This book succeeds Review of Medical Pharmacology , by Meyers, Jawetz, and Goldfien. Edited by B. G. Katzung, some of the important areas covered include drug receptors and pharmacodynamics, pharmacokinetics of absorption and biotransformation of drugs, autonomic pharmacology of cholinergic and adrenergic receptor stimulants and antagonists, antihypertensive agents, cardiac glycosides and other agents used in the treatment of congestive heart failure, therapeutic drugs for cardiac arrhythmias, diuretics, pharmacology of the CNS drugs such as anticonvulsants and anesthetics, antidepressants, narcotic analgesics, nonsteroidal anti-inflammatory agents, endocrine pharmacology, antimicrobial and antimycobacterial drugs, antiprotozoal and antihelmintic drugs, cancer chemotherapy, and drugs and the immune system. Written by several prominent researchers and scientists, each chapter begins with a section on the basic pharmacology, chemistry, pharmacokinetics, and pharmacodynamics of the agents under discussion. This is followed by a section on clinical pharmacology, which deals with relevant information regarding the clinical use of drugs on the various

Basic and Clinical Pharmacology

Flavonoids are one of the largest classes of small molecular secondary metabolites produced in different parts of the plant. They display a wide range of pharmacological and beneficial health effects for humans, which include, among others, antioxidative activity, free radical scavenging capacity, coronary heart disease prevention and antiatherosclerotic, hepatoprotective, anti-inflammatory, and anticancer activities. Hence, flavonoids are gaining high attention from the pharmaceutical and healthcare industries. Notably, plants synthesize flavonoids in response to microbial infection, and these compounds have been found to be a potent antimicrobial agent against a wide range of pathogenic microorganisms in vitro. Antimicrobial action of flavonoids results from their various biological activities, which may not seem very specific at first. There are, however, promising antibacterial flavonoids that are able not only to selectively target bacterial cells, but also to inhibit virulence factors, as well as other forms of microbial threats, e.g. biofilm formation. Moreover, some plant flavonoids manifest ability to reverse the antibiotic resistance and enhance action of the current antibiotic drugs. Hence, the development and application of flavonoid-based drugs could be a promising approach for antibiotic-resistant infections. This review aims to improve our understanding of the biological and molecular roles of plant flavonoids, focusing mostly on their antimicrobial activities.

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Comprehensive review of antimicrobial activities of plant flavonoids

Urinary tract infections (UTIs) are one of the most common pathological conditions in both community and hospital settings. It has been estimated that about 150 million people worldwide develop UTI each year, with high social costs in terms of hospitalizations and medical expenses. Among the common uropathogens associated to UTIs development, UroPathogenic Escherichia coli (UPEC) is the primary cause. UPEC strains possess a plethora of both structural (as fimbriae, pili, curli, flagella) and secreted (toxins, iron-acquisition systems) virulence factors that contribute to their capacity to cause disease, although the ability to adhere to host epithelial cells in the urinary tract represents the most important determinant of pathogenicity. On the opposite side, the bladder epithelium shows a multifaceted array of host defenses including the urine flow and the secretion of antimicrobial substances, which represent useful tools to counteract bacterial infections. The fascinating and intricate dynamics between these players determine a complex interaction system that needs to be revealed. This review will focus on the most relevant components of UPEC arsenal of pathogenicity together with the major host responses to infection, the current approved treatment and the emergence of resistant UPEC strains, the vaccine strategies, the natural antimicrobial compounds along with innovative anti-adhesive and prophylactic approaches to prevent UTIs.

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UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies.

Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.

Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

Green tea is a popular drink, especially in Asian countries, although its popularity continues to spread across the globe. The health benefits of green tea, derived from the leaves of the Camellia sinensis plant, have been studied for many years. Fairly recently, researchers have begun to look at the possibility of using green tea in antimicrobial therapy, and the potential prevention of infections. The particular properties of catechins found in the tea have shown promise for having antimicrobial effects. There are four main catechins (polyphenols) found in green tea: (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG). Three of these, ECG, EGC, and EGCG have been shown to have antimicrobial effects against a variety of organisms. These catechins have exhibited a variety of antimicrobial mechanisms. The results of studies on the antimicrobial effects of green tea have shown that the potential for preventive and therapeutic purposes is present. Further data collection on studies performed with human consumption during the course of infections, and studies on the occurrence of infections in populations that consume regular amounts of green tea will be necessary to complete the picture of its antimicrobial possibilities.

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The antimicrobial possibilities of green tea

Resistance to antimicrobial agents has become a major source of morbidity and mortality worldwide. When antibiotics were first introduced in the 1900's, it was thought that we had won the war against microorganisms. It was soon discovered however, that the microorganisms were capable of developing resistance to any of the drugs that were used. Apparently most pathogenic microorganisms have the capability of developing resistance to at least some antimicrobial agents. The main mechanisms of resistance are: limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. These mechanisms may be native to the microorganisms, or acquired from other microorganisms. Understanding more about these mechanisms should hopefully lead to better treatment options for infective diseases, and development of antimicrobial drugs that can withstand the microorganisms attempts to become resistant.

An overview of the antimicrobial resistance mechanisms of bacteria

Green tea is one of the most popular drinks consumed worldwide. Produced mainly in Asian countries from the leaves of the Camellia sinensis plant, the potential health benefits have been widely studied. Recently, researchers have studied the ability of green tea to eradicate infectious agents and the ability to actually prevent infections. The important components in green tea that show antimicrobial properties are the catechins. The four main catechins that occur in green tea are (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG). Of these catechins, EGCG and EGC are found in the highest amounts in green tea and have been the subject of most of the studies. These catechins have been shown to demonstrate a variety of antimicrobial properties, both to organisms affected and in mechanisms used. Consumption of green tea has been shown to distribute these compounds and/or their metabolites throughout the body, which allows for not only the possibility of treatment of infections but also the prevention of infections.

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Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases.

Background: Urinary tract infections (UTIs) are a very most common type of infection worldwide, and result in billions of dollars in medical care costs. Escherichia coli is the infective agent for 80%-90% of all UTIs. Green tea, derived from leaves of the Camellia sinensis plant has been shown to have various potential health benefits (e.g. cardiovascular disease and cancer). The major beneficial components of green tea have been characterized, and are now known to be polyphenolic catechins. The main catechins in green tea are (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC), (-)-epicatechin (EC), and (-)-epigallocatechin-3-gallate (EGCG). EGCG and EGC have been shown to have antimicrobial effects, but only EGC has been shown to be excreted in urine. Isolates of E. coli from urinary tract infections collected between 2007-2008 were characterized for antimicrobial resistance to standard drugs. Then 80 of these isolates, representing a wide spectrum of antimicrobial susceptibility patterns, were selected for testing using an extract of green tea. Results: The concentrations of green tea extract tested were 0, 2.5, 3.0, 3.5, and 4.0 mg/ml. All of the strains tested, except one, had MICs of ≤4.0 mg/ml, with 40% of the isolates having an MIC of ≤2.5 mg/ml, 36% of the isolates having an MIC of ≤3.0 mg/ml, 18% of the isolates having an MIC of ≤3.5 mg/ml, and 5% of the isolates having an MIC of ≤4.0 mg/ml. Two control strains varied in susceptibility, one having an MIC of ≤2.5 mg/ml, another having an MIC of ≤3.5 mg/ml, and the third having an MIC of ≤4.0 mg/ml. Conclusion: Since EGC has been shown to have antimicrobial effects on E. coli, and EGC has been shown to be excreted in the urine in a high enough concentration to potentially be effective as an antimicrobial; these MIC results suggest that ingesting green tea could have potential antimicrobial effects on urinary tract infections caused by E. coli.

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Green tea as an effective antimicrobial for urinary tract infections caused by Escherichia coli.

Complicated intra-abdominal and skin and skin structure infections are widely varied in presentation. These infections very often lead to an increase in length of hospital stay, with a resulting increase in costs and mortality. In addition, these infections may be caused by a wide variety of bacteria and are often polymicrobial with the possibility of the presence of antimicrobial-resistant strains, such as methicillin-resistant Staphylococcus aureus, vancomycin- resistant enterococci, extended-spectrum β-lactamase strains (Escherichia coli, Klebsiella pneu- moniae), and K. pneumoniae carbapenemase-producing strains. In combination with patients' immunosuppression or comorbidities, the treatment and management options for initial therapy success are few. Tigecycline, a new glycylcyline antimicrobial from the tetracycline drug class, represents a viable option for the successful treatment of these infections. It has been shown to have activity against a wide variety of bacteria, including the antimicrobial-resistant strains. As with all tetracycline drugs, it is not recommended for pregnant or nursing women. The potential side effects are those typical of tetracycline drugs: nausea, vomiting, and headaches. Drug-drug interactions are not expected, and renal function monitoring is not necessary.

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Antibiotic optimization in the difficult-to-treat patient with complicated intra-abdominal or complicated skin and skin structure infections: focus on tigecycline.

Wanda C. Reygaert

Papers

An overview of the antimicrobial resistance mechanisms of bacteria

The antimicrobial possibilities of green tea

Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases.

Green tea as an effective antimicrobial for urinary tract infections caused by Escherichia coli.

Antibiotic optimization in the difficult-to-treat patient with complicated intra-abdominal or complicated skin and skin structure infections: focus on tigecycline.