial peptides and endophytes effective against the drug-resistant microbes and target the main drug-resistance determinants (efflux pumps, biofilms, quorum sensing, plasmids, etc.) in these bacterial pathogens. Other exciting topics include applications of nanomaterials in tackling AMR and CRISPR-Cas based precise sequence-specific antimicrobials. This informative book is meant for students and researchers in basic and medical microbiology and biotechnology. It is also useful to public health professionals and industry experts involved in AMR research and related drug-designing.

There is a growing interest in unmet needs for the development of a new discipline in drug discovery and in university education on polypharmacology. However, there has not been a book with the comprehensive compilation of basic knowledge and advanced methodology that is needed. This book aims to meet the needs making Polypharmacology a new sub-discipline of Pharmacology, not only being a hot area of pharmacological research and education but also a new paradigm for drug discovery. It contains the contents covering the entire scope of Polypharmacology including systemic in-depth exposition of basic knowledge, novel concepts, innovative technologies, and translational and clinical applications by showcasing state-of-the-art strategies and step-by-step instructions of cutting-edge methods. The contents of this book targets broad readerships including scientists in pharmacology research and drug development, and university teachers and graduates in medical school or school of pharmacy.

Translational medicine addresses the gap between research and the clinical application of new discoveries. To efficiently deliver new drugs to care centers, a preclinical evaluation, both in vitro and in vivo, is required to ensure that the most active and least toxic compounds are selected as well as to predict clinical outcome. Antimicrobial nanomedicines have been shown to have higher specificity in their therapeutic targets and the ability to serve as adjuvants, increasing the effectiveness of pre-existing immune compounds. The design and development of new standardized protocols for evaluating antimicrobial nanomedicines is needed for both the industry and clinical laboratory. These protocols must aim to evaluate laboratory activity and present models of pharmacokinetic-pharmacodynamic and toxicokinetic behavior that predict absorption and distribution. Likewise, these protocols must follow a theranostics approach, be able to detect promising formulations, diagnose the infectious disease, and determine the correct treatment to implement a personalized therapeutic behavior. Given the possibilities that nanotechnology offers, not updating to new screening platforms is inadequate as it prevents the correct application of discoveries, increasing the effect of the valley of death between innovations and their use. This book is structured to discuss the fundamentals taken into account for the design of robust, reproducible and automatable evaluation platforms. These vital platforms should enable the discovery of new medicines with which to face antimicrobial resistance (RAM), one of the great problems of our time.

The Latin American region has been at the forefront in combating infections caused by Escherichia coli strains in humans, animals, and the environment. The continuous emergence and evolution of pathogenic E. coli strains associated with human and animal infections have demonstrated that (i) groups of related pathogenic E. coli are responsible for most infections caused by this bacterial species; (ii) diverse virulence phenotypes expressed during infection defined each one of these pathogroups; (iii) the geographical distribution of pathogroups in Latin America and the evolution of new isolates was defined by the dominant pathogroup and presence of distinct virulence strains; (iv) acquisition of mobile elements or accumulation of point mutations accelerate the development of antibiotic resistance in some of these strains. The Latin American Coalition for Escherichia coli Research (LACER), a multidisciplinary network of over seventy research groups in eleven Latin American countries and the USA, was established in 2009 to apply One Health principles in defining and combating this pathogen. The previous edition of this text, Escherichia coli in the Americas (c. 2016) was the culmination of their wisdom about E. coli, from its role as a commensal bacterium to its characteristics as a pathogen causing disease in animals and humans. This new edition presents recent advances and contextualizes all aspects of E. coli in a One Health perspective, from the environment, to animals, to humans. It addresses E. coli interactions with host microbiota, CNS, and phages. It includes cutting edge insights on hybrid strains, molecular mechanisms of virulence and pathogenesis, resistance, domestic and wild reservoirs, disease surveillance in Latin America, genomic analysis, food safety, and new therapies. Crucially, it also provides translations and analysis of key reports on Escherichia coli published in Spanish and Portuguese. This book serves as a critical resource for scientists in industry and academia, clinicians managing associated infections, and trainees and students studying basic and clinical aspects of E. coli pathogenesis.

The lungs are the organ for gas exchange between the body and the external environment. Dysfunction of upper airway epithelium and smooth muscle cells leads to pathogenesis of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and other conditions, resulting in airway inflammation and narrowing. Injury to alveolar epithelium and endothelium causes influx of neutrophil and protein-rich fluid from circulation, resulting in edema and disruption of gas exchange. In addition to lung structural cells, immune cells, including alveolar macrophages and lymphocytes play critical roles in the maintenance of lung function. This book contributes to the understanding homeostasis of lung cells in the physiological and pathological conditions critical to the development of novel therapeutics. Key Features Highlights the role the lungs play as an interface between the body and the environment Describes the underlying mechanism of lung diseases Emphasizes the ways nutrition contributes to lung health as well as the ways pollution adversely affect lung function Includes contributions from leading researchers Chapters 8 and 13 of this book are available for free in PDF format as Open Access from the individual product page at www.routledge.com. It has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license.

The need for state-of-the-art antimicrobial agents is greater than ever because of the development of multidrug resistance in communal pathogens, the rapid rise of new infections, and the potential for use of multidrug-resistant agents in biological protection. Although the need for novel antimicrobials is increasing, the development of such agents faces significant obstacles. Pharmaceutical research and development costs are estimated to be $400–$800 million per approved agent. The most important natural antimicrobial compounds derived from various plant sources containing a wide variety of secondary metabolites. With collected contributions from international subject experts, this volume focuses primarily on antimicrobials. This book deliberates recent developments in microbial science in combating infectious diseases and explores advances in antimicrobial constituents and their applications in the fight against bacteria. In addition, it also provides a variety of photographs, diagrams, and tables to help illustrate the material. The novel strategies to combat antimicrobial resistance are also described, emphasizing collaborative measures of control. We describe the concerted efforts undertaken by global communities to combat antimicrobial resistance in detail. The most efficient strategy could be a behavioural change towards indiscriminate consumption, usage, and prescription of antibiotics. Students, research scientists, academicians and policy makers can benefit from Antimicrobials in Pharmaceutical and Medicinal Research as a resource that addresses biotechnology, applied microbiology, healthcare/pharmaceutical products, medicinal plant products, and all disciplines related to antimicrobial research. Features of the book: Covers development in plant-based antimicrobials for sepsis management and progress Describes modern approaches for phyto-nanoconjugates in combating multidrug resistance in biomedicine Details methods to improve antimicrobial properties to have a longer service life in combating infection Describe bacteriocins and plant metabolites as biotechnological tools in food, pharmaceuticals and therapeutics applications Highlights natural antimicrobial therapeutic peptides Offers current and future applications of emerging antimicrobial technologies

Section 1 - General Critical Care Section 2 - Respiratory Critical Care Section 3 - Hepatic, Gastrointestinal & Endocrine Emergencies in ICU Section 4 - Neuro Critical Care Section 5 - Nephro Critical Care Section 6- Infections & Antibiotics Section 7- Obstetric Critical Care Section 8 - Trauma Critical Care Section 9 - Cardiac Critical Care Section 10- Poisoning Section 11- Onco Critical care